Bibliography

Single-walled carbon nanotubes as anisotropic relaxation probes for magnetic resonance imaging

Arisbel Cerpa, Mariana Köber, Daniel Calle, Viviana Negri, Jose María Gavira, Antonio Hernanz, Fernando Briones, Sebastián Cerdán, Paloma Ballesteros

ABSTRACT: We report on the preparation and characterization of magnetically oriented single-walled carbon nanotube arrangements as novel nanoprobes to enhance anisotropically water relaxation as detected by magnetic resonance imaging methods. SWCNT suspensions immobilized in agarose gels showed evident magnetic anisotropy with significantly longer T2 in the parallel than in the perpendicular orientations.

Medicinal Chemistry Communication 03/2013; 4(4):669-672. · 2.63 Impact Factor

 

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Hypothalamic metabolic compartmentation during appetite regulation as revealed by magnetic resonance imaging and spectroscopy methods.

Blanca Lizarbe, Ania Benitez, Gerardo A Peláez Brioso, Manuel Sánchez-Montañés, Pilar López-Larrubia, Paloma Ballesteros,Sebastián Cerdán

ABSTRACT: We review the role of neuroglial compartmentation and transcellular neurotransmitter cycling during hypothalamic appetite regulation as detected by Magnetic Resonance Imaging (MRI) and Spectroscopy (MRS) methods. We address first the neurochemical basis of neuroendocrine regulation in the hypothalamus and the orexigenic and anorexigenic feed-back loops that control appetite. Then we examine the main MRI and MRS strategies that have been used to investigate appetite regulation. Manganese-enhanced magnetic resonance imaging (MEMRI), Blood oxygenation level-dependent contrast (BOLD), and Diffusion-weighted magnetic resonance imaging (DWI) have revealed Mn(2+) accumulations, augmented oxygen consumptions, and astrocytic swelling in the hypothalamus under fasting conditions, respectively. High field (1)H magnetic resonance in vivo, showed increased hypothalamic myo-inositol concentrations as compared to other cerebral structures. (1)H and (13)C high resolution magic angle spinning (HRMAS) revealed increased neuroglial oxidative and glycolytic metabolism, as well as increased hypothalamic glutamatergic and GABAergic neurotransmissions under orexigenic stimulation. We propose here an integrative interpretation of all these findings suggesting that the neuroendocrine regulation of appetite is supported by important ionic and metabolic transcellular fluxes which begin at the tripartite orexigenic clefts and become extended spatially in the hypothalamus through astrocytic networks becoming eventually MRI and MRS detectable.

Frontiers in Neuroenergetics 01/2013; 5:6.

TiagoB. Rodrigues, Alejandra Sierra, Paloma Ballesteros,Sebastián Cerdán

Neural Metabolism In Vivo, Edited by In-Young Choi, Rolf Gruetter, 01/2012: chapter 24: pages 715-753; Springer US., ISBN: 9781461417873

Francisco Fernández-Trillo, Jesús Pacheco-Torres, Juan Correa, Paloma Ballesteros, Pilar Lopez-Larrubia, Sebastián Cerdán,Ricardo Riguera, Eduardo Fernandez-Megia

ABSTRACT: The Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC) allows the efficient and complete functionalization of dendrimers with preformed Gd chelates (prelabeling) to give monodisperse macromolecular contrast agents (CAs) for magnetic resonance imaging (MRI). This monodispersity contrasts with the typical distribution of materials obtained by classical routes and facilitates the characterization and quality control demanded for clinical applications. The potential of a new family of PEG-dendritic CA based on a gallic acid-triethylene glycol (GATG) core functionalized with up to 27 Gd complexes has been explored in vitro and in vivo, showing contrast enhancements similar to those of Gadomer-17, which reveals them to be a promising platform for the development of CA for MRI.

Biomacromolecules 08/2011; 12(8):2902-7. · 5.79 Impact Factor

Jesús Pacheco-Torres, Pilar López-Larrubia, Paloma Ballesteros,Sebastián Cerdán

ABSTRACT: Tumor hypoxia results from the negative balance between the oxygen demands of the tissue and the capacity of the neovasculature to deliver sufficient oxygen. The resulting oxygen deficit has important consequences with regard to the aggressiveness and malignancy of tumors, as well as their resistance to therapy, endowing the imaging of hypoxia with vital repercussions in tumor prognosis and therapy design. The molecular and cellular events underlying hypoxia are mediated mainly through hypoxia-inducible factor, a transcription factor with pleiotropic effects over a variety of cellular processes, including oncologic transformation, invasion and metastasis. However, few methodologies have been able to monitor noninvasively the oxygen tensions in vivo. MRI and MRS are often used for this purpose. Most MRI approaches are based on the effects of the local oxygen tension on: (i) the relaxation times of (19)F or (1)H indicators, such as perfluorocarbons or their (1)H analogs; (ii) the hemodynamics and magnetic susceptibility effects of oxy- and deoxyhemoglobin; and (iii) the effects of paramagnetic oxygen on the relaxation times of tissue water. (19)F MRS approaches monitor tumor hypoxia through the selective accumulation of reduced nitroimidazole derivatives in hypoxic zones, whereas electron spin resonance methods determine the oxygen level through its influence on the linewidths of appropriate paramagnetic probes in vivo. Finally, Overhauser-enhanced MRI combines the sensitivity of EPR methodology with the resolution of MRI, providing a window into the future use of hyperpolarized oxygen probes.

NMR in Biomedicine 01/2011; 24(1):1-16. · 3.56 Impact Factor

 

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Polymorphism of racemic imidazol-1-ylsuccinic acid derivatives. Suitable probes for extracellular pH by magnetic resonance spectroscopic imaging

Carmen Ubide-Barreda, Mª Luisa Rojas, Pedro José Martínez de Paz, Valeria Righi, Paloma Ballesteros

ABSTRACT: The polymorphism of racemic imidazol-1ylsuccinic acid derivatives, a series of compounds previously used as extracellular pH probes for NMR spectroscopy, is investigated by crystallization in different solvents. The mono-ester, (±)-3-(ethoxycarbonyl)-2-(imidazol-1-yl) propionic acid, shows two different polymorphs when recrystallized in absolute ethanol (Form I) or water (Form II), respectively. These two forms have been characterized by optical microscopy, powder X-ray diffraction analysis, and thermogravimetry. Polymorphs I and II can also be distinguished by solid state CP-MAS 13C NMR spectroscopy

ARKIVOC: archive for organic chemistry 01/2011; 2011(iii):179-190. · 1.08 Impact Factor

 

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Environmentally sensitive paramagnetic and diamagnetic contrast agents for nuclear magnetic resonance imaging and spectroscopy.

Jesus Pacheco-Torres, Daniel Calle, Blanca Lizarbe, Viviana Negri, Carmen Ubide, Rosa Fayos, Pilar López Larrubia, Paloma Ballesteros, Sebastian Cerdan

ABSTRACT: Even though alterations in the microenvironmental properties of tissues underlie the development of the most prevalent and morbid pathologies, they are not directly observable in vivo by Magnetic Resonance Imaging (MRI) or Spectroscopy (MRS) methods. This circumstance has lead to the development of a wide variety of exogenous paramagnetic and diamagnetic MRI and MRS probes able to inform non invasively on microenvironmental variables such as pH, pO(2), ion concentration o even temperature. This review covers the fundamentals of environmental contrast and the current arsenal of endogenous and exogenous MRI and MRS contrast enhancing agents available to visualize it. We begin describing the physicochemical background necessary to understand paramagnetic and diamagnetic contrast enhancement with a special reference to novel magnetization transfer and (13)C hyperpolarization strategies. We describe then the main macrocyclic structures used to support the environmentally sensitive paramagnetic sensors, including CEST and PARACEST pH sensitive probes, temperature probes and enzyme activity or gene expression activatable probes. Finally we address the most commonly used diamagnetic contrast agents including imidazolic derivatives to reveal extracellular pH and tissue pO(2) values by MRS. The potential applications of these agents in multimodal and molecular imaging approaches are discussed.

Current topics in medicinal chemistry 01/2011; 11(1):115-30. · 4.47 Impact Factor

 

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Environmentally Sensitive Paramagnetic and Diamagnetic Contrast Agents for Nuclear Magnetic Resonance Imaging and Spectroscopy

Jesus Pacheco-Torres, Daniel Calle, Blanca Lizarbe, Viviana Negri, Carmen Ubide, Rosa Fayos, Pilar Lopez Larrubia, Paloma Ballesteros, Sebastian Cerdan

ABSTRACT: Even though alterations in the microenvironmental properties of tissues underlie the development of the most prevalent and morbid pathologies, they are not directly observable in vivo by Magnetic Resonance Imaging (MRI) or Spectroscopy (MRS) methods. This circumstance has lead to the development of a wide variety of exogenous paramagnetic and diamagnetic MRI and MRS probes able to inform non invasively on microenvironmental variables such as pH, pO2, ion concentration o even temperature. This review covers the fundamentals of environmental contrast and the current arsenal of endogenous and exogenous MRI and MRS contrast enhancing agents available to visualize it. We begin describing the physicochemical background necessary to understand paramagnetic and diamagnetic contrast enhancement with a special reference to novel magnetization transfer and 13C hiperpolarization strategies. We describe then the main macrocyclic structures used to support the environmentally sensitive paramagnetic sensors, including CEST and PARACEST pH sensitive probes, temperature probes and enzyme activity or gene expression activatable probes. Finally we address the most commonly used diamagnetic contrast agents including imidazolic derivatives to reveal extracellular pH and tissue pO2 values by MRS. The potential applications of these agents in mutimodal and molecular imaging approaches are discussed.

Current Topics in Medicinal Chemistry 12/2010; 11(1):115-130. · 3.45 Impact Factor

 

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Nanotubular paramagnetic probes as contrast agents for magnetic resonance imaging based on the diffusion tensor.

Viviana Negri, Arisbel Cerpa, Pilar López-Larrubia, Laura Nieto-Charques, Sebastián Cerdán, Paloma Ballesteros

ABSTRACT: Introduction Enhanced MRI contrast has been classically induced by reducing the T 1 or T 2 relaxation rates of tissue water either through the administration of the paramagnetic complexes of DTPA or DOTA derivatives or superparamagnetic particles (1-3) . More recently, the non invasive imaging of the Apparent Translational Diffusion Coefficient (ADC) of water molecules and its anisotropic orientation has been shown to provide comprehensive information on tissue microstructure and its pathologiess. [4,5] However, no appropriate exogenous molecules have been designed to improve ADC contrast. An important potential exists, therefore, to increase the information content of ADC weighted Images through the use of contrast agents modifying selectively the ADC properties of tissue water. In this communication, we provide the proof of concept for this novel approach demonstrating that exogenous paramagnetic nanotubular structures induce anisotropic water diffusion detectable by MRI methods. Materials and Methods Commercial Single Walled Carbon Nanotubes (SWNTs:2-10 nm diameter, 1-5 m length) produced by Chemical Vapor Depoasition (CVD) and containing paramagnetic metals (% weight); Ni (17) and Y (4); were oxidized with nitric acid for 48 h and resuspended in an aqueous solution of 2% sodium dodecylbenzene sulphonate (2 mg/mL). Transmission Electron Microscopy (300 kilovols) revealed a average length of 100-200 nm (Figure 2). Axial diffusion weighted images across a 2,5 ml plastic syringe containing the suspension, were acquired with a Bruker Pharmascan spectrometer (horizontal magnet 7.0 Tesla/16 cm diameter) using the diffusion weighted spin-echo imaging sequence (matrix size = 256 x 256, TR = 500 ms, TE = 10,6 ms; section width = 1mm, Number of averages = 3, Field of view = 3,8 x 3,8 cm, Diffusion time D= 20 ms and diffusion gradient duration d=4 ms) equipped with an Echo Planar Imaging (EPI) readout. Ortoghonal ADC maps of three consecutive slices were acquired, with the diffusion encoding gradient oriented in the H-F (B o), L-R or A-P directions with six b values (100, 200, 300, 500, 800, 1200 mm -2 .s), respectively. ADC values were calculated pixel by pixel by fitting the expression I g =I o e -b.ADC (MATLAB 7.4.0 R2007a). T1 and T2 of the water resonance in the SWNT´s suspensions were determined using inversion-recovery and Carr-Pucell.Meiboom.Gill sequences at 1.5T in a Bruker Minispec platform.

Angewandte Chemie International Edition 02/2010; 49(10):1813-5. · 11.34 Impact Factor

  1. ZADERENKO, M. C. LOPEZ, P. BALLESTEROS

ABSTRACT: ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

ChemInform 01/2010; 28(5).

Christa Seipelt, Pilar Lopez, Thomas Kirschgen, Andreas Doelle,Manfred D. Zeidler, Isabel Fonseca, Felix H. Cano, Paloma Ballesteros

ChemInform 01/2010; 30(20).

  1. C. LOPEZ, N. JAGEROVIC, P. BALLESTEROS

ABSTRACT: The title new homochiral ligand has been prepared regioselectively by reaction of 2-hydroxymethyl-(4S,7R)-7,8,8-trimethyl-4,5,6,7-tetrahydro-4,7-methanoindazole with indazole in the presence of TosOH as catalyst using hexane or toluene as solvents. The structure has been unambiguously established by 1H and 13C NMR spectroscopy. Bis(indazol-1-yl)methane is obtained as secondary product as a consequence of an intermolecular dissociation-recombination process involved in the reaction.

ChemInform 01/2010; 26(15).

 

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Noninvasive multiparametric imaging of metastasis-permissive microenvironments in a human prostate cancer xenograft.

Marie-France Penet, Arvind P Pathak, Venu Raman, Paloma Ballesteros, Dmitri Artemov, Zaver M Bhujwalla

ABSTRACT: Metastasis continues to be one of the major causes of mortality from prostate cancer. Because human malignant cell lines metastasize more readily from orthotopic sites than from heterotopic sites, to identify metastasis-permissive tumor microenvironments, we used noninvasive imaging to compare the in vivo vascular, metabolic, and physiologic characteristics of a human prostate cancer xenograft implanted orthotopically in the prostate or s.c. in the flank. Hypoxia was detected in these xenografts by placing an enhanced green fluorescence protein optical reporter under the control of a hypoxia response element. A multiparametric analysis of hypoxia, extracellular pH, vascularization, and metabolism provided a characterization of environments that are permissive for metastasis to occur. We found that orthotopic tumors, which metastasized more easily, were characterized by higher vascular volume, permeability, and total choline and a more acidic extracellular pH. Interestingly, metastatic deposits in the lymph nodes as well as cancer cells in ascites fluid were found to be hypoxic, explaining, in part, the refractory nature of metastatic disease. These results also provide the basis for clinically translatable noninvasive imaging markers for predicting metastatic risk in prostate cancer.

Cancer Research 10/2009; 69(22):8822-9. · 9.28 Impact Factor

 

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The turnover of the H3 deuterons from (2-13C) glutamate and (2-13C) glutamine reveals subcellular trafficking in the brain of partially deuterated rats.

Sebastián Cerdán, Alejandra Sierra, Luis L Fonseca, Paloma Ballesteros, Tiago B Rodrigues

ABSTRACT: We investigated by 13C NMR the turnover of the H3 deuterons of (2-13C) glutamate and (2-13C) glutamine in the brain of partially deuterated rats. Adult animals (150-200 g) fed ad libitum received 50% 2H2O or tap water 9 days before infusing (1-13C) glucose or (2-13C) acetate for 5, 10, 15, 30, 60, or 90 min. The brains were then funnel-frozen and acid extracts were prepared and analyzed by high-resolution 13C NMR. The deuteration of one or the two H3 hydrogens of (2-13C) glutamate or glutamine resulted in single (-0.07 ppm) or double (-0.14 ppm) isotopic shifts upfield of the corresponding C2 perprotonated resonance, demonstrating two sequential deuteration steps. The faster monodeuteration generated 3R or 3S (2-13C, 3-2H) glutamate or glutamine through the alternate activities of cerebral aconitase or isocitrate dehydrogenase, respectively. The slower process produced bideuterated (2-13C, 3,3′-2H2) glutamate or glutamine through the consecutive activity of both enzymes. The kinetics of deuteration was fitted to a Michaelis-Menten model including the apparent K(m)’ and Vmax’ values for the observed deuterations. Our results revealed different kinetic constants for the alternate and consecutive deuterations, suggesting that these processes were caused by the different cytosolic or mitochondrial isoforms of aconitase and isocitrate dehydrogenase, respectively. The deuterations of (2-13C) glutamate or glutamine followed also different kinetics from (1-13C) glucose or (2-13C) acetate, revealing distinct deuteration environments in the neuronal or glial compartments.

Journal of Neurochemistry 05/2009; 109 Suppl 1:63-72. · 4.24 Impact Factor

Elena Perez-Mayoral, Jordi Soler-Padros, Viviana Negri, Sebastian Cerdan, Paloma Ballesteros

ChemInform 01/2009; 40(12).

Elena Pérez-Mayoral, Rosa M. Martín-Aranda, Antonio J. López-Peinado, Paloma Ballesteros, Arnošt Zukal, Jiří Čejka

ABSTRACT: Acetals/ketals derived from the aldehydes/ketones are easily prepared under solventless conditions. The process is heterogeneously catalysed using acid or basic mesoporous molecular sieves Al-SBA-15 and (Cs)Al-SBA-15. The catalytic procedure herein reported is applied to the preparation of the key intermediates for the synthesis of {3-[(2R,3R,4R,5R)-(2,3,4,5-tetrahydroxyhexane-1,6-diyl)]}di-1H-imidazole 2 with potential biomedical applications.

Topics in Catalysis 01/2009; 52(1):148-152. · 2.22 Impact Factor

  1. Ballesteros, E. Pérez-Mayoral, M. Benito, S. Cerdán

ABSTRACT: We review the different methods for measuring pH by magnetic resonance imaging and magnetic resonance spectroscopy and discuss their potential diagnostic repercussions. We begin with a brief description of intra- and extracellular pH regulation in physiological and pathological conditions. Then we present the main 31P or 1H magnetic resonance spectroscopy procedures, which are based on the dependence of the pH on the chemical displacements of the intrinsic intracellular inorganic phosphate or of the H2 proton of imidazole in extrinsic indicators. Finally, we describe the procedures that use magnetic resonance imaging, whose main tool is the dependence of the pH (i) on the relaxivity of certain paramagnetic contrast agents, or (ii) on the processes of magnetic transference between diamagnetic molecules (DIACEST) or paramagnetic molecules (PARACEST) and the free water in the tissues. We briefly illustrate the potential clinical applications of these new procedures.

Radiología. 12/2008; 50(6).

P Ballesteros, E Pérez-Mayoral, M Benito, S Cerdán

ABSTRACT: We review the different methods for measuring pH by magnetic resonance imaging and magnetic resonance spectroscopy and discuss their potential diagnostic repercussions. We begin with a brief description of intra- and extra-cellular pH regulation in physiological and pathological conditions. Then we present the main 31P or 1H magnetic resonance spectroscopy procedures, which are based on the dependence of the pH on the chemical displacements of the intrinsic intracellular inorganic phosphate or of the H2 proton of imidazole in extrinsic indicators. Finally, we describe the procedures that use magnetic resonance imaging, whose main tool is the dependence of the pH (i) on the relaxivity of certain paramagnetic contrast agents, or (ii) on the processes of magnetic transference between diamagnetic molecules (DIACEST) or paramagnetic molecules (PARACEST) and the free water in the tissues. We briefly illustrate the potential clinical applications of these new procedures.

Radiología 01/2008; 50(6):463-70; quiz 470.

Elena Pérez-Mayoral, Viviana Negri, Jordi Soler-Padrós, Sebastián Cerdán, Paloma Ballesteros

ABSTRACT: We provide a brief overview of the chemistry and most relevant properties of paramagnetic and diamagnetic contrast agents (CAs) for Magnetic Resonance Imaging and Magnetic Resonance Spectroscopic Imaging. Paramagnetic CAs for MRI consist mainly of Gd(III) complexes from linear or macrocyclic polyaminopolycarboxylates. These agents reduce, the relaxation times T1 and T2 of the water protons in a concentration dependent manner, increasing selectively MRI contrast in those regions in which they accumulate. In most instances they provide anatomical information on the localization of lesions and in some specific cases they may allow to estimate some physiological properties of tissues including mainly vascular performance. Because of its ability to discriminate easily between normal and diseased tissue, extracellular pH (pHe) has been added recently, to the battery of variables amenable to MRI investigation. A variety of Gd(III) containing macrocycles sensitive to pH, endogenous or exogenous polypeptides or even liposomes have been investigated for this purpose, using the pH dependence of their relaxivity or magnetization transfer rate constant (chemical exchange saturation transfer, CEST). Many environmental circumstances in addition to pH affect, however, relaxivity or magnetization transfer rate constants of these agents, making the results of pH measurements by MRI difficult to interpret. To overcome these limitations, our laboratory synthesized and developed a novel series of diamagnetic CAs for Magnetic Resonance Spectroscopic Imaging, a new family of monomeric and dimeric imidazolic derivatives able to provide unambiguous measurements of pHe, independent of water relaxivity, diffusion or exchange.

European Journal of Radiology 01/2008; · 2.16 Impact Factor

 

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Kinetic properties of the redox switch/redox coupling mechanism as determined in primary cultures of cortical neurons and astrocytes from rat brain.

Belén G Ramírez, Tiago B Rodrigues, Inês R Violante, Fátima Cruz, Luís L Fonseca, Paloma Ballesteros, M Margarida C A Castro, María L García-Martín, Sebastián Cerdán

ABSTRACT: We investigate the mechanisms underlying the redox switch/redox coupling hypothesis by characterizing the competitive consumption of glucose or lactate and the kinetics of pyruvate production in primary cultures of cortical neurons and astrocytes from rat brain. Glucose consumption was determined in neuronal cultures incubated in Krebs ringer bicarbonate buffer (KRB) containing 0.25-5 mM glucose, in the presence and absence of 5 mM lactate as an alternative substrate. Lactate consumption was measured in neuronal cultures incubated with 1-15 mM lactate, in the presence and absence of 1 mM glucose. In both cases, the alternative substrate increased the K(m) (mM) values for glucose consumption (from 2.2 +/- 0.2 to 3.6 +/- 0.1) or lactate consumption (from 7.8 +/- 0.1 to 8.5 +/- 0.1) without significant changes on the corresponding V(max). This is consistent with a competitive inhibition between the simultaneous consumption of glucose and lactate. When cultures of neurons or astrocytes were incubated with increasing lactate concentrations 1-20 mM, pyruvate production was observed with K(m) (mM) and V(max) (nmol/mg/h) values of 1.0 +/- 0.1 and 109 +/- 4 in neurons, or 0.28 +/- 0.1 and 342 +/- 54 in astrocytes. Thus, astrocytes or neurons are able to return to the incubation medium as pyruvate, a significant part of the lactate consumed. Present results support the reversible exchange of reducing equivalents between neurons and astrocytes in the form of lactate or pyruvate. Monocarboxylate exchange is envisioned to operate under near equilibrium, with the transcellular flux directed thermodynamically toward the more oxidized intracellular redox environment.

Journal of Neuroscience Research 12/2007; 85(15):3244-53. · 2.73 Impact Factor

PUBLICATIONS

Jordi Soler-Padrós, Elena Pérez-Mayoral, Laura Domínguez, Pilar López-Larrubia, Elena Soriano, José Luis Marco-Contelles,Sebastian Cerdan, Paloma Ballesteros

ABSTRACT: We describe the synthesis of 1,omega-di-1H-imidazoles 2 and 3, derived from l-threitol and d-mannitol, respectively, showing suitable magnetic and toxicological properties, as novel extracellular pH indicators for 1H spectroscopic imaging by magnetic resonance methods.

Journal of Medicinal Chemistry 10/2007; 50(18):4539-42. · 5.48 Impact Factor

 

 

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Serial in vivo spectroscopic nuclear magnetic resonance imaging of lactate and extracellular pH in rat gliomas shows redistribution of protons away from sites of glycolysis.

Peggy Provent, Marina Benito, Bassem Hiba, Régine Farion, Pilar López-Larrubia, Paloma Ballesteros, Chantal Rémy, Christoph Segebarth, Sebastián Cerdán, Jonathan A Coles, María Luisa García-Martín

ABSTRACT: The acidity of the tumor microenvironment aids tumor growth, and mechanisms causing it are targets for potential therapies. We have imaged extracellular pH (pHe) in C6 cell gliomas in rat brain using 1H magnetic resonance spectroscopy in vivo. We used a new probe molecule, ISUCA [(+/-)2-(imidazol-1-yl)succinic acid], and fast imaging techniques, with spiral acquisition in k-space. We obtained a map of metabolites [136 ms echo time (TE)] and then infused ISUCA in a femoral vein (25 mmol/kg body weight over 110 min) and obtained two consecutive images of pHe within the tumor (40 ms TE, each acquisition taking 25 min). pHe (where ISUCA was present) ranged from 6.5 to 7.5 in voxels of 0.75 microL and did not change detectably when [ISUCA] increased. Infusion of glucose (0.2 mmol/kg.min) decreased tumor pHe by, on average, 0.150 (SE, 0.007; P < 0.0001, 524 voxels in four rats) and increased the mean area of measurable lactate peaks by 54.4 +/- 3.4% (P < 0.0001, 287 voxels). However, voxel-by-voxel analysis showed that, both before and during glucose infusion, the distributions of lactate and extracellular acidity were very different. In tumor voxels where both could be measured, the glucose-induced increase in lactate showed no spatial correlation with the decrease in pHe. We suggest that, although glycolysis is the main source of protons, distributed sites of proton influx and efflux cause pHe to be acidic at sites remote from lactate production.

Cancer Research 08/2007; 67(16):7638-45. · 9.28 Impact Factor

  1. Pérez‐Mayoral, E. Soriano, J. Pacheco‐Torres, P. Ballesteros

ABSTRACT: In the title mol­ecule, C9H9N3O6, all bond lengths and angles are normal. The crystal packing shows inter­molecular C—H⋯O hydrogen bonds, with H⋯O distances of 2.299 (16) and 2.374 (15) Å, which link the mol­ecules into ribbons.

Acta Crystallographica Section E Structure Reports Online 04/2007; 63(4). · 0.35 Impact Factor

 

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Synthetic approaches to heterocyclic ligands for Gd-based MRI contrast agents.

Elena Pérez-Mayoral, Jordi Soler-Padrós, Viviana Negri, Sebastián Cerdán, Paloma Ballesteros

ABSTRACT: Magnetic Resonance Imaging (MRI) methods are currently used in the clinic for the non invasive detection and characterization of a wide variety of pathologies. Increases in the diagnostic efficiency of MRI have been helped by both the design of dedicated MR sequences revealing specific aspects of the pathology and by the development of more sensitive and selective Contrast Agents (CAs), capable of more precisely delineating the borderline regions. In the present review we focus on the synthetic strategies used to obtain MRI CAs containing heterocyclic rings.

Molecules 02/2007; 12(8):1771-95. · 2.10 Impact Factor

 

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Synthetic Approaches to Heterocyclic Ligands for Gd-Based MRI Contrast Agents

Pérez-Mayoral Elena, Soler-Padrós Jordi, Negri Viviana,Cerdán Sebastián, Ballesteros Paloma

ABSTRACT: Magnetic Resonance Imaging (MRI) methods are currently used in the clinic for the non invasive detection and characterization of a wide variety of pathologies. Increases in the diagnostic efficiency of MRI have been helped by both the design of dedicated MR sequences revealing specific aspects of the pathology and by the development of more sensitive and selective Contrast Agents (CAs), capable of more precisely delineating the borderline regions. In the present review we focus on the synthetic strategies used to obtain MRI CAs containing heterocyclic rings.

Molecules. 01/2007;

  1. Pérez-Mayoral, E. Soriano, J. Pacheco-Torres, P. Ballesteros

Acta Crystallographica Section E-structure Reports Online – ACTA CRYSTALLOGR E-STRUCT REP. 01/2007; 63(4).

Jesus Pacheco-Torres, Elena Perez-Mayoral, Elena Soriano, Pilar Lopez-Larrubia, Olivier Ouari, Araceli Gonzalez-Cortes, Sebastian Cerdan, Paloma Ballesteros

ABSTRACT: ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

ChemInform 01/2007; 38(13).

 

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Experimental and theoretical study of lanthanide complexes based on linear and macrocyclic polyaminopolycarboxylic acids containing pyrazolylethyl arms.

Elena Pérez-Mayoral, Elena Soriano, Sebastián Cerdán, Paloma Ballesteros

ABSTRACT: We report the synthesis of two novel Gd(III)-complexes derived from linear and macrocyclic polyaminopolycarboxylic acids 1 and 2, which contain a 3,5- dimethylpyrazolyl-ethyl arm, and a study of their relaxivity properties. The relationships between the experimental and theoretical results have provided interesting information about the kinetic and thermodynamic stability of these complexes.

Molecules 02/2006; 11(5):345-56. · 2.10 Impact Factor

 

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Experimental and Theoretical Study of Lanthanide Complexes Based on Linear and Macrocyclic Polyaminopolycarboxylic Acids Containing Pyrazolylethyl Arms

Pérez-Mayoral Elena, Soriano Elena, Cerdán Sebastián, Ballesteros Paloma

ABSTRACT: We report the synthesis of two novel Gd(III)-complexes derived from linear and macrocyclic polyaminopolycarboxylic acids 1 and 2, which contain a 3,5- dimethylpyrazolyl-ethyl arm, and a study of their relaxivity properties. The relationships between the experimental and theoretical results have provided interesting information about the kinetic and thermodynamic stability of these complexes.

Molecules. 01/2006;

Jose Alvarez-Pérez, Paloma Ballesteros, Sebastián Cerdán

ABSTRACT: We investigate microscopic pH heterogeneity within tumor spheroids using a novel 1H NMR methodology that provides high resolution measurements of intraspheroidal pH. High resolution microscopic images of intraspheroidal pH were obtained by 1H NMR using chemical shift selective excitation of the H2 resonance of imidazole added to the incubation medium. Imidazole accumulated in the intraspheroidal space in a pH dependent manner. Maps of intraspheroidal pH could be obtained by transforming pixel by pixel (32 x 32 micro) the regional variation of imidazole H2 intensity into a relative pH scale. Our analysis revealed drastic intraspheroidal pH alterations depending on the size of the spheroid, ca. 0.6 pH units more acidic in the necrotic core than in the periphery, for spheroids of 600 mum diameter. The presence of concentric regions having similar intraspheroidal pH was consistently observed. The thickness of these regions decreased from pH 7.2 to pH 6.8 and increased below the latter pH value. Our observations are compatible with the general model of spheroid growth where the more external layers of cells are in active growth and depict more alkaline pH values while the inner layers remain quiescent or evolve to a necrotic core, depicting more acidic pH values.

MAGMA Magnetic Resonance Materials in Physics Biology and Medicine 01/2006; 18(6):293-301. · 1.35 Impact Factor

Ballesteros Paloma, Pérez-Mayoral Elena, García-Amo María,López-Larrubia Pilar, Cerdán Sebastián

Heterocycles 11/2005; 65(7). · 0.91 Impact Factor

Elena Soriano, Paloma Ballesteros, José Marco-Contelles

ABSTRACT: The PtCl2-mediated cycloisomerization of hept-1-en-6-ynes functionalized at propargylic positions shows a high versatility and may afford different kinds of products. On the basis of a broad DFT computational study, mechanistic understandings of these processes are provided. The results suggest that these reactions could proceed through cyclopropyl platinum carbenes formed by endo or by exo cyclization routes. The role of the propargylic substituent and the additional alkene chain for dienyne precursors in the course of each type of cycloisomerization is discussed. Thus, although the metathesis process and formation of polycyclic adducts involves an initial 5-exo cyclopropanation path, a propargylic acyl group promotes the formation of bicyclic enol esters by an initial endo cyclopropanation, followed by [1,2]-acyl migration. This bulky propargylic group also inhibits other cycloisomerization reactions due to steric interactions, such as the Alder-ene process, and simultaneously allows an easy [1,2]-acyl migration by anchimeric assistance to yield bicyclic [n.1.0] enol esters.

Organometallics. 05/2005; 24(13).

Elena Soriano, Paloma Ballesteros, José Marco-Contelles

ABSTRACT: The PtCl2-mediated intramolecular cycloisomerization of 1,6-enynes functionalized at propargylic positions shows a high versatility and can give rise to a variety of products with potential synthetic applications. A broad computational study at the DFT level is reported to provide a better mechanistic understanding of these reactions and of the factors that control the course of these processes. For every type of cycloisomerization, several reasonable pathways have been proposed and evaluated. The results suggest that these reactions probably share common steps and could proceed through the formation of cyclopropyl platinum carbenes by endo- or by exo-cyclization routes. The role of the propargylic substituent and the additional alkene chain for dienyne precursors is also discussed. The metathesis process involves an initial 5-exo cyclopropanation path, in common with the formation of polycyclic adducts, but it is retarded or inhibited by the presence of an additional alkene chain.

Organometallics 05/2005; 24(13). · 4.25 Impact Factor

 

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Futile cycling of lactate through the plasma membrane of C6 glioma cells as detected by (13C, 2H) NMR.

Tiago B Rodrigues, Heather L Gray, Marina Benito, Susana Garrido, Alejandra Sierra, Carlos F Geraldes, Paloma Ballesteros,Sebastián Cerdán

ABSTRACT: We report a novel ((13)C, (2)H) nuclear magnetic resonance (NMR) procedure to investigate lactate recycling through the monocarboxylate transporter of the plasma membrane of cells in culture. C6 glioma cells were incubated with [3-(13)C]lactate in Krebs-Henseleit Buffer containing 50% (2)H(2)O (vol/vol) for up to 30 hr. (13)C NMR analysis of aliquots progressively taken from the medium, showed: (1) a linearly decreasing singlet at approximately 20.85 parts per million (ppm; -0.119 micromol/mg protein/hr) derived from the methyl carbon of [3-(13)C]lactate; and (2) an exponentially increasing shifted singlet at approximately 20.74 ppm (0.227 micromol/ mg protein/hr) from the methyl carbon of [3-(13)C, 2-(2)H]lactate. The shifted singlet appears because during its transit through the cytosol, [3-(13)C]lactate generates [3-(13)C, 2-(2)H]lactate in the lactate dehydrogenase (LDH) equilibrium, which may return to the incubation medium through the reversible monocarboxylate carrier. The methyl group of [3-(13)C, 2-(2)H]lactate is shifted -0.11 ppm with respect to that of [3-(13)C]lactate, making it possible to distinguish between both molecules by (13)C NMR. During incubations with 2.5 mM [1-(13)C]glucose and 3.98 mM [U-(13)C(3)]lactate or with 2.5 mM [1-(13)C]glucose and 3.93 mM [2-(13)C]pyruvate, C2-deuterated lactate was produced only from [1-(13)C]glucose or [U-(13)C(3)]lactate, revealing that this deuteration process is redox sensitive. When [1-(13)C]glucose and [U-(13)C(3)]lactate were used as substrates, no significant [3-(13)C]lactate production from [1-(13)C]glucose was detected, suggesting that glycolytic lactate production may be stopped under the high lactate concentrations prevailing under mild hypoxic or ischemic episodes or during cerebral activation.

Journal of Neuroscience Research 01/2005; 79(1-2):119-27. · 2.73 Impact Factor

Elena Soriano, Paloma Ballesteros, José Marco-Contelles

ABSTRACT: A mechanistic study based on DFT theoretical calculations for the PtCl(2)-catalyzed formation of bicyclic adducts from heteroatom tethered 1,6-enynes is reported. Different reaction pathways have been taken into account and the results are discussed. This analysis clearly reveals that the kinetically preferred pathway involves an initial 6-endo-cyclization from a triggered reactant complex by pi-complexation of Pt(II) onto the alkyne to form a cyclopropyl platina-carbene intermediate, followed by a [1,2]-hydrogen shift.

The Journal of Organic Chemistry 12/2004; 69(23):8018-23. · 4.64 Impact Factor

 

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Cerebral glucose metabolism and the glutamine cycle as detected by in vivo and in vitro 13C NMR spectroscopy.

María A García-Espinosa, Tiago B Rodrigues, Alejandra Sierra,Marina Benito, Carla Fonseca, Heather L Gray, Brenda L Bartnik,María L García-Martín, Paloma Ballesteros, Sebastián Cerdán

ABSTRACT: We review briefly 13C NMR studies of cerebral glucose metabolism with an emphasis on the roles of glial energetics and the glutamine cycle. Mathematical modeling analysis of in vivo 13C turnover experiments from the C4 carbons of glutamate and glutamine are consistent with: (i) the glutamine cycle being the major cerebral metabolic route supporting glutamatergic neurotransmission, (ii) glial glutamine synthesis being stoichiometrically coupled to glycolytic ATP production, (iii) glutamine serving as the main precursor of neurotransmitter glutamate and (iv) glutamatergic neurotransmission being supported by lactate oxidation in the neurons in a process accounting for 60-80% of the energy derived from glucose catabolism. However, more recent experimental approaches using inhibitors of the glial tricarboxylic acid (TCA) cycle (trifluoroacetic acid, TFA) or of glutamine synthase (methionine sulfoximine, MSO) reveal that a considerable portion of the energy required to support glutamine synthesis is derived from the oxidative metabolism of glucose in the astroglia and that a significant amount of the neurotransmitter glutamate is produced from neuronal glucose or lactate rather than from glial glutamine. Moreover, a redox switch has been proposed that allows the neurons to use either glucose or lactate as substrates for oxidation, depending on the relative availability of these fuels under resting or activation conditions, respectively. Together, these results suggest that the coupling mechanisms between neuronal and glial metabolism are more complex than initially envisioned.

Neurochemistry International 01/2004; 45(2-3):297-303. · 2.65 Impact Factor

Elena Soriano, Sebastián Cerdán, Paloma Ballesteros

ABSTRACT: We have estimated the pKa values of different series of imidazol-1-ylalcanoic acid derivatives using combinations of semiempirical or ab initio methods and two semiempirical solvation models SM2 and SM5.4. None of these procedures was able to describe the zwitterionic structure of the carboxylic monoacids series as their most stable form determined experimentally in solution. Under these conditions, a comparison of the theoretical and experimental pKa values showed RMS differences ranging from 1.43 to 3.04 pKa units. As an alternative strategy we describe here a mathematical model for pKa determination based on quantitative structure–property relationships. The model uses two quantum chemical descriptors, the natural atomic charge on the N3 proton (qH+) and the frontier orbital energy (εL), allowing the determination of pKa values for every compound of a given series with a reasonable computational effort. A linear relationship is described among pKa, qH+, εL and the number of ester groups in the molecule n. Multiple linear regression analysis of the available series of imidazol-1-ylalcanoic compounds allowed to obtain the expression which reproduced the experimental values within 0.1 pKa units.

Journal of Molecular Structure: THEOCHEM. 01/2004;

 

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A novel series of complexones with bis- or biazole structure as mixed ligands of paramagnetic contrast agents for MRI.

Elena P Mayoral, María García-Amo, Pilar López, Elena Soriano,Sebastián Cerdán, Paloma Ballesteros

ABSTRACT: We describe the syntheses, physicochemical properties and biological evaluation of a novel series of complexones containing bis- or biazoles moieties and two iminodiacetic acid units as novel ligands for paramagnetic lanthanides. The complexones were prepared by reaction of the corresponding 1,1′-bishaloethylbi- or bispyrazoles with methyl iminodiacetate and subsequent NaOH hydrolysis. 1,1′-Bisbromoethyl precursors were obtained by direct alkylation with an excess of 1,2-dibromoethane, or by heating the corresponding alcohol in HCl. Sigmoidal binding isotherms and MO calculations supported as most stable structures in solution, those containing two Gd(III) atoms bound per molecule of complexone with half saturation values S(0.5) (M(-1), 22 degrees C, pH 7.2) in the range 6.5 10(-6)<S(0.5)<36.1 10(-6). Relaxivity properties [r(1), r(2), s(-1) mM(-1) Gd(III)] determined at 1.5 Tesla gave values (12.0<r(1)<17.7, 12.2<r(2)<20), improving significantly the relaxivities of reference compounds such as Gd(III)EDTA (5.2, 5.6) or Gd(III)DTPA (4.30, 4.30). These improvements involve mainly increased hydration and slower rotational motions. In vitro toxicity experiments are reported.

Bioorganic & Medicinal Chemistry 12/2003; 11(24):5555-67. · 2.95 Impact Factor

José Marco-Contelles, Laura Domı́nguez, Shazia Anjum, Paloma Ballesteros, Elena Soriano, Denis Postel

ABSTRACT: The triphenyltin hydride-mediated free radical cyclization of the radical precursors 1, 7 and 12 is described. This is a new stereoselective entry into the 1,7 dioxaspiro[4,4]nonane ring system.

Tetrahedron Asymmetry 01/2003; 14(19):2865-2869. · 2.17 Impact Factor

Mayoral Elena Perez, Ballesteros Paloma

ChemInform 01/2003; 34(20).

  1. Cerdan, T. B. Rodrigues, P. Ballesteros, P. Lopez, E. P. Mayoral

Magnetic Resonance in Food Science: Latest Developments, Edited by P. S. Belton, A. M. Gil, G. A. Webb, D. Rutledge, 01/2003: pages 121-135; The Royal Society of Chemistry., ISBN: 9780854048861

 

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Combined vascular and extracellular pH imaging of solid tumors.

Z M Bhujwalla, D Artemov, P Ballesteros, S Cerdan, R J Gillies, M Solaiyappan

ABSTRACT: The unique physiological environment of solid tumors, frequently characterized by areas of poor flow, hypoxia, high lactate and low extracellular pH (pHe), influences vascularization, invasion and metastasis. Thus, vascularization and the physiological and metabolic environment play permissive (and conversely preventive) roles in invasion and metastasis. By using a multi-parametric approach of combined vascular and spectroscopic imaging, we can begin to evaluate which combinations of vascular, metabolic and physiological regions in a solid tumor represent the highest ‘metastatic threat’. Here, we present measurements of pHe, vascular volume and permeability from co-localized regions within a solid tumor. These studies were performed for a group of metastatic (MDA-MB-231) and non-metastatic (MCF-7) human breast cancer xenografts. In this study, we have demonstrated the feasibility of such an approach, and presented methods of analyses to detect differences in patterns of combined parameters obtained from spatially co-registered regions in a solid tumor.

NMR in Biomedicine 05/2002; 15(2):114-9. · 3.56 Impact Factor

Paloma Ballesteros, Rosa M. Claramunt, Consuelo Escolastico, M. Dolores Santa Maria, Jose Elguero

The Journal of Organic Chemistry 04/2002; 57(6). · 4.64 Impact Factor

Maria Carmen Lopez, Rosa Maria Claramunt, Paloma Ballesteros

Journal of Organic Chemistry – J ORG CHEM. 04/2002; 57(19).

Paula Zaderenko, M. Soledad Gil, Paloma Ballesteros, Sebastian Cerdan

Journal of Organic Chemistry – J ORG CHEM. 04/2002; 59(21).

Halvor N. Christensen, Mary E. Handlogten, Jaydutt V. Vadgama,Elena De la Cuesta, Paloma Ballesteros, Gregorio G. Trigo,Carmen Avendano

Journal of Medicinal Chemistry – J MED CHEM. 04/2002; 26(10).

María L García-Martín, María A García-Espinosa, Paloma Ballesteros, Marta Bruix, Sebastián Cerdán

ABSTRACT: (13)C NMR monitored the dynamics of exchange from specific hydrogens of hepatic [2-(13)C]glutamate and [3-(13)C]aspartate with deuterons from intracellular heavy water providing information on alpha-ketoglutarate/glutamate exchange and subcellular compartmentation. Mouse livers were perfused with [3-(13)C]alanine in buffer containing or not 50% (2)H(2)O for increasing periods of time (1 min < t < 30 min). Liver extracts prepared at the end of the perfusions were analyzed by high resolution (13)C NMR (150.13 MHz) with (1)H decoupling only and with simultaneous (1)H and (2)H decoupling. (13)C-(2)H couplings and (2)H-induced isotopic shifts observed in the glutamate C2 resonance, allowed to estimate the apparent rate constants (forward, reverse; min(-1)) for (i) the reversible exchange of [2-(13)C]glutamate H2 as catalyzed mainly by aspartate aminotransferase (0.32, 0.56), (ii) the reversible exchange of [2-(13)C]glutamate H3(proS) as catalyzed by NAD(P) isocitrate dehydrogenase (0.1, 0.05), and (iii) the irreversible exchanges of glutamate H3(proR) and H3(proS) as catalyzed by the sequential activities of mitochondrial aconitase and NAD isocitrate dehydrogenase of the tricarboxylic acid cycle (0.035), respectively. A similar approach allowed to determine the rates of (1)H-(2)H exchange for the H2 (0.4, 0.5) or H3(proR) (0.3, 0.2) or the H2 and H3(proS) hydrogens (0.20, 0.23) of [3-(13)C]aspartate isotopomers. The ubiquitous subcellular localization of (1)H-(2)H exchange enzymes and the exclusive mitochondrial localization of pyruvate carboxylase and the tricarboxylic acid cycle resulted in distinctive kinetics of deuteration in the H2 and either or both H3 hydrogens of [2-(13)C]glutamate and [3-(13)C]aspartate, allowing to follow glutamate and aspartate trafficking through cytosol and mitochondria.

Journal of Biological Chemistry 04/2002; 277(10):7799-807. · 4.60 Impact Factor

F Cruz, M Villalba, M A García-Espinosa, P Ballesteros, E Bogónez, J Satrústegui, S Cerdán

ABSTRACT: The intracellular compartmentation of pyruvate in primary cultures of cortical neurons was investigated by high resolution (13)C NMR using mixtures of different pyruvate precursors conveniently labeled with (13)C or unlabeled. Cells were incubated with 1-5 mM (1-(13)C, 1,2-(13)C(2) or U-(13)C(6)) glucose only or with mixtures containing 1.5 mM (1-(13)C or U-(13)C(6)) glucose, 0.25-2.5 mM (2-(13)C or 3-(13)C) pyruvate and 1 mM malate. Extracts from cells and incubation media were analyzed by (13)C NMR to determine the relative contributions of the different precursors to the intracellular pyruvate pool. When ((13)C) glucose was used as the sole substrate fractional (13)C enrichments and (13)C isotopomer populations in lactate and glutamate carbons were compatible with a unique intracellular pool of pyruvate. When mixtures of ((13)C) glucose, ((13)C) pyruvate and malate were used, however, the fractional (13)C enrichments of the C2 and C3 carbons of lactate were higher than those of the C2 and C3 carbons of alanine and depicted a different (13)C isotopomer distribution. Moreover, neurons incubated with 1 mM (1,2-(13)C(2)) glucose and 0.25-5 mM (3-(13)C) pyruvate produced exclusively (3-(13)C) lactate, revealing that extracellular pyruvate is the unique precursor of lactate under these conditions. These results reveal the presence of two different pools of intracellular pyruvate; one derived from extracellular pyruvate, used mainly for lactate and alanine production and one derived from glucose used primarily for oxidation. A red-ox switch using the cytosolic NAD(+)/NADH ratio is proposed to modulate glycolytic flux, controlling which one of the two pyruvate pools is metabolized in the tricarboxylic acid cycle when substrates more oxidized or reduced than glucose are used.

Journal of Neuroscience Research 01/2002; 66(5):771-81. · 2.73 Impact Factor

Gwenael Herigault, Chantal Remy, Regine Farion, Paloma Ballesteros, Jonathan A. Coles, Sebastian Cerdan, Anne Ziegler

ABSTRACT: The value of extracellular pH (pHe) in tumors is an important factor in prognosis and choice of therapy. We demonstrate here that pHe can be mapped in vivo in a rat brain glioma by 1H magnetic resonance spectroscopic imaging (SI) of the pH buffer ()2-imidazole-1-yl-3-ethoxycarbonylpropionic acid (IEPA). 1H SI also allowed us to map metabolites, and, to better under- stand the determinants of pHe, we compared maps of pHe, metabolites, and the distribution of the contrast agent gadolinium1,4,7,10-tetraazacyclodode- cane-N,N,N,N-tetraaceticacid (Gd-DOTA). C6 cells injected in caudate nuclei of four Wistar rats gave rise to gliomas of 10 mm in diameter. Three mmols of IEPA were injected in the right jugular vein from t 0t ot 60 min. From t 50 min to t 90 min, spin-echo 1H SI was performed with an echo time of 40 ms in a 2.5-mm slice including the glioma (nominal voxel size, 2.2 l). IEPA resonances were detected only within the glioma and were intense enough for pHe to be calculated from the chemical shift of the H2 resonance in almost all voxels of the glioma. 1H spectroscopic images with an echo time of 136 ms were then acquired to map metabolites: lactate, choline- containing compounds (tCho), phosphocreatine/creatine, and N-acetylaspar- tate. Finally, T1-weighted imaging after injection of a bolus of Gd-DOTA gave a map indicative of extravasation. On average, the gradient of pHe (measured where sufficient IEPA was present) from the center to the periphery was not statistically significant. Mean pHe was calculated for each of the four gliomas, and the average was 7.084 0.017 ( SE; n 4 rats), which is acid with respect to pHe of normal tissue. After normalization of spectra to their water peak, voxel-by-voxel comparisons of peak areas showed that N-acetylaspar- tate, a marker of neurons, correlated negatively with IEPA (P < 0.0001) and lactate (P < 0.05), as expected of a glioma surrounded by normal tissue. tCho (which may indicate proliferation) correlated positively with pHe (P < 0.0001). Lactate correlated positively with tCho (P < 0.0001), phospho- creatine/creatine (P < 0.001), and Gd-DOTA (P < 0.0001). Although lactate is exported from cells in association with protons, within the gliomas, no evidence was observed that pHe was significantly lower where lactate con- centration was higher. These results suggest that lactate is produced mainly in viable, well-perfused, tumoral tissue from which proton equivalents are rapidly cleared.

Cancer Research 09/2001; 61(17). · 9.28 Impact Factor

Marı́a L. Garcı́a-Martı́n, Paloma Ballesteros, Sebastián Cerdán

Progress in Nuclear Magnetic Resonance Spectroscopy 01/2001; 39(1):41-77. · 8.71 Impact Factor

Paloma Ballesteros García

ABSTRACT: En: A distancia Madrid 2001, v. 19, n. 1 ; p. 23-32 Se ofrece un análisis sobre la aplicación de la imagen molecular para la mejora en la determinación de los diagnósticos médicos. Se explica la utilidad de la resonancia magnética dentro de los métodos de diagnósticos no invasivos, p. 32

http://www.redined.mec.es/oai/indexg.php?registro=008200230184. 01/2001;

 

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In vivo imaging of extracellular pH using 1H MRSI.

Robert van Sluis, Zaver M. Bhujwalla, Natarajan Raghunand, Paloma Ballesteros, José Alvarez, Sebastián Cerdán, Jean‐Philippe Galons, Robert J. Gillies

ABSTRACT: Tumor pH is physiologically important since it influences a number of processes relevant to tumorigenesis and therapy. Hence, knowledge of localized pH within tumors would contribute to understanding these processes. The destructiveness, poor spatial resolution, and poor signal-to-noise ratio (SNR) of current technologies (e.g., microelectrodes, 31P magnetic resonance spectroscopy) have limited such studies. An extrinsic chemical extracellular pH (pHe) probe is described that is used in combination with 1H magnetic resonance spectroscopic imaging to yield pHe maps with a spatial resolution of 1 x 1 x 4 mm3. The principle of the technique is demonstrated on a phantom. Further data are shown to demonstrate its application in vivo, and results agree with previously reported pH values. The accuracy of the reported pH measurements is <0.1 pH units, as derived from a detailed analysis of the errors associated with the technique, the description of which is included.

Magnetic Resonance in Medicine 04/1999; 41(4):743-50. · 3.40 Impact Factor

P López, C G Seipelt, P Merkling, L Sturz, J Alvarez, A Dölle, M D Zeidler, S Cerdán, P Ballesteros

ABSTRACT: The synthesis, physicochemical properties, and toxicological implications of a novel series of N-2-(azol-1(2)-yl)ethyliminodiacetic acids, useful as contrast agents for magnetic resonance imaging are reported. Compounds were prepared by alkylation of methyl iminodiacetate with N-2-bromoethylazoles and subsequent hydrolysis. Stability constants of the corresponding Gd(III) complexes and T1 and T2 relaxivities were determined and interpreted in terms of optimized geometries obtained by semiempirical PM3 calculations. Compounds show increased T2 relaxivity and decreased toxicity in vitro as compared to EDTA-Gd(III) complexes.

Bioorganic & Medicinal Chemistry 04/1999; 7(3):517-27. · 2.95 Impact Factor

A I García-Pérez, E A López-Beltrán, P Klüner, J Luque, P Ballesteros, S Cerdán

ABSTRACT: The role of molecular crowding and viscosity on the apparent translational diffusion coefficient (ADC) of small metabolites was investigated in different subcellular organelles using the pulse-field gradient spin-echo 1H NMR technique. ADCs of metabolites with increasing radius of gyration (0.7 A < RG < 4.5 A) were measured in the cytoplasm of rat or chicken erythrocytes, in the nucleus of chicken erythrocytes, and in isolated rat liver mitochondria. Metabolite ADCs in these systems were compared with the corresponding ADCs determined in model solutions of increasing bulk viscosity but different molecular crowding. For solutions having the same viscosity, metabolite ADCs decreased with increasing concentration of cosolutes. This effect is adequately described by the modified Stokes-Einstein relationship, ADC = k/RG (1 + 2.5Phi), where k is a constant for a given temperature and Phi is an obstruction factor reporting the fractional volume of solution occupied by cosolutes, a measure of the molecular crowding in the solution. Cytoplasmic values of Phi for metabolites of different sizes did not depend exclusively on metabolite RG but on additional factors including the chemical nature of the metabolite, the presence of diffusional barriers, and metabolite-specific binding sites. In the case of water, nuclear Phi values approached those of the extracellular space while mitochondrial Phi values were significantly higher than those of the cytoplasm. Taken together, these results reveal important differences in molecular crowding within the different subcellular compartments, suggesting considerable diffusional heterogeneity for small metabolites within the different intracellular organelles.

Archives of Biochemistry and Biophysics 02/1999; 362(2):329-38. · 3.04 Impact Factor

  1. Seipelt, P. Lopez, T. Kirschgen, A. Dölle, M. D. Zeidler, I. Fonseca, F. H. Cano, P. Ballesteros

ABSTRACT: Palladium(II)-promoted vicinal diamination of N-alkenylbenzimidazoles has been investigated. Dichlorobis(1-(alkenyl)benzimidazole)palladium(II) complexes were identified as initial reaction products which proved to be rather inert to the subsequent oxidative diamination required in the process. Instead, they were readily reduced by KBH4 to give the corresponding 1-alkylbenzazoles as the main reaction products. The crystal structure of the isolated complex trans-dichlorobis(1-(3-butenyl)benzimidazole)palladium(II) was determined by X-ray diffraction analysis.

Tetrahedron Letters 01/1999; 40:1739-1742. · 2.39 Impact Factor

Francisco Morales, Paloma Ballesteros

ABSTRACT: Automatic Proton Nuclear Magnetic Resonance (1H NMR) spectral based diagnosis malignant brain tumors is analyzed, using Neural Networks for classifying purposes. The Pattern Recognition has been split into its principal parts or subproblems, adapting each one of them to the special task of analyzing 1H NMR spectra. We study the principal algorithms needed for solving those problems, and finally a distributed object oriented classifying system is proposed, which attempts to solve the principal problems mentioned in each section.

Engineering Applications of Bio-Inspired Artificial Neural Networks, International Work-Conference on Artificial and Natural Neural Networks, IWANN ’99, Alicante, Spain, June 2-4, 1999, Proceedings, Volume II; 01/1999

  1. Zaderenko, M. S. Gil, P. López, P. Ballesteros, I. Fonseca, A. Albert

Acta crystallographica. Section B, Structural science 12/1997; 53(6):961-967. · 2.10 Impact Factor

Paula Zaderenko, M. Carmen López, Paloma Ballesteros

ABSTRACT: The regioselectivity of nucleophilic addition of azoles to unsymmetrical fumarates yielding the corresponding (+/-)-2-azol-1-ylsuccinates has been studied. The major regioisomer has been identified as the one obtained from the attack of the azole to the more congestive side of the double bond. These results have been interpreted in terms of HOMO-LUMO interactions using semiempirical AM1 molecular orbital calculations. Addition of amines as alternative heteronucleophiles has been also explored to confirm the regioselectivity. Neutral hydrolysis of the two n-butyl ethyl (+/-)-2-imidazol-1-ylsuccinate regioisomers 8a and 8b has shown that this hydrolysis takes place faster than with the corresponding symmetrical di-n-butyl (+/-)-2-imidazol-1-ylsuccinate, and the apparent rate of hydrolysis is independent of the size of the alcohol moiety.

The Journal of Organic Chemistry 11/1996; 61(20):6825-6828. · 4.64 Impact Factor

Pilar López, Paula Zaderenko, Jose Luis Balcazar, Isabel Fonseca,Félix Hernández Cano, Paloma Ballesteros

ABSTRACT: The crystal zwitterion structures of imidazol-1-ylacetic acid 1 and (±)-3-ethoxycarbonyl-2-imidazol-1-ylpropionic acid2 have been determined by X-ray diffraction analysis. Spectroscopic 13C NMR studies in the solid state, by the CP/MAS technique, and in solution have revealed the presence of the zwitterion structure in H2O and D2O solutions. Results have been complemented with 17O NMR and IR data.

Journal of Molecular Structure 03/1996; 377(2):105-112. · 1.60 Impact Factor

Molecular Dynamics of Hydantoins and Barbiturates Assessed by 1H, 13C, and 15N Relaxation Data

P Gruhlke, CG Seipelt, A Dölle, MD Zeidler, P Zaderenko, P Ballesteros, S Cerdan

ABSTRACT: The molecular dynamics of hydantoin,5,5-dimethylhydantoin,5,5-diphenylhydantoin, barbituric acid and 5-ethyl-5-phenylbarbituric acid in solution are determined to investigate the molecular basis for the activity of these neuroactive drugs. From dipolar 13C and 15N spin-lattice relaxation times the correlation times for the rotational dynamics of specific bond vectors are evaluated. Conclusions can be drawn concerning the anisotropy of the overall molecular rotational motion and the internal rotations of molecular segments. The translational molecular diffusion coefficients are obtained from self diffusion measurements by the pulsed gradients method. The observed differences in the dynamics as well as structural differences may account for the variation in the neuroactivity of the studied compounds.

Journal of the Chemical Society Perkin Transactions 2 01/1995;

ChemInform Abstract: Synthesis of New Bis(indazol-1-yl)phenylmethanes.
  1. LOPEZ,R. CLARAMUNT, P. BALLESTEROS

ABSTRACT: ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

ChemInform 07/1994; 25(28).

Imidazol-1-ylalkanoic acids as extrinsic 1H NMR probes for the determination of intracellular pH, extracellular pH and cell volume.

S Gil, P Zaderenzo, F Cruz, S Cerdán, P Ballesteros

ABSTRACT: The synthesis and biological evaluation of a novel series of extrinsic probes for intracellular pH (pHi), extracellular pH (pHo) and cell volume determination by 1H NMR is described. Imidazol-1-ylacetate, malonate, 3-glutarate and 2-succinate esters were synthesized by reaction of imidazole with alpha-bromo esters or with alpha, beta-unsaturated esters. The corresponding acids were prepared by hydrolysis. Rat erythrocytes were readily permeable to methyl imidazol-1-ylacetate, moderately permeable to diethyl 2-imidazol-1-ylsuccinate and impermeable to diethyl 3-imidazol-1-yl-glutarate esters. Imidazol-1-ylacetic acid was the only acid derivative which penetrated the erythrocyte interior when added directly to the incubation medium. Transport of the permeable compounds to the erythrocyte interior was non-saturable up to 200 mM added compound. Addition of methyl imidazol-1-ylacetate or diethyl 2-imidazol-1-ylsuccinate esters to erythrocyte suspensions, resulted in hydrolysis to imidazol-1-ylacetic acid and 2-imidazol-1-ylsuccinic acid mono-ethyl ester in the intracellular and extracellular spaces, respectively. pHi and pHo were determined from the different chemical shifts of the H-2 proton of the acid derivatives in the intracellular (H-2i) and extracellular (H-2o) compartments. In addition, the relative intracellular and extracellular volumes could be calculated from the areas of the intracellular and extracellular H-2 resonances.

Bioorganic & Medicinal Chemistry 06/1994; 2(5):305-14. · 2.95 Impact Factor

(2,5-Norbornadiene)rhodium(I) complexes with bis- and tris(azol-1-yl)methanes

Paloma Ballesteros, Concepcion Lopez, Carmen Lopez, Rosa M. Claramunt, Jose A. Jimenez, Mercedes Cano, Jose V. Heras,Elena Pinilla, Angeles Monge

Organometallics 04/1994; 13(1):289-297. · 4.25 Impact Factor

Synthesis of New Bis(indazol-1-yl)phenylmethanes

Ballesteros Paloma, Rosa M Claramunt, Paloma Ballesteros

Heterocycles 01/1994; 37(2). · 0.91 Impact Factor

The crystal and molecular structure of bis(indazol-1-yl)pyridin-2′-ylmethane (BIPM) and [Rh(BIPM)(NBD)]PF6

M.C.López Gallego-Preciado, P. Ballesteros, R.M. Claramunt, M. Cano, J.V. Heras, E. Pinilla, A. Monge

ABSTRACT: The syntheses of a new tripodal ligand bis(indazol-1-yl)pyridin-2′-ylmethane (BIPM) and of a cationic complex (Rh(BIPM)(NBD)]PF6, (NBD = 2,5-norbornadiene) are reported. Both compounds were characterized by infrared, 1H, and 13C NMR spectroscopy and by single crystal X-ray analysis. BIPM crystallizes in the monoclinic system in space group P21/n with an αβα helical conformation. The [Rh(BIPM)(NBD)]PF6 complex crystallizes in the monoclinic space group C/2c, the rhodium atom being pentacoordinate with a distorted trigonal bipyramidal geometry.

Journal of Organometallic Chemistry 05/1993; 450(s 1–2):237–244. · 2.30 Impact Factor

Synthesis of Bis(indazolyl)alkanes from 1-Hydroxyalkylindazoles
  1. C. Lopez,R. M. Claramunt, P. Ballesteros

ABSTRACT: ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

ChemInform 01/1993; 24(2):183-183.

Imidazol-1-ylalkanoate esters and their corresponding acids. A novel series of extrinsic 1H NMR probes for intracellular pH

M.S. Gil, F. Cruz, S. Cerdán, P. Ballesteros

ABSTRACT: A novel series of extrinsic probes for intracellular pH (pHi) determination by 1H NMR is described. Imidazol-1-ylacetate, malonate, 3-glutarate and 2-succinate esters were synthesized by reaction of imidazole either with α-bromoesters or with α,β-unsaturated esters. The corresponding acids were prepared by hydrolysis.

Bioorganic & Medicinal Chemistry Letters 12/1992; 2(12):1717–1722. · 2.33 Impact Factor

Studies on the Thermal Rearrangement of 2-Methoxypyridine N-Oxides to 1-Methoxypyridin-2-Ones

Paloma Ballesteros, Salvador Senent, José Elguero

ABSTRACT: A study of the influence of the solvent polarity on the rearrangement of 2-methoxypyridine N-oxides to 1-methoxypyridin–2-ones suggests an ionic mechanism.

Bulletin des Sociétés Chimiques Belges. 01/1990; 99(8).

A 1H and 13C nuclear magnetic resonance and X-ray diffraction study of the tautomerism of 2-hydroxy- and 2,3-dihydroxy-pyridine N-oxides. X-Ray molecular structure of 2-hydroxypyridine N-oxide

Paloma Ballesteros, Rosa Ma. Claramunt, Concepcion Foces-Foces, Alain Fruchier

ABSTRACT: From a 1H and 13C NMR study, in dimethyl sulphoxide, of twelve 2-hydroxy-, 2,3-dihydroxy-pyridines, 2,3-dihydroxypyridine N-oxides, and their methoxy derivatives it is possible to conclude that both pyridin-2-ones and 1-hydroxypyridine-2-ones exist in solution as 2-oxo tautomers. The molecular structure of 2-hydroxypyridine N-oxide has been determined by X-ray diffraction methods; as in solution, this compound exists in the crystal state as the 1-hydroxypyridin-2-one tautomer.

Journal of the Chemical Society Perkin Transactions 2 01/1990;

Synthesis and antifungal properties of some N,N’-bis-azolylarylmethanes.

P Ballesteros, R M Claramunt, M C López, J Elguero, G Gómez-Alarcón

CHEMICAL & PHARMACEUTICAL BULLETIN 07/1988; 36(6):2036-41. · 1.38 Impact Factor

Enantiomeric Resolution of 3,5’Dimethyl4,4′-dibromo-1,1′-bispyrazolylphenylmethane by Liquid Chromatography on Triacetylcellilose

Ballesteros Paloma, Paloma Ballesteros, Rosa M. Claramunt, M. del Carmen L. Gallego-Preciado, Chiritian Roussel, Ahmed Chemlal

Heterocycles 01/1988; 27(2). · 0.91 Impact Factor

Study of the catalytic properties of tris (3,6-dioxaheptyl) amine (tda-1) in heteroaromatic nucleophilic substitution of chloropyridines and their n-oxides
  1. Ballesteros,R.M. Claramunt,J. Elguero

ABSTRACT: Catalytic properties of tris(3,6-dioxaheptyl)amine (TDA-1) have been analyzed in reactions of alkoxydehalogenation of 2- and 4-chloropyridine and their N-oxides under solid-liquid phase transfer catalysis conditions. Alkoxypyridines were obtained in excelent yields but with N-oxides a competitive alkaline cleavage of the performed ether was observed.

Tetrahedron 01/1987; 43(11):2557–2564. · 2.82 Impact Factor

 

Source

Pyruvate decarboxylating action of L-cycloserine. The significance of this in understanding its metabolic inhibitory action.

D Pérez-Sala, S Cerdán, P Ballesteros, M S Ayuso, R Parrilla

ABSTRACT: We present evidence which demonstrates that L-cycloserine, structural analog of L-alanine, which is known to be an effective aminotransferase inhibitor, is also a potent inhibitor of cellular pyruvate metabolism. This effect was found to be related to its almost instantaneous action in decreasing pyruvate concentrations in a dose-dependent manner. 1H nuclear magnetic resonance studies clearly demonstrate that the irreversible removal of pyruvate induced by L-cycloserine is caused by the decarboxylating action of the latter. Pyruvate disappearance induced by L-cycloserine can be stoichiometrically accounted for as acetate. The process does not involve any chemically detected transformation of L-cycloserine. These observations lead to two main considerations regarding the known action of L-cycloserine. First, its inhibitory effect on gluconeogenesis from lactate could be explained only on the basis of its ability to reduce pyruvate availability with no apparent need for transaminase inhibition. Second, its ability as a transaminase inhibitor should be reconsidered in view of its potent decarboxylating action on pyruvate and probably other oxoacids.

Journal of Biological Chemistry 11/1986; 261(30):13969-72. · 4.60 Impact Factor

The structure of indazolinone and derivatives in the solid state and in solution: an X-ray and nuclear magnetic resonance study

Paloma Ballesteros, José Elguero, Rosa María Claramunt, Robert Faure, Ma de la Concepción Foces-Foces, Félix Hernández Cano,Albert Rousseau

ABSTRACT: The structure of indazolinone and some of its derivatives was obtained by the combined use of crystallography, 13C CP/MAS, and 15N n.m.r. It was concluded that indazolinone exists as such in the solid state but only as a minor tautomer (15%) in DMSO solution, where the 3-hydroxyindazole tautomer predominates (85%). The result of bromination of indazolinone is reported. Two acylhydrazines, as open analogues of indazolinone, were studied as model compounds.

Journal of the Chemical Society Perkin Transactions 2 01/1986;

Interception of [2+2] cycloadducts in the zinc bromide mediated reaction of di-tert-butyl methylenemalonate with simple enol ethers

Marsha R Baar, Paloma Ballesteros, Bryan W Roberts

ABSTRACT: Di–butyl methylenemalonate combines efficiently with simple enol ethers at -78°C in the presence of zinc bromide to give [2+2] cycloadducts.

Tetrahedron Letters 01/1986; 27(19):2083–2086. · 2.39 Impact Factor

Anti-influenza A activity of some N-substituted bicyclo[3.2.1]octane-3-spiro-3′-pyrrolidine hydrochlorides: synthesis and structure.

E de la Cuesta, P Ballesteros, G G Trigo

ABSTRACT: Some N-substituted bicyclo[3.2.1]octane-3-spiro-3′-pyrrolidine hydrochlorides (IX-XII) prepared from bicyclo[3.2.1]octan-3-one (I), were assayed in vitro against influenza A viruses. All materials showed activity similar to 1-adamantanamine hydrochloride. A 1H-NMR study revealed only one isomer at the spiro carbon atom.

Journal of Pharmaceutical Sciences 10/1984; 73(9):1307-9. · 3.01 Impact Factor

Anti-influenza a activity of someN-substituted bicyclo[3.2.1]octane-3-spiro-3′-pyrrolidine hydrochlorides: Synthesis and structure

Elena De La Cuesta, Paloma Ballesteros, Gregorio G. Trigo

ABSTRACT: Some N-substituted bicyclo[3.2.1]octane-3-spiro-3′-pyrrolidine hydrochlorides (IX-XII) prepared from bicyclo[3.2.1]octan-3-one (I), were assayed in vitro against influenza A viruses. All materials showed activity similar to I-adamantanamine hydrochloride. A 1H-NMR study revealed only one isomer at the spiro carbon atom.

Journal of Pharmaceutical Sciences 01/1984; 73(9):1307-1309. · 3.13 Impact Factor

Synthesis and transport applications of 3-aminobicyclo[3.2.1] octane-3-carboxylic acids.

H N Christensen, M E Handlogten, J V Vadgama, E de la Cuesta, P Ballesteros, G G Trigo, C Avendaño

ABSTRACT: The isomeric 3-aminobicyclo[3.2.1]octane-3-carboxylic acids were synthesized and compared with the widely used (1R,2S,4S)-2-aminobicyclo[2.2.1]heptane-2-carboxylic acid as to specificity to the Na+-independent membrane transport system L of the Ehrlich ascites tumor cell and of the rat hepatoma cell line HTC. The presence of an additional methylene group in the ring system leads to an optically symmetrical amino acid, with the advantages that the product is devoid of isomeric contamination. Hence, optical resolution is not necessary to secure a homogeneous test substrate for discrimination of amino acid transport systems. Through its inhibitory action on the cellular uptake of known system-specific amino acids, the bicyclo[3.2.1]octane amino acid proved more reactive than the bicycloheptane analogue with the Na+-independent amino acid transport system of the test cells and not perceptibly reactive with the accompanying Na+-dependent systems. Recent evidence of the presence of a second component of Na+-independent amino acid transport, beyond system L, increases the importance of securing a variety of possibly discriminatory model substrates.

Journal of Medicinal Chemistry 11/1983; 26(10):1374-8. · 5.48 Impact Factor

Synthesis of di-tert-butyl methylenemalonate, a sterically hindered 1,1-dicarbonyl alkene

Paloma Ballesteros, Bryan W. Roberts, Janice Wong

Journal of Organic Chemistry – J ORG CHEM. 01/1983; 48(20):3603-3605.

 

Paula Zaderenko, Pilar López, Paloma Ballesteros, Hideaki Takumi, Fumio Toda

ABSTRACT: Some racemic 2-imidazol-1-yl and 2-pyrazol-1-ylsuccinic esters, prepared by nucleophilic addition of the corresponding azole to fumaric esters, have been resolved. The enantioselective inclusion methodology has been applied using compounds derived from tartaric acid as chiral hosts.

Tetrahedron Asymmetry 02/1995; 6(2):381–384. · 2.17 Impact Factor

Alan R. Katritzky, Paloma Ballesteros, Alberto Tarraga Tomas

ABSTRACT: Literature data on the title reactions are reviewed and further examples given particularly with dialkylhydrazines and hydrazones. Compounds derived from 2-ethoxycarbonyl-4,6-diphenylpyrylium tend to cyclise and new examples of the dihydropyrazoloquinoline (27) and oxidopyrido[1,2-b]pyridazinium [(62)–(64)] ring systems are described.

Journal of the Chemical Society Perkin Transactions 1 01/1981; · 1.95 Impact Factor

  1. Bellanato, C. Avendaño, P. Ballesteros, E. de la Cuesta, E. Santos, G.G. Trigo

ABSTRACT: Five amino acids with known configuration: α- and β-3-amino-tropane- and 3-amino-bicyclo(3.2.1)octane-3-carboxylic acids and α -3-amino-granatane-3-carboxylic acid have been studied by i.r. and 1H NMR spectroscopy. Both α- and γ-zwitterion structures have been found for tropane and granatane amino acids. Equatorial and axial ammonium groups in α-zwitterions can be distinguished by the number and frequencies of the ammonium deformation modes. A chair—boat conformation has been deduced for α-3-amino-granatane-3-carboxylic acid.

Spectrochimica Acta Part A: Molecular Spectroscopy. 01/1981; 37(11):965–971.

  1. Bellanato, C. Avendaño, P. Ballesteros, E. Santos, G.G. Trigo

ABSTRACT: Infrared data of some granatanine-3-spiro-5′-hydantoins and tropane-3-spiro-5′-thiohydantoins revealed the ability of these compounds, to exist as zwitterion structures in the solid state.

Spectrochimica Acta Part A: Molecular Spectroscopy. 01/1980; 36(10):879–884.

  1. G. Trigo, C. Avendaño, P. Ballesteros, A. Sastre

Journal of Heterocyclic Chemistry – J HETEROCYCL CHEM. 01/1980; 17(1):103-105.

  1. G. Trigo, C. Avendaño, P. Ballesteros, A. Gonzalez

Journal of Heterocyclic Chemistry 08/1978; 15(5):833-837. · 0.87 Impact Factor

Paloma Ballesteros García, Pilar López-Larrubia, Laura Domínguez Mateo, José Luis Marco Contelles, Sebastián Cerdán García-Esteller

ABSTRACT: Referencia OEPM: P200300936 .– Fecha de solicitud: 23/04/2003.– Titulares: Universidad Nacional de Educación a Distancia (UNED), Consejo Superior de Investigaciones Científicas (CSIC). Un compuesto de Fórmula General A que se puede emplear como indicador extrínseco para la determinación de pH celular por espectroscopia e imagen de Resonancia Magnética. El compuesto de Fórmula General A en donde n es 1; n es 2; n es 3 y n es 4. Un procedimiento para la obtención del compuesto de Fórmula General A, de la reivindicación 1 que parte de los correspondientes alditoles e implica las etapas que se indican a continuación. 1. Protección selectiva de grupos OH primarios y secundarios; 2. Desprotección selectiva de grupos primarios y 3. Activación grupos OH primarios. Los intermedios activados de los alditoles se hacen reaccionar con 4 equivalentes de imidazol en medio básico para obtener los correspondientes derivados de imidazol. La desprotección final de los grupos OH secundarios conduce a los correspondientes 1,{oe}-di-imidazol-1-ilpolioles deseados. La utilización experimental y clínica del compuesto de Fórmula General A en el diagnóstico por imagen. Peer reviewed

  1. Bellanato, C. Avendaño, P. Ballesteros, M. Martinez

ABSTRACT: The i.r. spectra of two series of hydantoin spiro derivatives of nortropane and granatanine in the solid state have been studied in the NH and CO stretching regions. Absorption bands due to strong hydrogen bonds between the N3H group and the piperidine nitrogen atom have been observed in the 3000-1800 cm−1 region for almost all compounds. These hydrogen bonds have been confirmed by X-ray data and can be related to the piperidine nitrogen basicity and also to steric effects of the substituent on this nitrogen atom. The i.r. results in the carbonyl region have been compared with Raman data and are interpreted in terms of coupling effects.

Spectrochimica Acta Part A: Molecular Spectroscopy. 35(7):807–812.

Paloma Ballesteros García, M.ª Soledad Gil González, Paula Zaderenko Partida, Sebastián Cerdán García-Esteller, José Álvarez Pérez, Robert J Gillies, Raghumand Natarajan, Robert Van Sluis, Zaver Bhjwala

ABSTRACT: Referencia OEPM: P9700496.– Fecha de solicitud: 06/03/1997.– Titulares: Universidad Nacional de Educación a Distancia (UNED), Consejo Superior de Investigaciones Científicas (CSIC). Peer reviewed

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