A Spectroscopic study of colchicine in the solid state and in solution by multinuclear magnetic resonance and vibrational circular dichroism

Although almost 200-years-old, several unknown aspects remain to be explored of colchicine, the unique available drug for acute flares of gout. In this article, we report density-functional theory (DFT) studies of geometry, energy, and NMR; 1H-, 13C-, and 15N-NMR chemical shifts and some spin-spin coupling constants, including the complete analysis of the saturated part (ring B); the assignment of both enantiomers by NMR using a chiral solvating agent; solid-state NMR experiments of the different forms of natural and racemic colchicine, and IR and vibrational circular dichroism (VCD) studies of these same forms. Copyright © 2014 Verlag Helvetica Chimica Acta AG, Zürich.Peer Reviewe

On the ionophoric selectivity of nonactin and related macrotetrolide derivatives

Nonactin and its analogs constitute a central class of macrocycles with an antibiotic activity closely related to their selective ionophoric behavior. In this study, we apply experimental and computational methods to revisit the specificity of cation binding and transport by three nactin variants differing in structural properties, such as the position of the ester linkages, the nature of the side groups, or the flexibility of the backbone. On the one hand, electrospray ionization mass spectrometry and infrared spectroscopy are employed to expose the selectivity of the liquid-liquid (water-chloroform) extraction of alkali cations by nonactin and to demonstrate that the cation complexes are partially hydrated in the organic phase. Furthermore, laser desorption mass spectrometry is employed to determine the intrinsic cation affinities of nonactin under solvent-free conditions. On the other hand, density functional theory calculations are performed to characterize the conformations of the alkali cation complexes of the three nactins, and to assess the role of intermolecular and solvent interactions in determining their relative stability. Depending on the structure of the macrocycle, the cation complexes adopt either a cage-like conformation or a tweezer-like conformation. The computations show that the partial hydration of those different conformations in the organic phase, determine the distinct cation extraction selectivities that are observed experimentally.We would like to acknowledge financial support from the government of Spain (Projects CSD2009-00038 and CTQ2015-63997-C2-2-P), and from the regional Research Programmes of Junta de Andalucía FEDER (Project P12-FQM-2310) and of Comunidad Autonoma de Madrid (S2013/MIT-2841, Fotocarbon).Peer Reviewe

Carbohydrates in the gas phase: Conformational preference of D-ribose and 2-deoxy-D-ribose

A full exploration of the conformational landscape of d-ribose and 2-deoxy-d-ribose monosaccharides in the gas phase has been performed using DFT methods (B3LYP and M06-2X). Open-chain, furanose and pyranose configurations have been examined. Up to 954 and 668 stable structures have been obtained for d-ribose and 2-deoxy-d-ribose. Among these structures, up to 35 and 22 have relative energies smaller than 5 kJ mol-1 with respect to the absolute minimum of each molecule, respectively. For d-ribose, pyranose in α- and β-forms is the most populated according to both functionals, the β-diastereoisomer being the most populated. For 2-deoxy-d-ribose, the α-pyranose form is in majority. The β/α relationship of pyranose forms presents different results for both functionals: for M06-2X it increases in d-ribose and decreases in 2-deoxy-d-ribose at 0 K with respect to the room temperature results, the opposite case occurring in B3LYP. Intramolecular weak interactions have been characterized using the AIM and NBO methodologies. © 2014 The Royal Society of Chemistry and the Centre National de la Recherche Scientifique.Peer Reviewe

Conformational preference and chiroptical response of Carbohydrates D-Ribose and 2-Deoxy-D-ribose in aqueous and solid phases

This work targets the structural preferences of D-ribose and 2-deoxy-D-ribose in water solution and solid phase. A theoretical DFT (B3LYP and M06-2X) and MP2 study has been undertaken considering the five possible configurations (open-chain, a-furanose, β-furanose, a-pyranose, and β-pyranose) of these two carbohydrates with a comparison of the solvent treatment using only a continuum solvation model (PCM) and the PCM plus one explicit water molecule. In addition, experimental vibrational studies using both nonchiroptical (IR-Raman) and chiroptical (VCD) techniques have been carried out. The theoretical and experimental results show that a- and β-pyranose forms are the dominant configurations for both compounds. Moreover, it has been found that 2-deoxy-D-ribose presents a non-negligible percentage of open-chain forms in aqueous solution, while in solid phase this configuration is absent.© 2013 American Chemical Society.Peer Reviewe

Understanding the Aldo-Enediolate Tautomerism of Glycolaldehyde in Basic Aqueous Solutions

The biochemically important interconversion process between aldoses and ketoses is assumed to take place via 1,2-enediol or 1,2-enediolate intermediates, but such intermediates have never been isolated. The current work was undertaken in an attempt to detect the presence of the 1,2-enediol structure of glycolaldehyde in alkaline medium, actually a 1,2-enediolate, and to try to clarify the scarce data existing about both the formation of deprotonated enediol and the aldo-enediolate equilibrium. The Raman spectra of neutral and basic solutions were recorded as a function of time for eleven days. Several bands associated with the presence of the enediolate were observed in alkaline medium. Glycolaldehyde exists as three different structures in aqueous solution at neutral pH, that is, hydrated aldehydes, aldehydes and dimers, with a respective ratio of approximately 4:0.25:1. Additionally, the formation of Z-enediolate forms takes place at basic pH, together with an increase in the concentration of aldehyde species, such as 2-oxoethan-1-olate, and a decrease in the concentrations of the hydrated aldehyde and dimeric forms. The theoretical ratio of ≈1.5:1 for aldehyde:Z-enediolate reproduces the experimental Raman spectrum in basic medium, with an additional contribution of the previously mentioned ratio between the hydrated aldehyde and dimeric forms. Finally, Raman spectroscopy allowed us to monitor the enolization of this carbohydrate model and conclude that aldo-enediol tautomerism - formally aldo-enediolate - happens when a suitable amount of basic species is added.LMA thanks the MICINN for a PhD grant (No. BES-2010-031225). MMQM thanks the Universidad de Jaén for a predoctoral fellowship. This work has been supported by the CTQ2012-35513-C02- 02 (MINECO), P08-FQM-04096 (CICE, Junta de Andalucía) and S2013/MIT-2841 (Fotocarbon, Comunidad Autûnoma de Madrid) Projects. Computer, storage and other resources from CTI (CSIC) are gratefully acknowledged. Gratitude is also due to the University of Jaén for continuing financial support and to its CICT for instrumental facilities. The authors also thank D. Francisco Hermoso Torres for his help in the laboratoryPeer Reviewe

Chiral self-assembly of enantiomerically pure (4S,7R)-campho[2,3-c]pyrazole in the solid state: A vibrational circular dichroism (VCD) and computational study

NH-Indazoles in solid phase usually form NHN hydrogen bonds between positions 1 and 2, which determine the secondary structure, forming dimers, trimers, or catemers (chains). Thus, the difficulty of the experimental analysis of the structure of the family of 1H-indazoles is clear. We have outlined a complete strategy by using different techniques of vibrational spectroscopy that are sensitive (VCD) and not sensitive (IR, FarIR, and Raman) to the chirality together with quantum chemical calculations. We have studied the chiral structure of (4S,7R)-campho[2,3-c]pyrazole both in solution (CCl4) and in the solid phase (crystal). This compound crystallizes as a chiral trimer (LABHEB), with the monomer also being chiral. Herein, Far-IR, IR, and Raman spectra in solution and in the solid state are assigned using the support of B3LYP/6-31G(d) and B97D/6-31+G(d,p) calculations of (4S,7R)-campho[2,3-c] pyrazole monomers, dimers, and trimers, these last cyclamers being partially and fully optimized. Later, analysis of the vibrational circular dichroism (VCD) spectra allowed us to determine the chiral self-assembly of (4S,7R)-campho[2,3- c]pyrazole crystals (LABHEB). In the crystal, only the trimers are present while in solution, the monomer predominates. We have highlighted the importance of the analysis of the low frequency region (700-25 cm-1) in the FT-Raman and Far-IR spectra, because it provides relevant information in order to confirm the presence of the trimers in the solid phase. © 2014 Elsevier Ltd. All rights reserved.Peer Reviewe

Self-assembly structures of 1H-indazoles in the solution and solid phases: A vibrational (IR, FIR, Raman, and VCD) Spectroscopy and computational study

1H-indazoles are good candidates for studying the phenomena of molecular association and spontaneous resolution of chiral compounds. Thus, because the 1H-indazoles can crystallize as dimers, trimers, or catemers, depending on their structure and the phase that they are in, the difficulty in the experimental analysis of the structure of the family of 1H-indazoles becomes clear. This difficulty leads us to contemplate several questions: How can we determine the presence of different structures of a given molecular species if they change according to the phase? Could these different structures be present in the same phase simultaneously? How can they be determined? To shed light on these questions, we outline a very complete strategy by using various vibrational spectroscopic techniques that are sensitive (VCD) and insensitive (IR, FIR, and Raman) towards the chirality, together with quantum chemical calculations. Spontaneous chiral resolution: 1H-indazoles are good candidates for studying the molecular association and spontaneous resolution of chiral compounds. These compounds can crystallize as dimers, trimers, or catemers, depending on their structure and phase. Various vibrational spectroscopy techniques that are sensitive (VCD) and insensitive (IR, FIR, and Raman) towards the chirality are employed, together with quantum chemical calculations. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.Peer Reviewe