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

Nurses' perceptions of aids and obstacles to the provision of optimal end of life care in ICU

Contains fulltext : 172380.pdf (publisher's version ) (Open Access

CARB-ES-19 Multicenter Study of Carbapenemase-Producing Klebsiella pneumoniae and Escherichia coli From All Spanish Provinces Reveals Interregional Spread of High-Risk Clones Such as ST307/OXA-48 and ST512/KPC-3

ObjectivesCARB-ES-19 is a comprehensive, multicenter, nationwide study integrating whole-genome sequencing (WGS) in the surveillance of carbapenemase-producing K. pneumoniae (CP-Kpn) and E. coli (CP-Eco) to determine their incidence, geographical distribution, phylogeny, and resistance mechanisms in Spain.MethodsIn total, 71 hospitals, representing all 50 Spanish provinces, collected the first 10 isolates per hospital (February to May 2019); CPE isolates were first identified according to EUCAST (meropenem MIC > 0.12 mg/L with immunochromatography, colorimetric tests, carbapenem inactivation, or carbapenem hydrolysis with MALDI-TOF). Prevalence and incidence were calculated according to population denominators. Antibiotic susceptibility testing was performed using the microdilution method (EUCAST). All 403 isolates collected were sequenced for high-resolution single-nucleotide polymorphism (SNP) typing, core genome multilocus sequence typing (cgMLST), and resistome analysis.ResultsIn total, 377 (93.5%) CP-Kpn and 26 (6.5%) CP-Eco isolates were collected from 62 (87.3%) hospitals in 46 (92%) provinces. CP-Kpn was more prevalent in the blood (5.8%, 50/853) than in the urine (1.4%, 201/14,464). The cumulative incidence for both CP-Kpn and CP-Eco was 0.05 per 100 admitted patients. The main carbapenemase genes identified in CP-Kpn were blaOXA–48 (263/377), blaKPC–3 (62/377), blaVIM–1 (28/377), and blaNDM–1 (12/377). All isolates were susceptible to at least two antibiotics. Interregional dissemination of eight high-risk CP-Kpn clones was detected, mainly ST307/OXA-48 (16.4%), ST11/OXA-48 (16.4%), and ST512-ST258/KPC (13.8%). ST512/KPC and ST15/OXA-48 were the most frequent bacteremia-causative clones. The average number of acquired resistance genes was higher in CP-Kpn (7.9) than in CP-Eco (5.5).ConclusionThis study serves as a first step toward WGS integration in the surveillance of carbapenemase-producing Enterobacterales in Spain. We detected important epidemiological changes, including increased CP-Kpn and CP-Eco prevalence and incidence compared to previous studies, wide interregional dissemination, and increased dissemination of high-risk clones, such as ST307/OXA-48 and ST512/KPC-3

Conformational Flexibility of Limonene Oxide Studied By Microwave Spectroscopy

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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

A vibrational circular dichroism (VCD) methodology for the measurement of enantiomeric excess in chiral compounds in the solid phase and for the complementary use of NMR and VCD techniques in solution: The camphor case

For the first time, the success of a methodology for the determination of enantiomeric excess (% ee) in chiral solid samples by vibrational circular dichroism (VCD) spectroscopy is reported. We have used camphor to determine the % ee in a blind sample constituted by a mixture of its two enantiomers as a test for the validity of our approach. IR and VCD spectra of different enantiomeric mixtures of R/S-camphor in Nujol mulls were recorded and linear regressions of VCD intensities (ΔAbs.) vs. % ee for selected bands were found. Finally, the VCD intensities of a blind sample were interpolated in these linear regressions, obtaining its % ee with a rms of 2.4. These results in the solid phase were complemented with the determination of % ee in the liquid phase by VCD and NMR techniques, which are proved to be complementary techniques to carry out this kind of analysis. In the same way as in the VCD solid phase, linear regressions of ΔAbs. vs. % ee for selected bands were established, obtaining a rms of 1.1 in the % ee determination of a blind sample. H NMR experiments at 600 MHz using the chiral solvating agent, (S,S)-ABTE, allow the determination of the proportions of enantiomers in CDCl solution with great accuracy. C CPMAS NMR spectra prove that this technique cannot be used for conglomerates and/or solid solutions.This work was carried out with financial support from the Ministerio de Economía y Competitividad (Project No. CTQ2012-32436, CTQ2014-56833-R and CTQ2015-63997-C2-2- P), CICE/JA-FEDER-UJA:Plan de Fortalecimiento de las Capacidades de I+D+i/2014–15 (UJA2013/08/03) and Comunidad Autónoma de Madrid (Project FOTOCARBON, ref. S2013/MIT-2841). Authors thank the University of Jaén for continuing financial support, for bridge projects (UJA2015/08/07 and UJA2016/08/15), for Acción 2: Financiación de Incentivos a la Excelencia de I+D+i de la UJA 2014–15 in 2014 and 2015 calls and to its CICT for instrumental facilities. M. M. Q. M. thanks the University of Jaén for both pre- and post-doctoral fellowships. We also thank the Servei de Ressonància Magnètica Nuclear, Universitat Autònoma de Barcelona, for allocating instrument time to this projectPeer Reviewe

Supramolecular organization of perfluorinated 1H-indazoles in the solid state using X-ray crystallography, SSNMR and sensitive (VCD) and non sensitive (MIR, FIR and Raman) to chirality vibrational spectroscopies

1H-Indazole derivatives exhibit a remarkable property since some of them form chiral supramolecular structures starting from achiral monomers. The present work deals with the study of three perfluorinated 1H-indazoles that resolve spontaneously as conglomerates. These conglomerates can contain either a pure enantiomer (one helix) or a mixture of both enantiomers (both helices) with an enantiomeric excess (e.e.) of one of them. The difficulty of the structural analysis of these types of compounds is thus clear. We outline a complete strategy to determine the structures and configurations (M or P helices) of the enantiomers (helices) forming the conglomerates of these perfluorinated 1H-indazoles based on X-ray crystallography, solid state NMR spectroscopy and different solid state vibrational spectroscopies that are either sensitive (VCD) or not (FarIR, IR and Raman) to chirality, together with quantum chemical calculations (DFT).This work was carried out with financial support from the Ministerio de Economía y Competitividad (Project No. CTQ2014- 56833R and CTQ2015-63997-C2-2-P), CICE/Junta de Andalucía (P08-FQM-04096) and CICE/JA-FEDER-UJA: Plan de Fortalecimiento de las Capacidades de I+D+i/2014-15 (UJA2013/08/03) and Comunidad Autónoma de Madrid (Project FOTOCARBON, ref. S2013/MIT-2841). Computer, storage and other resources from the CTI (CSIC) are gratefully acknowledged. Authors thank the University of Jaén for continuing financial support, for bridge projects (UJA2015/08/07) and (UJA2016/08/15) and for Accion 2: Financiacion de Incentivos a la Excelencia de I+D+i de la UJA 2014-15 in 2014 and 2015 calls and to its CICT for instrumental facilities. Authors also thank the FQM-323 research group, especially Rafael Lopez Blanco, David Moreno Gonzalez and Jose Robles Molina, for their help in the laboratory. M. M. Q. M. thanks the University of Jaen for a pre-doctoral fellowship. The CNRS is acknowledged for supportPeer Reviewe

The synergy of different solid-state techniques to elucidate the supramolecular assembly of two 1: H -benzotriazole polymorphs

1H-Benzotriazole crystallizes as two different polymorphs, namely 4aα and 4aβ. One polymorph is chiral and it resolves spontaneously as conglomerates. The other polymorph crystallizes in a centrosymmetric space group and it is therefore achiral. In both polymorphs supramolecular structures are formed starting from achiral monomers. An analysis of these two polymorphs of 1H-benzotriazole has been carried out by a complete strategy involving different solid-state experimental techniques and quantum chemical calculations (DFT, Density Functional Theory). In particular, X-ray crystallography, NMR spectroscopy and vibrational spectroscopy techniques (FarIR, IR and Raman) that are not sensitive to chirality have been used to characterize the two polymorphs structurally. Vibrational spectroscopy (VCD, Vibrational Circular Dichroism) that is sensitive to chirality was employed to determine the absolute configuration (M or P helices) of the chiral supramolecular structure of 4aα.The authors thank Professor Maria Gdaniec (Adam Mickiewicz University, Poznan´, Poland) for providing the so-called ‘commercial sample’ (the b form). This work was carried out with financial support from the Spanish Ministerio de Ciencia, Innovación y Universidades (Project No. CTQ2015-63997-C2-2-P and RTI2018- 097416-B-C21), CICE/Junta de Andalucía (P08-FQM-04096) and CICE/JA-FEDER-UJA: Plan de Fortalecimiento de las Capacidades de I+D+i/2014-15 (UJA2013/08/03) and Comunidad Autónoma de Madrid (Project FOTOCARBON, ref. S2013/MIT-2841). Computer, storage and other resources from the CTI (CSIC) are gratefully acknowledged. The authors thank the University of Jae´n for continuing financial support, for bridge projects (UJA2015/08/07 and UJA2016/08/15), for Accio´n 2: Financiacio´n de Incentivos a la Excelencia de I+D+i de la UJA 2014-15 in 2014 and 2015 calls and to its CICT for instrumental facilities. M.M.Q.M. thanks the University of Jaén for both pre- and post-doctoral fellowships.Peer Reviewe