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[3+2] cycloadditions of nitroolefins have emerged as a selective and catalyst-free alternative for the synthesis of 1,2,3-triazoles from azides. We describe mechanistic studies into the cycloaddition/rearomatization reaction sequence. DFT calculations revealed a rate-limiting cycloaddition step proceeding via an asynchronous TS with high kinetic selectivity for the 1,5-triazole. Kinetic studies reveal a second-order rate law, and 13C kinetic isotopic effects at natural abundance were measured with a significant normal effect at the conjugated olefinic centers of 1.0158 and 1.0216 at the α and β-carbons of β-nitrostyrene. Distortion/interaction-activation strain and energy decomposition analyses revealed that the major regioisomeric pathway benefits from an earlier and less-distorted TS, while intermolecular interaction terms dominate the preference for 1,5- over 1,4-cycloadducts. In addition, the major regioisomer also has more favorable electrostatic and dispersion terms. Additionally, while static DFT calculations suggest a concerted but highly asynchronous Ei-type HNO2 elimination mechanism, quasiclassical direct-dynamics calculations reveal the existence of a dynamic intermediate., R.S.P. acknowledges support from the NSF (CHE-1955876) and computational resources from the RMACC Summit supercomputer supported by the National Science Foundation (ACI-1532235 and ACI-1532236), the University of Colorado Boulder and Colorado State University, and the Extreme Science and Engineering Discovery Environment (XSEDE) through allocation TG-CHE180056. J.V.A.-R. acknowledges support from XSEDE through allocation TG-CHE200033. J.V.A.R. acknowledges financial support through a Juan de la Cierva Incorporación contract from the Ministry of Science and Innovation (MCIN) and the State Research Agency (AEI) of Spain, and the European Union (NextGenerationEU/PRTR) under grant reference IJC2020-044217-I. M.A.B.F., C.F.T., and M.Y.K. are grateful to CNPq (405052/2021-9) and FAPESP (17/01754-0, 20/10246-0, and 20/01255-6) for financial support. This study was financed in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior – Brasil (CAPES) – Finance Code 001.

The analysis of complex mixtures is an important but often intractable problem. When species contain sparse fluorine atoms, NMR spectra of fluorine-containing spin systems can be efficiently extracted from an intact mixture using the recently proposed FESTA (Fluorine-Edited Selective TOCSY Acquisition) methodology. Here an alternative approach to the existing selective reverse INEPT FESTA (SRI-FESTA) experiment is described, based on the use of a modulated spin echo for the initial excitation. MODO-FESTA (modulated echo FESTA) is simpler and has a significant sensitivity advantage over SRI-FESTA. Comparisons are presented of the relative sensitivity and spectral purity of the two types of methods.

The long-range scalar coupling constant between proton and fluorine nuclei, 5 JHF , is observed to be larger than 3 JHF in the pyrimidinyl moiety of voriconazole. A set of smaller molecules is chosen (fluorobenzene, N-methyl-2-fluoropyridine, N-methyl-3-fluoropyridine, 3-fluoropyridine, 5-pyrimidine, and 2-fluoropyridine) to evaluate the influence of the nitrogen atom in the experimental JHF values. Spectral aliased pure shift heteronuclear single quantum coherence spectroscopy (SAPS-HSQC) is applied to determine the relative sign between the JCF and JHF scalar couplings. Theoretical calculations show that the 3 JHF and 5 JHF coupling constants can be described mainly by a Fermi contact (FC) transmission mechanism. A decomposition analysis of JHF in terms of localized molecular orbital (LMO) contributions allows us to determine that the interaction involving the nitrogen lone pair (LPN) is the main reason for the larger 5 JHF compared to 3 JHF . Our analysis indicates that delocalization of LPN has a positive contribution to the long-range coupling, while a negative one is observed for 3 JHF .

In complex mixtures, proton nuclear magnetic resonance (NMR) spectra are often very crowded, making spectral analysis complicated or even impossible, particularly when detailed structural information about the mixture components is needed. A new 1D NMR method (fluorine-edited selective TOCSY acquisition, FESTA) is introduced that facilitates the structural analysis of mixtures of species that contain fluorine. It allows simplified 1H spectra to be obtained that show only those protons that are in a spin system coupled to fluorine of interest. The new method is illustrated by factorizing a complex 1H spectrum into subspectra for individual spin systems involving different 19F sites.

Agradecimentos: The authors acknowledge the Brazilian agencies CNPq (grant number: 301016/2015-1), FAPESP (grant numbers: 2015/ 25406-5 and 2015/08541-6), and PETROBRAS (grant number: 2015/00103-0). We also want to thank the lab technician of the Colloids and Interfaces Group of UNICAMP, Victor Augusto Licio Garcia Vilela, for helping to perform experiments (grant number: 301016/2015-1) and Marcelo Alexandre de Farias from the Brazilian Nanotechnology National Laboratory (LNNano) for the help in the CryoTEM analysis and also LNNano to the access to the CryoTEM facilities (research proposal: TEM-24274) Abstract: The energy released when tetradecyltrimethylammonium bromide (C14TAB) is combined with different derivatives of chlorobenzoates in an isothermal titration calorimeter (ITC) allows a direct evaluation of the spontaneity of the threading of the aromatic anions into the micellar palisade. The comparison between the enthalpimetric curves with the ones for viscosity of the solutions, hydrodynamic radii of the aggregates (dynamic light scattering experiments), and the fraction of aromatic anions incorporated (diffusion-ordered spectroscopy experiments) allows the establishment of the variations of enthalpy with formation, growth, and decrease of the wormlike micelles (WLMs). The formation of WLMs with C14TAB is very favored (very exothermic) for titrations of chlorobenzoate derivatives which present the chlorine atom in positions 3 or 4 of the aromatic ring. However, the aggregation is highly unfavorable if chlorine is at position 2 of chlorobenzoate. According to the results, the high potential of the ITC to determine critical concentrations and the energies associated with the aggregation of a cationic surfactant and aromatic anions for the formation of WLMs was demonstrated FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESP CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQ Fechado

The guanine base in DNA, due to its low oxidation potential, is particularly sensitive to chemical modifications. A large number of guanine lesions have been characterized and studied in some detail due to their relationship with tissue inflammations. Nevertheless, one example of these lesions is the formation of 8-nitro-guanosine, but the NMR data of this compound was only partially interpreted. A comprehensive study of the two possible tautomeric forms, through a detailed characterization of this compound, has implications for its base pairing properties. The target compound was obtained through a synthetic sequence of five steps, where all intermediates were fully characterized using spectral data. The analysis of the two tautomers was then evaluated through NMR spectroscopy and theoretical calculations of the chemical shifts and NH coupling constants, which were also compared with the data from guanosine.

The long-range scalar coupling constant between proton and fluorine nuclei

Conformational isomerism in trans-3-X-2-hydroxy-tetrahydropyrans (X = F, Cl, Br, I) was investigated by NMR spectroscopy and electronic structure calculations. The compounds were synthesized, purified and identified by 1H, 13C and selective TOCSY NMR spectra and by HSQC, COSY and NOESY contour maps. The geometries and conformer energies for the most stable conformers in the isolated molecules were calculated using M06-2X hybrid functional (DFT) and MP2 (ab initio) methods with the aug-cc-pVTZ basis set. Theoretical calculations taking into account the solvent effect (CHCl3 and DMSO) were performed using the IEFPCM solvent model, M06-2X/aug-cc-pVTZ level of theory for C, H and O atoms and M06-2X/aug-cc-pVDZ-PP with pseudopotential for the iodine atom. NBO, QTAIM and NCI analyses were applied to identify which stereoelectronic interactions are responsible for their conformational preferences. The conformer stability changes in the presence of solvent. The anomeric effect does not appear to have a significant influence on the molecular conformations in these molecules.

Stress tests form an important part of drug development, and of subsequent accreditation. Commonly the change in chemical composition over time is determined using chromatographic methods that separate the mixture components, but when structural characterization of the degradation products is required, other methods are needed. Arguably the most powerful method for determining chemical structure information is NMR spectroscopy. Here we show that NMR alone, using a combination of simple 19F, 1H, and DOSY experiments, can characterise both structure and kinetics of an intact reaction mixture, without the need for any physical separation.

Suitable (3)J(H,H) coupling constants and theoretical calculations were used to define the conformational preferences of trans-2-bromoalkoxycyclohexanes (alkoxy = OMe, OEt, O(i)Pr, and O(t)Bu) for the isolated molecule and as a function of the medium. The diaxial conformer was preponderant, or at least similarly populated to the diequatorial form, for the tert-butoxy derivative only, while the diequatorial conformer was prevalent for the remaining alkoxy derivatives (except for the OMe derivative in CCl(4) solution). The conformational behavior of these compounds was analyzed on the basis of classical steric effects and attractive electron delocalizations, by means of natural bond orbital analysis.

The conformational preferences of 3-hydroxytetrahydropyran (1) were evaluated using infrared and nuclear magnetic resonance spectroscopic data in solvents of different polarities. Theoretical calculations in the isolated phase and including the solvent effect were performed, showing that the most stable conformations for compound 1 are those containing the substituent in the axial and equatorial orientations. The axial conformation is more stable in the isolated phase and in a nonpolar solvent, while the equatorial conformation is more stable than the axial in polar media. The occurrence of intramolecular hydrogen-bonded O–H···O in the axial conformer was detected from infrared spectra in a nonpolar solvent at different concentrations. Our attempt to evaluate this interaction using population natural bond orbital and topological quantum theory of atoms in molecules analyses failed, but topological noncovalent interaction analysis was capable of characterizing it.

In this work, a new approach to studying coupling pathways for the Fermi contact term of NMR spin-spin coupling constants (SSCCs) is presented. It is based on the known form of propagating the Fermi hole through a canonical molecular orbital (CMO). It requires having an adequate spatial description of the relevant canonical molecular orbitals, which are obtained by expanding CMOs in terms of natural bond orbitals (NBOs). For detecting the relevant contributions of CMOs to a given Fermi contact (FC) pathway, the description of the FC in terms of the triplet polarization propagator (PP) is used. To appreciate the potential of this approach, dubbed FCCP-CMO (Fermi contact coupling pathways-CMO), it is applied to analyze the through-space transmission of the FC term of JPP SSCCs by overlap of the P lone pairs. This method can be applied using well-known quantum chemistry software without any further modification, which makes it appealing for use as a complement to SSCC measurements by NMR spectroscopy. © 2010 American Chemical Society. Fil: Contreras, Ruben Horacio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Física de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Física de Buenos Aires; Argentina Fil: Gotelli, Gustavo A.. Universidad de Buenos Aires; Argentina Fil: Ducati, Lucas C.. Universidade Estadual de Campinas; Brasil Fil: Barbosa, Thais M.. Universidade Estadual de Campinas; Brasil Fil: Tormena, Cláudio F.. Universidade Estadual de Campinas; Brasil