Search

The halogen bond is a powerful tool for the molecular design and pushing the limits of its strength is of major interest. Bearing the most potent halogen-bond donor atom, astatine monoiodide (AtI) was recently successfully probed [Nat. Chem. 2018, 10, 428-434]. In this work, we continue the exploration of adducts between AtI and Lewis bases with the tributylphosphine oxide (Bu 3 PO) ligand, revealing the unexpected experimental occurrence of two distinct chemical species with 1:1 and 2:1 stoichiometries. The 1:1 Bu 3 PO⋅⋅⋅AtI complex is found to exhibit the strongest astatine-mediated halogen bond so far (with a formation constant of 10 (4.24±0.35) ). Quantum chemical calculations unveil the intriguing nature of the 2:1 2Bu 3 PO⋅⋅⋅AtI adduct, involving a halogen bond between AtI and one Bu 3 PO molecular unit plus CH⋅⋅⋅O hydrogen bonds chelating the second Bu 3 PO unit., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Rational modulations of molecular interactions are of significant importance in compound properties optimization. We have previously shown that fluorination of conformationally rigid cyclohexanols leads to attenuation of their hydrogen-bond (H-bond) donating capacity (designated by pK AHY ) when OH⋅⋅⋅F intramolecular hydrogen-bond (IMHB) interactions occur, as opposed to an increase in pK AHY due to the fluorine electronegativity. This work has now been extended to a wider range of aliphatic β-fluorohydrins with increasing degrees of conformational flexibility. We show that the observed differences in pK AHY between closely related diastereomers can be fully rationalized by subtle variations in populations of conformers able to engage in OH⋅⋅⋅F IMHB, as well as by the strength of these IMHBs. We also show that the Kenny theoretical V α (r) descriptor of H-bond acidity accurately reflects the observed variations and a calibration equation extended to fluorohydrins is proposed. This work clearly underlines the importance of the weak OH⋅⋅⋅F IMHB in the modulation of alcohol H-bond donating capacity., (© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Evidencing new chemical species in solution is particularly challenging when one works at ultra-trace concentrations, as is likely to happen with radioelements such as astatine (Z=85). Herein, quantum mechanical calculations were used to predict the narrow experimental domain in which it is possible to detect the presence of an exotic ternary trihalogen anion, IAtBr - , and thus to guide a series of experiments. By analyzing the outcomes of competition experiments, we show that IAtBr - exists and can even predominate in aqueous solution. The equilibrium constant associated with the reaction At + +I - +Br - ⇌IAtBr - was determined to be 10 7.5±0.2 , which is in fair agreement with that predicted by density functional theory (10 6.9 ). This system not only constitutes the very first example of a ternary trihalogen species that involves the element astatine but is also the first trihalogen species reported to predominate in solution. Moreover, we show that the oxidation number of At is zero in this species, as in the other molecules and anions that At + can form with Cl - , Br - , and I - ligands., (© 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

It is generally assumed that astatide (At(-) ) is the predominant astatine species in basic aqueous media. This assumption is questioned in non-complexing and non-reductive aqueous solutions by means of high-pressure anion-exchange chromatography. Contrary to what is usually believed, astatide is found to be a minor species at pH=11. A different species, which also bears a single negative charge, becomes predominant when the pH is increased beyond 7. Using competition experiments, an equilibrium constant value of 10(-6.9) has been determined for the formation of this species from AtO(OH) with the exchange of one proton. The identification of this species, AtO(OH)2 (-) , is achieved through relativistic quantum mechanical calculations, which rule out the significant formation of the AtO2 (-) species, while leading to a hydrolysis constant of AtO(OH) in excellent agreement with experiment when the AtO(OH)2 (-) species is considered. Beyond the completion of the Pourbaix diagram of astatine, this new information is of interest for the development of (211) At radiolabeling protocols., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Fluorination is commonly exercised in compound property optimization. However, the influence of fluorination on hydrogen-bond (HB) properties of adjacent functional groups, as well as the HB-accepting capacity of fluorine itself, is still not completely understood. Although the formation of OH⋅⋅⋅F intramolecular HBs (IMHBs) has been established for conformationally restricted fluorohydrins, such interaction in flexible compounds remained questionable. Herein is demonstrated for the first time-and in contrast to earlier reports-the occurrence of OH⋅⋅⋅F IMHBs in acyclic saturated γ-fluorohydrins, even for the parent 3-fluoropropan-1-ol. The relative stereochemistry is shown to have a crucial influence on the corresponding (h1) JOH⋅⋅⋅F values, as illustrated by syn- and anti-4-fluoropentan-2-ol (6.6 and 1.9 Hz). The magnitude of OH⋅⋅⋅F IMHBs and their strong dependence on the overall molecular conformational profile, fluorination motif, and alkyl substitution level, is rationalized by quantum chemical calculations. For a given alkyl chain, the "rule of shielding" applies to OH⋅⋅⋅F IMHB energies. Surprisingly, the predicted OH⋅⋅⋅F IMHB energies are only moderately weaker than these of the corresponding OH⋅⋅⋅OMe. These results provide new insights of the impact of fluorination of aliphatic alcohols, with attractive perspectives for rational drug design., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The effect of fluorination on the conformational and hydrogen-bond (HB)-donating properties of a series of benzyl alcohols has been investigated experimentally by IR spectroscopy and theoretically with quantum chemical methods (ab initio (MP2) and DFT (MPWB1K)). It was found that o-fluorination generally resulted in an increase in the HB acidity of the hydroxyl group, whereas a decrease was observed upon o,o'-difluorination. Computational analysis showed that the conformational landscapes of the title compounds are strongly influenced by the presence of o-fluorine atoms. Intramolecular interaction descriptors based on AIM, NCI and NBO analyses reveal that, in addition to an intramolecular OH⋅⋅⋅F interaction, secondary CH⋅⋅⋅F and/or CH⋅⋅⋅O interactions also occur, contributing to the stabilisation of the various conformations, and influencing the overall HB properties of the alcohol group. The benzyl alcohol HB-donating capacity trends are properly described by an electrostatic potential based descriptor calculated at the MPWB1K/6-31+G(d,p) level of theory, provided solvation effects are taken into account for these flexible HB donors., (© 2015 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.)

Structural features of galanthamine and codeine, two allosteric potentiating ligands of nicotinic acetylcholine receptors (nAChRs), have been investigated through experimental studies in solution by FTIR and NMR spectroscopy and by quantum chemical calculations in the isolated state. The infrared spectra accumulated in solvents of various polarities show that the intramolecular OH···O hydrogen bond in galanthamine is stronger than the corresponding interaction in codeine. Molecular electrostatic potential calculations allow rationalisation of the experimental trends. NOE measurements on the two ligands in the same solvent range show significant differences. In apolar solvents, the NMR spectroscopic data indicate the occurrence of CH···O hydrogen-bond interactions, whereas in the more polar solvents, a trans orientation of the methoxy group with respect to the furanyl oxygen atom is favoured. A natural bond orbital (NBO) analysis provides evidence that these stabilising interactions originate in the hyperconjugation between the lone pairs of the furanyl oxygen atoms, n(O), and the methoxy antibonding σ*(C-H) orbitals within the two molecules. Despite the strong structural similarities between the two allosteric modulators, FTIR equilibrium constants measurements of hydrogen-bond complexation combined with quantum chemistry calculations point out the significant increase of hydrogen-bond accepting strength of galanthamine relative to codeine. This increase is mainly assignable to the stronger hydrogen-bond basicity of the hydroxyl group, and to a lesser extent to the higher hydrogen-bond accepting strength of the amino nitrogen of galanthamine in comparison with the corresponding groups of codeine. An analysis of the interactions that occur between the two ligands and acetylcholine esterase (AChE) suggests significant differences with Trp84, a key component of the AChE catalytic active site. In contrast, both ligands appear to interact similarly with acetylcholine binding protein (AChBP)., (Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)