Alessandro Bagno

Arzanol (1) exemplifies a large number of heterodimeric bioactive natural products based on an alkylidene‐bridged β‐dicarbonyl‐acylphloroglucinyl structural motif. The NMR spectra of these compounds are complicated by tautomeric and rotational equilibria that, despite growing synthetic and biomedical interest in the area, have not been systematically investigated. By combining information from NMR spectroscopy and DFT calculations, we have comparatively characterized the solution structures and conformations of the anti‐inflammatory agent arzanol (1), its inactive monomethyl derivative 4, and its corresponding homodimers [helipyrone (5) and demethylmallotojaponin C (6)]. The results highlight the relevance of a network of intramolecular hydrogen bonds for the tautomeric and rotameric equilibria of these compounds, with arzanol (1) existing in two almost equally populated rotameric forms of a 2‐pyrone tautomer, and its phloroglucinyl homodimer 6 in four major forms. Conversely, the monomethyl derivative 4 of arzanol and its dipyrone homodimer 5 exist in essentially a single solution form. Interestingly, this conformational bias was associated with a marked decrease of bioactivity.

Determining the stereochemistry of organic molecules is a long‐standing problem, with implications for stereoselective reactions, catalysis, and the structure of natural products. NMR spectroscopy is widely employed to this purpose; however, the interpretation of results is often entrusted to empirical methods or expert systems. Quantum chemical calculations, generally based on density functional theory, provide a reliable framework to predict the relevant parameters (chemical shifts and coupling constants, generally involving ¹H and ¹³C) of diastereoisomers with useful accuracy. While the approach virtually spans all molecules of interest in organic chemistry, including those that contain heavy atoms, the analysis of results still poses significant challenges. WIREs Comput Mol Sci 2015, 5:228–240. doi: 10.1002/wcms.1214This article is categorized under: Structure and Mechanism > Reaction Mechanisms and Catalysis Electronic Structure Theory > Density Functional Theory Theoretical and Physical Chemistry > Spectroscopy

The ¹⁷O NMR spectrum of the non‐coordinated carboxyl oxygen in the Gd^III–DOTA (DOTA=tetraazacyclododecanetetraacetic acid) complex has been observed experimentally. Its line width is essentially unaffected by paramagnetic relaxation due to gadolinium, and is only affected by the quadrupole pathway. The results are supported by the relevant parameters (hyperfine and quadrupole coupling constants) calculated by relativistic DFT methods. This finding opens up new avenues for investigating the structure and reactivity of paramagnetic Gd^III complexes used as contrast agents in magnetic resonance imaging.

DFT calculations allow to model and predict ¹⁹ F NMR chemical shift in a wide variety of organofluorine molecules.

The spin state of paramagnetic iron complexes can be predicted through the different ¹H NMR spectral patterns provided by DFT calculations.

We have investigated the structure and nuclear magnetic resonance (NMR) spectroscopic properties of some dihydrogen endofullerene nitroxides by means of density-functional theory (DFT) calculations. Quantum versus classical roto-translational dynamics of H₂have been characterized and compared. Geometrical parameters and hyperfine couplings calculated by DFT have been input to the Solomon–Bloembergen equations to predict the enhancement of the NMR longitudinal relaxation of H₂due to coupling with the unpaired electron. Estimating the rotational correlation time via computed molecular volumes leads to a fair agreement with experiment for the simplest derivative; the estimate is considerably improved by recourse to the calculation of the diffusion tensor. For the other more flexible congeners, the agreement is less good, which may be due to an insufficient sampling of the conformational space. In all cases, relaxation by Fermi contact and Curie mechanisms is predicted to be negligible.

The enzyme thioredoxin reductase (TrxR) is attracting much interest as a potential target for cancer therapy. The presence of a selenium atom in the catalytic site makes it sensitive to inhibition by electrophilic molecules, including the Au^I complex auranofin [2,3,4,6‐tetra‐O‐acetyl‐1‐thio‐β‐D‐glucopyranosato‐S‐(triethylphosphane)gold]. The reactions between auranofin and models of thiol and selenol nucleophiles present in TrxR (PhSH and PhSeH) have been investigated in chloroform and methanol by means of ¹H, ³¹P, and ⁷⁷Se NMR spectroscopy. In chloroform, auranofin undergoes ligand substitution of the tetraacetylthioglucose moiety by a PhS or PhSe group. The reaction is reversible in both cases, but it is characterized by widely different equilibrium constants (ca. 1 for S and at least 10³ for Se). In polar solvents, such as methanol, the reaction is more complex, and the phosphane moiety also undergoes ligand exchange. Some features have been clarified through the investigation of Et₃PAuCl. The elementary processes involved have been characterized by DFT calculations.

The decatungstate anion [W₁₀O₃₂]⁴⁻ is widely used as a photocatalyst in different transformations, during which it undergoes one-electron reduction to [W₁₀O₃₂]⁵⁻, possibly protonated; the bi-reduced species [W₁₀O₃₂]⁶⁻ is obtained by ensuing disproportionation. Relativistic DFT calculations were used to predict the UV-VIS spectra and EPR parameters of all such species.