Practical Machine Learning Strategies. I. Correcting the MMFF Molecular Mechanics Model to More Accurately Provide Conformational Energy Differences in Flexible Organic Molecules.

A correction to the MMFF molecular mechanics model, based on a neural network trained to reproduce conformer energy differences obtained from ωB97X-V/6-311+G(2df,2p)[6-311G*]//MMFF calculations is described. It is supported for molecules containing H, C, N, O, F, S, Cl, and Br. The correction adds only slightly to the cost of MMFF, and the resulting corrected model is several orders of magnitude faster than ωB97X-V/6-311+G(2df,2p)[6-311G*].

Software for the frontiers of quantum chemistry: An overview of developments in the Q-Chem 5 package.

This article summarizes technical advances contained in the fifth major release of the Q-Chem quantum chemistry program package, covering developments since 2015. A comprehensive library of exchange-correlation functionals, along with a suite of correlated many-body methods, continues to be a hallmark of the Q-Chem software. The many-body methods include novel variants of both coupled-cluster and configuration-interaction approaches along with methods based on the algebraic diagrammatic construction and variational reduced density-matrix methods.

Efficient Protocol for Accurately Calculating C Chemical Shifts of Conformationally Flexible Natural Products: Scope, Assessment, and Limitations.

An efficient protocol for calculating C NMR chemical shifts for natural products with multiple degrees of conformational freedom is described. This involves a multistep procedure starting from molecular mechanics and ending with a large basis set density functional model to obtain accurate Boltzmann conformer weights, followed by empirically corrected density functional NMR calculations for the individual conformers. The accuracy of the protocol (average rms <4 ppm) was determined by application to ∼925 diverse natural products, the structures of which have been confirmed either by X-ray crystallography or independent synthesis.

Revision of the Structure of Acremine P from a Marine-Derived Strain of Acremonium persicinum.

The previously published structure of the fungal metabolite acremine P is revised by re-evaluation of chemical shift values and NOESY data, and by DFT calculations.

Computation-Assisted Structural Elucidation of Epoxyroussoeone and Epoxyroussoedione Isolated from Roussoella japanensis KT1651.

The structures of epoxyroussoenone (1) and epoxyroussoedione (3) isolated from a culture broth of Roussoella japanensis KT1651 were determined. Although NMR spectra provided insufficient structural information, computation of the theoretical chemical shifts with DFT EDF2/6-31G* enabled us to elucidate not only the planar structure, but also the relative configuration. Their ECD (electric circular dichroism) spectra suggested the absolute configurations, which were confirmed with time-dependent DFT calculations employing BHandHLYP/TZVP.

Dehydrative cyclocondensation mechanisms of hydrogen thioperoxide and of alkanesulfenic acids.

Structural features of hydrogen thioperoxide (oxadisulfane, H-S-O-H) and of alkanesulfenic acids (R-S-O-H; R = CH3, CH2CH3, CH2CH2CH3, CH(CH3)2, C(CH3)3, CF3, CCl3) and the mechanisms of their dehydrative cyclocondensation to the respective sulfinothioic acid (H-(S═O)-S-H) and alkyl alkanethiosulfinates (R-(S═O)-S-R) have been studied using coupled cluster theory with single and double and perturbative triple excitations [CCSD(T)] and quadratic configuration interaction with single and double and perturbative triple excitations [QCISD(T)] with the cc-pVDZ basis set and also using second-order Møller-Plesset perturbation theory (MP2) and the hybrid density functionals B3LYP, B3PW91, and PBE1PBE with the 6-311+G(d,p) basis set. The concerted cyclodehydration mechanisms include cyclic five-center transition states with relatively long distance sulfur-sulfur bonding interactions. Attractive and repulsive nonbonding interactions are predicted in the sulfenic acids, transition states, and thiosulfinates.

Structure and biosynthesis of norneolambertellin produced by Lambertella sp. 1346.

Norneolambertellin (1) was isolated from a mycoparasite Lambertella sp. 1346. Combined analysis of the NMR spectra and chemical shift prediction based on molecular orbital calculation successfully revealed a novel pyrano[3,2-c]chromene-2,5-dione structure, which was further confirmed by X-ray crystallographic analysis.

The total synthesis of roquefortine C and a rationale for the thermodynamic stability of isoroquefortine C over roquefortine C.

The first total synthesis of roquefortine C is achieved by implementation of a novel elimination strategy to construct the thermodynamically unstable E-dehydrohistidine moiety. Molecular modeling studies are presented which explain the instability of the roquefortine C structure compared to that of isoroquefortine C.