On the molecular and electronic structure of matrine-type alkaloids

A systematic study of the molecular and electronic structure of the eight possible members in the trans-matrine series and of two dehydro-derivatives, sophocarpine and sophoramine, has been performed. According to density functional theory (DFT) calculations these alkaloids exhibit a variety of form and junction of the four six-membered rings and all but sophocarpine have a strong preference for one conformation. Sophocarpine is predicted to have a marked conformational flexibility at the lactamic nitrogen and to exist as a mixture of two nearly isoenergetic conformers (C/D-trans and -cis) in the gas phase or solution. The theoretical predictions are consistent with the available X-ray experimental results as well as IR and NMR evidence. The absolute configuration of the preferred conformer of each compound has been established theoretically and corroborated with the specific optical rotation calculated at the sodium D line. The conformational equilibrium of sophocarpine has also been supported by this physical property. The computed gas-phase proton affinity of matrines indicates a basicity comparable to that of other polycyclic proton sponges. The lowest-energy electronic transitions have been characterized by time-dependent DFT calculations as mainly due to excitations spanning the frontier orbitals π(NCO), n(O), n(N_aminic), and π^*(CO). The electronic structures have also been studied by measuring and calculating significant features of the NMR and photoelectron spectra. In particular, a representative set of NMR chemical shifts and nuclear spin-spin coupling constants, obtained with DFT formalisms, compares favourably with experiment. Notably, the stereoelectronic hyperconjugative effects on Δδ(H_eq/H_ax) and Δ¹J(CH_eq/CH_ax) of the >N-CO- groups is correctly accounted for by the theoretical results. Based on ab initio outer valence Green's function calculations, a reliable description of the uppermost bands in the photoelectron spectra has been advanced. The splitting and sequence of the ionization energies reflect a complex interaction of the n and π chromophores.