Computational studies sulfonylureas molecules

Abstract

Computational studies are very important for biologically active molecules and for the development of new drugs, because the biological activities depend on their molecular structures and properties. This work presents the results of a conformational study of selected sulfonylureas molecules in vacuo. Sulfonylureas are a class of synthetic organic compounds containing a thiourea group (sulfonyl and urea groups bonded together) attached to a benzene ring, a substituent (R) on the thiourea, and another substituent (R) linked to the benzene ring by a two– or three– carbon atom chain attached to an oxygen atom which is directly attached to the benzene ring in para position with respect to the thiourea group. The interest in this class of compounds is that some compounds are used in the treatment of type 2 diabetes. Molecules with different R and R substituents have been considered. Full-optimization calculations were performed in vacuo using Density Functional Theory (DFT) and Hartree Fock (HF) methods. Attention was given to the identification of stable conformers of each of the molecules considered (obtainable by rotation of relevant bonds) and of the conformers’ stabilizing factors. The molecular properties considered include the relative energies of the conformers, the parameters of the intramolecular hydrogen bonds (IHBs), the dipole moments, the HOMO–LUMO energy gaps, and the vibrational frequencies of relevant bonds (in particular, the N–H bonds, because the N–H groups may be IHB donors). The results indicate that the number and type of IHBs are the major stabilizing factors. A maximum of three simultaneous IHBs are possible in the thiourea group. This includes the presence of bifurcated IHBs (bifurcation on the hydrogen atom of the donor), which are present in most of the stable conformers. The vibrational frequencies of the N–H bonds show changes occurring when these bonds form IHBs. The changes showed a rare phenomenon, that is, a blue shift (frequency increase) for certain IHBs, and also a much more common phenomenon (red shift. i.e., frequency decrease) for other IHBs. The geometry of the thiourea moiety, the nature of R and R, the orientation and the length of the chain between the benzene ring and R also show some influence on the calculated molecular properties.