Biguanide-dihydropyrimidine dual scaffolds with impressive basicities according to DFT calculations

Abstract

Gas phase basicities (GBs) and proton affinities (PAs) of a new class of uncharged organo-superbases based on biguanide-dihydropyrimidine dual scaffolds with several electron donating groups, were computationally assessed by DFT- B3LYP/6-311+G(d,p) calculations. Two remarkable strategies for superbase designing based on intramolecular hydrogen bonds (IHBs) and aromatization of the unsaturated rings were implemented to obtain structures with high basicity properties. The employed protocol leads to the design of novel super/hyperbases with significant basicity range of 1089.45–1262.69 kJ mol−1. To examine aromaticity changes in the unsaturated rings upon protonation, Harmonic Oscillator Model of Aromaticity (HOMA), Harmonic oscillator model of electron delocalization (HOMED) parameters and the nucleus-independent chemical shift (NICS) were utilized. Electrostatic potential maps for all designed structures were further applied for electron density distribution evaluation. Furthermore, Natural Bond Orbital (NBO) method was used to study the nature of the formed IHBs in the structures 1–11.