DFT Study of the Structural, Electronic, Bonding Nature, NBO Analysis, and Thermodynamic Properties of Halogenated (F, Cl, Br) and Heteroatom (O, N, S) doped Cyclopropane

Abstract

Background: The chemistry of cyclopropanes has been widely studied over the years as a result of its high reactivity which is due to its highly strained ring. The cyclopropane ring is highly significant in drug research as the 10th most frequently found ring in small molecules and as such, there is a need for research to improve further the reactivity of cyclopropanes in natural products and pharmaceuticals. In this work, we present an extremely comprehensive and detailed investigation on a variety of properties of cyclopropane including Geometrical properties, bonding nature, bond polarity index (BPI), natural bond orbitals (NBO), orbital charge analysis, Density of states (DOS), molecular electrostatic potential (MEP), UV-spectral analysis, electron ionization, affinity and accompanied process, local reactivity parameters and the effects of substitution of heteroatoms Nitrogen (N-doped C3H8), Oxygen (S-doped C3H8) and Sulphur (S-doped C3H8) each in the place of carbon atom (otherwise known as doping) and also the substitution effects of Fluorine, Chlorine and Bromine each on one hydrogen atom in cyclopropane molecule (halogenation) and investigate how it chemically affects the properties outlined above. Results: It is observed from conceptual (CDFT) results that S-doped C3S has the highest reactivity of all the molecules studied. The UV-spectral analysis also predicts doped C3S as the molecule that gives the highest Bathochromic shift of all the molecules. Some other properties studied also give us the most potential sites for electrophilic and nucleophilic attack by electrophiles and nucleophiles. The NBO investigation revealed the strongest stabilization to the cyclopropane molecule for the heteroatoms follow the trend C3S<C3N<C3O. It is also observed that for the halogens the strongest stabilization for the cyclopropane molecule follows the trend C3Br<C3Cl<C3F<C3. The strong intra-molecular hyperconjugation interaction of the 2-centered bond (BD) and CR electrons of C-C anti C-C bond in the ring leads to stabilization of the cyclopropane ring as evident from the order perturbation energy analysis. Conclusion: The results obtained from the research will help scientists further improve on the reactivity of cyclopropanes as a motif in drug discovery through substitution (halogenation) and doping with heteroatoms (O, S, N)