Meta-Hybrid Density Functional Theory Prediction of the Reactivity, Stability, and IGM of Azepane, Oxepane, Thiepane, and Halogenated Cycloheptane

Tomsmith O Unimuke; Hitler Louis; Ededet A Eno; Ernest C Agwamba; Adedapo S Adeyinka

doi:10.1021/acsomega.1c07361

Meta-Hybrid Density Functional Theory Prediction of the Reactivity, Stability, and IGM of Azepane, Oxepane, Thiepane, and Halogenated Cycloheptane

ACS Omega. 2022 Apr 15;7(16):13704-13720. doi: 10.1021/acsomega.1c07361. eCollection 2022 Apr 26.

Authors

Tomsmith O Unimuke^{1

2}, Hitler Louis^{1

2}, Ededet A Eno^{1

2}, Ernest C Agwamba^{1

3}, Adedapo S Adeyinka⁴

Affiliations

¹ Computational and Bio-Simulation Research Group, University of Calabar, Calabar 540004, Nigeria.
² Department of Pure and Applied Chemistry, Faculty of Physical Sciences, University of Calabar, Calabar 540004, Nigeria.
³ Department of Chemical Sciences, Clifford University Owerrinta, Abia State 440001, Nigeria.
⁴ Research Centre for Synthesis and Catalysis, Department of Chemical Sciences, University of Johannesburg, Johannesburg 2006, South Africa.

Abstract

The application of plain cycloalkanes and heterocyclic derivatives in the synthesis of valuable natural products and pharmacologically active intermediates has increased tremendously in recent times with much attention being paid to the lower cycloalkane members. The structural and molecular properties of higher seven-membered and nonaromatic heterocyclic derivatives are less known despite their stable nature and vast application; thus, an insight into their structural and electronic properties is still needed. Appropriate quantum chemical calculations utilizing the ab initio (MP2) method, meta-hybrid (M06-2X) functional, and long-range-separated functionals (ωB97XD) have been utilized in this work to investigate the structural reactivity, stability, and behavior of substituents on cycloheptane (CHP) and its derivatives: azepane, oxepane, thiepane, fluorocycloheptane (FCHP), bromocycloheptane (BrCHP), and chlorocycloheptane (ClCHP). Molecular global reactivity descriptors such as Fukui function, frontier molecular orbitals (FMOs), and molecular electrostatic potential were computed and compared with lower members. The results of two population methods CHELPG and Atomic Dipole Corrected Hirshfeld Charges (ADCH) were equally compared to scrutinize the charge distribution in the molecules. The susceptibility of intramolecular interactions between the substituents and cycloalkane ring is revealed by natural bond orbital analysis and intramolecular weak interactions by the independent gradient model (IGM). Other properties such as atomic density of states, intrinsic bond strength index (IBSI), and dipole moments are considered. It is acclaimed that the strain effect is a major determinant effect in the energy balance of cyclic molecules; thus, the ring strain energies and validation of spectroscopic specificities with reference to the X-ray crystallographic data are also considered.