Halogen Interactions in Halogenated Oxindoles: Crystallographic and Computational Investigations of Intermolecular Interactions.

Megan E. Moberg,Rodrigo A. Lemos Silva,Ted M. Pappenfus,Daron E. Janzen,Demetrio A. da Silva Filho

doi:10.3390/molecules26185487

Abstract

X-ray structural determinations and computational studies were used to investigate halogen interactions in two halogenated oxindoles. Comparative analyses of the interaction energy and the interaction properties were carried out for Br···Br, C-H···Br, C-H···O and N-H···O interactions. Employing Møller–Plesset second-order perturbation theory (MP2) and density functional theory (DFT), the basis set superposition error (BSSE) corrected interaction energy (Eint(BSSE)) was determined using a supramolecular approach. The Eint(BSSE) results were compared with interaction energies obtained by Quantum Theory of Atoms in Molecules (QTAIM)-based methods. Reduced Density Gradient (RDG), QTAIM and Natural bond orbital (NBO) calculations provided insight into possible pathways for the intermolecular interactions examined. Comparative analysis employing the electron density at the bond critical points (BCP) and molecular electrostatic potential (MEP) showed that the interaction energies and the relative orientations of the monomers in the dimers may in part be understood in light of charge redistribution in these two compounds.

Highlights

Molecular crystal engineering relies on various types of intermolecular interactions competing to drive solid-state packing
In order to understand the nature of the orbitals involved in the intermolecular interactions in 1 and 2, natural bond orbital (NBO) calculations were performed at the MP2/def2-TZVP and ωB97X-D/def2-TZVP theory levels
As some complexes present more than one interaction and, sometimes with different types, the attainment of the Quantum Theory of Atoms in Molecules (QTAIM)-based contact energies was conducted by the sum of the different atom pair energies in a complex

Summary

Introduction

Molecular crystal engineering relies on various types of intermolecular interactions competing to drive solid-state packing. A study by Bolotin et al [20] revealed that even weak type I halogen···halogen interactions, involving Br···Br contacts, could be the driving forces for the crystallization of a primary organic peroxo compound. Bauzá et al [23] investigated the importance of substituent effects in a series of multivalent halogen bonding complexes. Among their finds, it can be highlighted that complexes involving electron-withdrawing substituents obtained more favorable binding energy. This study explores the intermolecular features of two halogenated oxindoles by analysis of X-ray crystallographic data and through detailed computational investigations. The halogenated oxindoles of this study possess an ensemble of potential competing intermolecular interactions including hydrogen-bonding and several types of halogen interactions. Molecular electrostatic potential (MEP) maps were examined to help rationalize features of the intermolecular interactions analyzed

Results and Discussion

QTAIM Analysis of Supramolecular Dimers of 1 and 2

Natural Bond Orbital Analysis of Supramolecular Dimers of 1 and 2

Computational Studies

Conclusions