Unravelling the Nature of Halogen and Chalcogen Intermolecular Interactions by Charge Density Analysis

Abstract

The thesis entitled “Unravelling the Nature of Halogen and Chalcogen Intermolecular Interactions by Charge Density Analysis" consists of five chapters. A basic introductory section describes the topics relevant to the work and the methods and techniques utilized. The main focus of the present work is to characterize the interaction patterns devoid of strong classical hydrogen bonds. The case studies include halogen bonds and hydrogen bonds involving bromine (as a halogen bond donor and hydrogen bond acceptor), intermolecular chalcogen bond formation involving sulphur, type I Br Br contacts, type II F F and F S interactions and S-H S hydrogen bonds. Chapter 1 discusses experimental and theoretical charge density analyses on 2,2-dibromo-2,3-dihydroinden-1-one which has been carried out to quantify the topological features of a short C Br···O halogen bond with nearly linear geometry (2.922Å, C Br···O=172.7) and to assess the strength of the interactions using the topological features of the electron density. The electrostatic potential map indicates the presence of the “- hole” on bromine while the interaction energy is comparable to that of a moderate O-H O hydrogen bond. In addition, the energetic contribution of C-H···Br interaction is demonstrated to be on par with that of the C-Br···O halogen bond in stabilizing the crystal structure. Chapter 2 discusses an organic solid, 4,7-dibromo-5,6-dinitro-2,1,3-benzothiadiazole that has been designed to serve as an illustrative example to quantitatively evaluate the relative merits of halogen and chalcogen bonding in terms of charge density features. The compound displays two polymorphic modifications, one crystall zing in a non-centrosymmetric space group (Z =1) and the other in a centrosymmetric space group with two molecules in the asymmetric unit (=2). Topological analysis based on QTAIM clearly brings out the dominance of chalcogen bond over the halogen bond along with an indication that halogen bonds are more directional compared to chalcogen bonds. The cohesive energies calculated with the absence of both strong and weak hydrogen bonds as well as stacking interaction are indicative of the stabilities associated with the polymorphic forms. Chapter 3 discusses the role of a type I C-Br Br-C contact and what drives the contact i.e. how a dispersive interaction is stabilized by the remaining contacts in the structure. In the process we observe the role the Br2Cl motif which is quite unique in its nature. Also the role of the bromine atoms in stabilizing the stacking interactions has been shown by the electrostatic potentials which are oriented perpendicular to the plane of the benzene ring. Chapter 4 discusses the enigmatic type II C-F F-C and C-FS-C interactions in pentafluorophenyl 2,2- bithiazole. Both the interactions are shown to be realistic “-hole” interactions based on high resolution X-ray charge density analysis. As fluorine is the most electronegative element, its participation in halogen bonding wherein the electrostatic potential around the atom gets redistributed to form regions of electron depletion and accumulation had time and again been speculated but never observed. In this chapter the experimental charge dnsity analysis clearly identifies the “-hole” on fluorine and distinguishes the C-F S-C interaction as a halogen bond rather than the chalcogen bond. Chapter 5 discusses the experimental charge density analysis of the hitherto unexplored S-H S hydrogen bond in crystal structures. The work highlights how relatively small is the number of crystal structures which are constructed by the S-H S hydrogen bond compared to the X-H S hydrogen bond via Cambridge Structural Database (CSD) analysis. The potential S-H S hydrogen bond is studied in three isomeric mercaptobenzoic acids with experimental charge density collected on 2-mercaptobenzoic acid and theoretical estimates made on 3- and 4-mercaptobenzoic acid. The strength and directionality of the S-H S hydrogen bond is demonstrated to be mainly due to the conformation locking potential of intramolecular S O halogen bond.