Design and Synthesis of Diaryl (Nitrogenous Heterocycles) Alkanes for their Structural and Biological Studies

Abstract

Interactions can be broadly classified as covalent and noncovalent. Noncovalent interactions are those interactions which does not involve sharing of electrons. Noncovalent interactions form a very wide domain of weak interactions such as ion–ion, ion–dipole, dipole–dipole, classical and non-classical hydrogen bonds, arene–arene (π–π interaction), CH…π interaction, O…arene interaction, S…arene interaction, van der Waals interactions, hydrophobic interactions etc. Molecular organization and molecular interactions are based on noncovalent interactions. Noncovalent interactions are critical in maintaining the three-dimensional structure of large molecules, such as proteins and nucleic acids and are involved in many biological processes. Though noncovalent interactions are weak by nature, combined strength of several noncovalent interactions is sufficient to have a significant effect. Among noncovalent interactions, arene–arene interactions play vital role in stabilizing DNA/RNA structures, protein folding, protein–protein interaction, drug–receptor interaction, asymmetric synthesis, molecular tweezers, supramolecular assemblies etc. Despite their importance, the nature of arene–arene interactions is not well understood because of their weakness and complex nature of mechanism. There are a large number of noncovalent interactions in biological recognition systems; therefore, it is very difficult to find out the contribution of an individual arene–arene interaction from the myriad of other noncovalent interactions. To overcome this difficulty, a number of small molecule model systems have been developed for studying arene–arene interactions in simpler and more controlled environments. One of the strategies adopted for making models is to link two arene moieties with trimethylene linker as it provides suitable distance (3.4 Å) required for the arene–arene interaction. In order to study stacking interactions of nucleic acid bases Browne et al. (1968) synthesized nucleotide analogues in which the bases were connected by a trimethylene linker. The research group at CDRI, Lucknow, following Browne et al. strategy has been engaged since 1995 for studying the arene–arene interactions in pyrazolo[3,4-d]pyrimidine (PP) core (which is isomeric with the biologically important purine) based symmetric and dissymmetric trimethylene compounds. These studies have shown that PP core has strong arene–arene interaction propensity. In addition, proper positioning of the linker and substituent are also important for intramolecular π–π stacking interactions Present work involves the study of effect of increasing and decreasing the number of ring nitrogen in Pyrazolo[3,4-d]pyrimidine (PP) nucleus on intramolecular and intermolecular π–π interactions. Also investigation of role of arene interactions in controlling the conformation of 1,2 diaryl ethanes has been done. Finally, the interplay of weak hydrogen bonding such as CH… N, C-H…O etc. and arene interactions in controlling the conformation of the molecule has been studied. The thesis consists of four chapters which are summarized below. The first chapter of the present work deals with the synthesis of Triazolo[4,5-d]pyrimidine (TP) core based flexible symmetric polymethylene linker compounds for studying the effect of increasing the number of ring nitrogen in PP core on intramolecular and intermolecular π–π interactions. The second chapter of the present work deals with the synthesis of Pyrrolo[2,3-d]pyrimidine (PyP) core based flexible symmetric polymethylene linker compounds for studying the effect of decreasing the number of ring nitrogen in PP core on intramolecular and intermolecular π–π interactions. The third chapter of the present work deals with the synthesis of PP core based dissymmetrical ethylene linker compounds having Phthalazinone/Quinazolinone/ Benzotriazinone on the other end for studying the role of arene interactions in controlling the conformation of 1,2 diaryl ethanes. The fourth chapter of the present work deals with the synthesis of PP core based dissymmetrical polymethylene and butylidine linker compounds having Phthalazinone/Quinazolinone/ Benzotriazinone on the other end for studying the conformation directing role of arene interactions in such molecules.