Density Functional Theory Based Studies of Reactivity Descriptors to Predict the Regioselectivity of Chemical and Biological Systems

Abstract

This thesis describes a novel study on Conceptual Density Functional Theory (DFT) newlinebased reactivity descriptors for use in predicting the regioselectivity of large systems, newlinebimolecular systems. The challenges of bio-systems in particular the large number of atoms newlineand high structural flexibility, made the way to a routine application of DFT more laborious. newlineTo cope with extended systems, a fragmentation based approach has been developed (given newlinethe name One-into-Many model) which is seen to lead to a reliable determination of the newlineregioselectivity of model biomolecular systems. newlineIn the first part of the thesis, a brief review of literature, objectives and motivation for newlinethe present thesis are given. An overview of the Conceptual DFT is given, which provides the newlinetheoretical foundation of different reactivity descriptors. These descriptors enable us to newlineunderstand experimental observations in an elegant way. An important aim of this thesis is to newlineverify and interpret the correlation of these descriptors with the experimental studies at newlinemacromolecular level. Some advances achieved in last few years to predict the newlineregioselectivity of the large bio-molecular systems using Conceptual DFT based reactivity newlinedescriptors are discussed in detail. newlineSo far there has been no schematic study for modeling or analysing the regiochemistry newlineof large biomolecular systems using DFT-based reactivity descriptors. The second newlinepart of the thesis discusses the development of a new model (named as One-into-Many ) to newlinepredict the regioselectivity of large chemical and biological systems. Large chemical and newlinebiological systems with multiple reactive sites are proposed to be broken into small fragments newlinehaving at least one reactive site in each fragment. The environment around each reactive site newlineis mimicked by incorporating a buffer zone. Local reactivity is evaluated for each reactive newlinesite adopting a new modified approach of local hardness, and#951;(r ) . Theoretical justification in newlinefavour of using the local hardness based descriptor to compare the intermole