Theoretical Investigations On Weak Intermolecular Interactions In The Crystals Of Fenamic Acid,Nicotinic Acid And Their Derivatives

Crystal engineering,as an important field of modern chemistry research,is an advantageous approach from molecular to material realization.Currently,it is a wide range of applications in the field such as drug design and functional materials.The weak interactions,for instance,hydrogen bonds,halogen bonds,van der Waals forces and ?···? interactions in the crystal play a great role in the structure,symmetry and stability of the crystals.Therefore,in-depth exploration of the weak intermolecular interactions in crystal structures is of great significance for the development of crystal engineering.In the thesis,theoretical calculations are carried out by using Gaussian09 and CrystalExplorer software,based on M06-2X method in density functional theory(DFT),QTAIM in molecular and Hirshfeld surface analysis,and the weak interactions between fenamic acid and nicotinic acid are explored and discussed.This thesis is divided into four parts:Chapter One: Introduction.In this chapter,the author gives a brief introduction of the significance of supramolecular chemistry and crystal engineering for the development of chemical research as well as its important influence on the types of weak interactions existing in crystal molecules.It includes the research background,the types of weak interactions among crystals,the research progress of crystal engineering,and the content and purpose of the researsh in this chapter.Chapter Two: Theoretical Calculation Methods.This chapter mainly contains the development of quantum chemistry,the quantum chemical calculation method of weak interaction between molecules and the Hirshfeld surface analysis to study the weak interaction between molecules and so on.Chapter Three: The Origin of Two Asymmetric Units in Fenanic Acid Crystals.In this chapter,firstly,we investigated the torsion angle,bond length,conformation energy and other properties of different conformations A,B,P,L of the molecules of fenamic acid crystal.Thecomplexes with different conformations were studied in detail and analyzed by QTAIM.We used the M06-2X density functional approach to optimize geometry of the single fenamic acid molecule and the predicted fenamic acid molecule with no geometric constraints and partially optimize the two conformational isomerism of the fenamic acid crystal.It shows that there are the differences between the torsion angles and the bond lengths of the four conformers,indicating different stacking modes and weak intermolecular forces in their respective crystals.Then,we also explored their complexes and found that there are three other types of hydrogen bonds that can be removed from the pair: one is the reaction with the carboxyl groups of conformations A,B,P conformations(ie,O-H and C O bonds)adjacent molecules,which is a significant impact on the strength of hydrogen bonds,the other two are intermolecular substituent interactions and the interaction between unsubstituted benzene rings.It is well known that the hydrogen bond interaction plays a decisive role in the direction of crystal growth and also contributes to the stability of the crystal.Therefore,we compared the bond length of these three hydrogen bonds and the intermolecular interactions.Conformers A and B of fenamic acid can also be bonded to each other by the asymmetric hydrogen bond O-H···O to form Z'= 2 fenamic acid crystals because their conformational energy is almost equal to the hydrogen bond strength of O-H···O,which is why they can co-exist.Finally,we compare complexes containing conformers A,B and P of the same conformations with the intermolecular forces of these complexes analyzed by QTAIM.The entire working study found that asymmetric O-H···O hydrogen bonds in the fenamic acid crystals with Z'= 2 are even stronger than symmetrical O-H···O hydrogen bonds in crystals with Z' = 1.At the same time,the alternating arrangement of the molecular pairs of the conformers A and B in the fenamic acid crystal of Z'= 2 is the same as that of the conformers P in the strength of fenamic acid crystal with Z' = 1.In alternate conformers A and B,the interaction between adjacent two adjacent isomers and the unsubstituted benzene ring also plays a significant role in the stability of the conformer.Therefore,fenamic acid crystals with Z'= 2 are the preferred arrangements.This result can be a valuable research for the origin of Z '= 2 structure or higher Z' structure.Chapter Four: Hirshfeld surface analyzed weak interaction forces in crystal molecules.In this chapter,we performed Hirshfeld surface analysis of the crystal structures obtained from the experiments with fenamic acid and its derivatives and nicotinic acid and its derivatives.The crystal structure of fenamic acid and its derivatives and nicotinic acid and its derivatives has been obtained from the Crystal Open Database.It can be seen from the crystal structure that the same kind of molecule may form different crystal structures.Therefore,we investigated the weak interactions in the crystal molecules by using CrystalExplorer software for the experimental crystal structure.In this work,we have done a corresponding Hirshfeld surface analysis for eachcrystal structure,showing the intermolecular interaction according to the intermolecular interaction distance.In addition,fingerprinting analysis is used to determine the weak interactions between hydrogen bonds,halogen bonds and ?-? existing in the molecule.We also conducted a comparative analysis of the different crystals formed by the same type of molecules and discussed the differences in the weak interaction between the two molecules as a result of their molecular conformations and arrangement.