The thesis entitled "Phase Behaviour in Crystalline Solids: Exploring the Structure Guiding Factors via Polymorphism, Phase Transitions and Charge Density Studies" consists of five chapters divided into two parts. A basic introductory section describes the topics relevant to the work and the methods and techniques utilized. Part A contains two chapters that discuss the structural aspects related to polymorphism, solvatomorphism, conformational preferences and phase transitions exhibited by active pharmaceutical ingredients (APIs). It also discusses the structure-property correlations in API crystal forms and the possible utility of second harmonic generation (SHG) for their bulk characterization. Part B has three chapters that discuss experimental and theoretical charge density analyses of intra-and intermolecular interactions that play structure guiding roles in some of the APIs discussed in Part A. The main focus of the present work is to characterize the interaction patterns devoid of strong classical hydrogen bonds. The case studies include multifurcated C - H …O hydrogen bonds, the “carbon bonding” and chalcogen interactions involving Se and S atoms. In addition to charge density studies, in situcryocrystallography and molecular complexation experiments have been employed to examine structural consequences of chalcogen bonding. Further, Appendices 1 and 2 describe phase transition studies on the inorganic mineral kröhnkite and its high temperature phase transitions leading to novel inorganic structural types. Part A: Polymorphism and phase behaviour in Active Pharmaceutical Ingredients (APIs) Chapter 1 discusses case studies of polymorphism, supramolecular preference sand phase transitions exhibited by active pharmaceutical ingredients (APIs). Section 1.1 deals with the polymorphism of an anti-oxidant drug candidate ebselen and its hydroxyl derivative. The potential of organoselenium compounds to form a Se…O chalcogen bonded supramolecular recognition unit (synthon) has been established in these polymorphs and its generality is substantiated with the help of a Cambridge Structural Database (CSD) analysis. Section 1.2 demonstrates the utility of the ‘chalcogen bonded supramolecularsynthon’ in generating molecular complexes of APIs. A series of salts and co-crystals of the amyotrophic lateral sclerosis drug Riluzole have been synthesized in order to evaluate the structure directing role of S…O chalcogen bonded synthon in their crystal structures. Section 1.3adescribes the generation of polymorphs and solvatomorphs of the antidepressant drug candidate fenobamand associated phase transitions. The tautomeric preference in this molecule has been rationalized from the crystal structure analysis and abinitioenergy calculations. Further, section 1.3b utilizes chemical derivatization as a means to experimentally simulate thetautomeric preference and molecular conformations in several derivatives of fenobam and thiofenobam. Section 1.4 describes the issue of solvatomorphism and the generation of the fifth solvatomorph of gallic acid, its structural complexity and temperature induced phase transitions. The ability of solvent water molecules to drive structural diversity, by forming ‘hydration synthons’,is demonstrated in this case. Chapter 2 presents a novel methodology for the detection of polymorphic impurities in APIs based on second harmonic generation (SHG).The SHG based method has been employed to polymorphic mixtures of fenobam, hydrochlorothiazide, pyrazinamide, tolbutamide, curcumin, febuxostat and nimesulide.The conventional methods such as powder X-ray diffraction (profile fitting analysis), FT-IR, Raman spectroscopy and thermal analysesto detect the presence of polymorphic impuritiesin bulk API samples are employed on the mixtures of these API samples and the impurity detection limits are compared with the proposed SHG methodology. The APIs used in these case studies were screened for their SHG efficiency using quantum chemical calculations of hyperpolarizability and HOMO-LUMO charge redistribution behaviour. Further, a correlation with the crystal symmetry, relative packing arrangement of molecules and the observed SHG efficiency have been discussed in of some of these cases. Part B: Exploring the nature and structural consequences of nonbonding interactions in molecular crystals Chapter 3 discusses the electron density features of quasi-trifurcated CH…Cl/CH…O interaction motifs leading to ‘carbon bonding’ and a trifurcated CH…O hydrogen bond motif. Section 3.1 describes the experimental and theoretical charge density analyses of quasi-trifurcated CH…Cl and CH…O motifsand investigates the existence of “carbon bonding” in solid state. The experimental charge density evidence for “carbon bonding” have been analyzed in cases of fenobam and dimethylamine: 4-hydroxybenzoic acid complex. The existence of this unconventional interaction, which roughly mimics the transition state geometry of SN2 (bimolecular nucleophilic substitution) reaction, is further established by a CSD analysis. Section 3.2 describes the experimental and theoretical charge density analyses of ferulic acid and compares the topological features associated with a trifurcated CH…O hydrogen bond motif, with corresponding strong classical OH…O hydrogen bonds. The study demonstrates the “Gulliver effect” of weak interactions in charge density terms. Charge density based interaction energy calculations via EPMM and EML methods have been utilized in this context to evaluate the relative strength of such interactions. Chapter 4 discusses the charge density features of intermolecular chalcogen bonding interactions involving selenium and sulphur atoms.Section 4.1 describes the experimental and theoretical charge density analyses of ebselen and its hydroxyl derivative. The charge density characterization of the conserved chalcogen bond synthon (discussed in chapter 1, section 1.1) has been carried out and electronic nature and geometric dependence of Se…O interactions have been explored. The mechanism of drug action of ebselen has been correlated with the experimentally observed charge density distribution around the intramolecular SeC and SeN bonds. Section 4.2 explores the homochalcogen interactions such as S…SandSe…Se in phenol analogues. In situ cryocrystallographic studies on thiophenol, selenophenol and their solid solutions are described. Veggard’s law-like behaviour observed in these solid solutions have been rationalized and the S…S and Se…Sehomochalcogen interactions have been evaluated in these liquid systems which are devoid of any other packing forces such as strong hydrogen bonds. Chapter 5 discusses the conformation locking potential of intramolecular S…O chalcogen bonding in sulfadrugs. Section 5.1 discusses conformation locking in the antibioticdrugsulfamethizole. A two pronged approach has been adopted in the study; a) generation of cocrystals and salts of sulfamethizole for the ‘experimental simulation’ of the molecular conformation, b) evaluation of charge density distribution around the intramolecular S…O interaction region in sulfamethizole. Section 5.2 describes the effect of ‘simple hybridized orbital geometry’ in the formation of intramolecular S…O chalcogen bonding. The experimental charge density analysis of the carbonic anhydrase inhibitor drug acetazolamide has been carried out and the two different intramolecular S…O geometries have been compared in terms of the charge density topology. The analysis highlights the advantage of “orbital geometry” consideration over the conventional distance-angle criteria in assessing nonbonded interactions.

The thesis entitled “Organic fluorine in crystal engineering: Consequences on molecular and supramolecular organization” consists of six chapters. The main theme of the thesis is to address the role of substituted fluorine atoms in altering the geometrical and electronic features in organic molecules and its subsequent consequences on crystal packing. The thesis is divided into three parts. Part I deals with compounds that are liquids under ambient conditions, crystal structures of which have been determined by the technique of in situ cryocrystallography. Part II demonstrates the utilization of in situ cryocrystallography to study kinetically trapped metastable crystalline phases that provide information about crystallization pathways. In part III, crystal structures of a series of conformationally flexible molecules are studied to evaluate the consequences of fluorine substitution on the overall molecular conformation. The genesis and stabilization of a particular molecular conformation has been rationalized in terms of variability in intermolecular interactions in the crystalline state. Part I. In situ cryocrystallography: Probing the solid state structures of ambient condition liquids. Chapter 1 discusses the crystal structures of benzoyl chloride and its fluorinated analogs. These compounds have been analysed for the propensity of adoption of Cl···O halogen bonded dimers and catemers. The influence of conformational and electronic effects of sequential fluorination on the periphery of the phenyl ring has been quantified in terms of the most positive electrostatic potential, VS,max (corresponding to σ-hole) on the Cl-atom. It is shown that fluorine also exhibits “amphoteric” nature like other heavier halogens, particularly in presence of electron withdrawing groups. Although almost all the derivatives pack through C–H···O, C–H···F, C–H···Cl, Cl···F, C–H···π and π···π interactions, the compound 2,3,5,6-tetrafluorobenzoyl chloride exhibited a not so commonly observed Cl···O halogen bonded catemer. On the other hand, the proposed Cl···O mediated dimer is not observed in any of the structures due to geometrical constraints in the crystal lattice. Chapter 2 presents the preferences of fluorine to form hydrogen bond (C–H···F) and halogen bonds (X···F; X= Cl, Br, I). Crystal structures of all three isomers of chloro-, bromo-and iodo-fluorobenzene have been probed in order to gain insights into packing interactions preferred by fluorine and other heavier halogens. It has been observed that homo halogen…halogen (Cl···Cl, Br···Br and I···I) contacts prevail in most of the structures with fluorine being associated with the hydrogen atom forming C–H···F hydrogen bond. The competition between homo and hetero halogen bonds (I···I vs I···F) is evident from the packing polymorphism exhibited by 4-iodo fluorobenzene observed under different cooling protocols. The crystal structures of pentafluoro halo (Cl, Br, I) benzenes were also determined in order to explore the propensity of formation of homo halogen bonds over hetero halogen bonds. Different dimeric and catemeric motifs based on X···F and F···F interactions were observed in these structures. Chapter 3 focuses on the effect of different cooling protocols in generating newer polymorphs of a given liquid. The third polymorph (C2/c, Z'=6) of phenylacetylene was obtained by sudden quenching of the liquid filled in capillary from a hot water bath (363 K) to the nitrogen bath (< 77 K). Also, different polymorphs were obtained for both 2¬fluoro phenylacetylene (Pna21, Z'=1) and 3-fluoro phenylacetylene (P21/c, Z'=3) when crystallized by sudden quenching in contrast to the generally followed method of slow cooling which results in isostructural forms (P21, Z'=1). The rationale for these kinetically stable “arrested” crystalline configurations is provided in part II of the thesis. Part II. Tracing crystallization pathways via kinetically captured metastable forms. Chapter 4 explains the utilization of the new approach of sudden quenching of liquids (detailed in chapter 3) to obtain kinetically stable (metastable) crystalline phases that appear to be closer to the unstructured liquids. Six different examples namely, phenylacetylene, 2-fluorophenylacetylene, 3-fluorophenylacetylene, 4-fluorobenzoyl chloride, 3-chloro fluorobenzene and ethyl chloroformate are discussed in this context. In each case, different polymorphs were obtained when the liquid was cooled slowly (100 K/h) and when quenched sharply in liquid nitrogen. The relationship between these metastable forms and the stable forms (obtained by slow cooling) combined with the mechanistic details of growth of stable forms from metastable forms provides clues about the crystallization pathways. Part III. Conformational analysis in the solid state: Counterbalance of intermolecular interactions with molecular and crystallographic symmetries. Chapter 5 describes the crystal structures of a series of conformationally flexible molecules namely, acetylene and diacetylene spaced aryl biscarbonates and biscarbamates. While most of the molecules adopt commonly anticipated anti (transoid) conformation, some adopt unusual cisoid and gauche conformations. It is shown that the unusually twisted conformation of one of the compounds [but-2-yne-bis(2,3,4,5,6¬pentafluorocarbonate)] is stabilized mainly by the extraordinarily short C–H···F intermolecular hydrogen bond. The strength of this rather short C–H···F hydrogen bond has been authenticated by combined single crystal neutron diffraction and X-ray charge density analysis. It has also been shown that the equi-volume relationship of H-and F-atoms (H/F isosterism) can be explored to access various possible conformers of a diacetylene spaced aryl biscarbonate. While biscarbonates show variety of molecular conformations due to absence of robust intermolecular interactions, all the biscarbamates adopt anti conformation where the molecules are linked with antiparallel chains formed with N–H···O=C hydrogen bonds. Chapter 6 presents a unique example where the commonly encountered crystallographic terms namely, high Z' structure, polymorphism, phase transformation, disorder, isosterism and isostructuralism are witnessed in a single molecular species (parent compound benzoylcarvacryl thiourea and its fluorine substituted analogs). The origin of all these phenomenon has been attributed to the propensity of formation of a planar molecular dimeric chain mediated via N–H···O [R2 (12)] and N–H···S [R2 (8)] dimers.

<p></p><p>Global demand for high performance, low cost, and eco-friendly electronics is ever increasing. Ion/charge transport ability and mechanical adaptability constitute two critical performance metrics of battery and semiconductor materials, which are fundamentally correlated with their structural dynamics under various operating conditions. It is imperative to reach the mechanistic understanding of the structure-property relationships of electronic materials to develop principles of materials design. Nevertheless, the intricate atomic structure and elusive phase behaviors in the operation of devices challenge direct experimental observations. Herein, we employ a spectrum of modeling methods, including quantum chemistry, ab-initio modeling, and molecular dynamics simulation, to systematically study the phase dynamics and physico-mechanical behaviors of multiple electronic materials, ranging from transition-metal cathodes, polymer derived ceramics anodes, to organic semiconductor crystals. The multiscale atomistic modeling enriches the fundamental understanding of the electro-chemo-mechanical behaviors of battery materials, which provides insight on designing state-of-the-art energy materials with high capacity and high structural stability. By leveraging the genetic-algorithm refined molecular modeling and phase transformation theory, we unveil the molecular mechanisms of thermo-, super- and ferroelastic transition in organic semiconductor crystals, thus promoting new avenues of adaptive organic electronics by molecular design. Furthermore, the proposed computational methodologies and theoretical frameworks throughout the thesis can find use in exploring the phase dynamics in a variety of environmentally responsive electronics.</p><p></p>

We have presented a thorough experimental investigation of electroabsorption spectroscopy on quasi-one-dimensional organic molecular crystals such as PTCDA and MePTCDI vapor deposited thin films to clarify the involvement of the charge-transfer exciton in the lowest excited state. By a self-built experimental setup, two kinds of electroabsorption measurements, called &amp;quot;perpendicular&amp;quot; and &amp;quot;parallel&amp;quot; measurements, were conducted at room temperature in ambient air. The crystalline texture of PTCDA and MePTCDI thin film samples are characterized by X-ray diffraction measurements. Current-voltage, capacitance-frequency and capacitance-voltage measurements are performed to clarify the electric field distribution inside organic layers. The results from electrical measurements show that only under certain conditions (electroabsorption measurements with proDC bias), the perpendicular and parallel electroabsorption meaurements can be directly compared. The electroabsorption spectra of MePTCDI and PTCDA thin films can be interpreted by neither pure Frenkel exciton nor pure charge-transfer exciton model. Essential features of electroabsorption spectra of MePTCDI and PTCDA thin films can be understood by the the mixture of Frenkel and charge-transfer exciton model. However, there is still a discrepancy in the directional properties of electroabsorption signals between experimental results and modle calculations. This small discrepancy suggests that a full interpretation of electroabsorption spectra of quasi-one-dimensional organic molecular crystals needs further experimental and theoretical investigations.