Crystal Engineering Approach to Achieve Soft Organic Solids: Structure-Mechanical Property Correlation Studies

Rao, G. Rama Krishna (2014) Crystal Engineering Approach to Achieve Soft Organic Solids: Structure-Mechanical Property Correlation Studies. PhD thesis, Indian Institute of Science Education and Research Kolkata.

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The work presented in this thesis is an attempt of designing the soft organic solid structures based on crystal engineering principle and to establishing reliable structure-property relationships by considering mechanical response. Chapter 1 gives an overview of the streams in the development of (a) crystal engineering from solid state organic chemistry which includes solid state pharmaceutical chemistry, pharmaceutical co-crystals, polymorphism, mechanical behaviour of molecular crystals (b) structure-property correlation in molecular crystals (c) implications for tabletability (d) crystal engineering principles to mechanochromic luminescence materials (e) importance of mechanochemistry (f) importance of nanoindentation technique and (g) importance of designing the soft organic materials. Chapter 1 also deals with the importance of mechanical properties in materials science and crystal engineering and a glossary of terms used in this Thesis. Different forms (green and cyan) of AVB·BF2 exhibit different levels of reversible ML behaviour due to their distinct mechanical behavior as well as anisotropy in internal packing. Brittle (Green) form does not show prominent ML property due to the absence of slip planes, whereas bending/soft form shows a very prominent ML property at room temperature due to the presence of slip planes, which is described in Chapter 2. In Chapter 3, co-crystallization method has been employed based on crystal engineering approach to prepare soft crystalline forms (shearing and bending type cocrystals) of cda from using brittle vanillin co-formers/sbovan to further study structuretabletability correlation. The relationship among crystal structure, mechanical property and tensile strength of tablets is successfully explained in vanillin isomers and their respective co-crystals. The comparison of tensile strengths measured for the resulting tablets allowed ranking tablets in following order: sbovan:cda > evan > van > ivan:cda > evan:cda > van:cda > sbovan > ivan. This clearly suggests that bending crystals are good for making good quality tablets. The results not only have implications for tabletability of APIs, but also provide structure based understanding for the design of soft organic materials. Co-crystals are generally prepared by traditional methods, mostly from solutions. In previous studies, mechanochemical reactions were exploited to control the covalent and supramolecular reactions, separately. Here, both the covalent and supramolecular reactions (polymorph control) are combined in a single-pot mechanochemical and supramolecular reaction to directly obtain the (i) desired polymorphs (ii) co-crystals (three component reaction). The starting compounds bearing weakly interacting groups such as -F, -Cl, -Br, -I, -CH3, -OCH3 were selected to achieve soft or plastically deformable crystals. Based on the crystal engineering principles these groups are employed to introduce slip planes in the crystal structure, which are discussed in the Chapter 4. So far, the organic soft materials have been prepared on the basis of trial and error, which requires a lot of research effort. A reliable structure-property correlation is necessary to design soft organic materials. For this, crystal engineering approach is employed to introduce slip planes into the crystal packing by keeping the weakly interacting functional groups ( like –F, -Cl, -Br, -I, -CH3 and -OCH3) as substituents in the target compounds, which is discussed in the Chapter 5. Chapter 6 deals with synthesis, crystal structure analysis, relative thermal stability studies of ten salts of olanzapine (OLP), and solubility studies on OLP:BBA drug-drug salt.

Item Type: Thesis (PhD)
Additional Information: Supervisor: Dr. C. Malla Reddy
Uncontrolled Keywords: Correlation Studies; Crystal Engineering; Mechanochromic Materials; Soft Organic Solids; Structure; Mechanical Property; Nanoindentation; Supramolecular Chemistry
Subjects: Q Science > QD Chemistry
Divisions: Faculty of Engineering, Science and Mathematics > School of Chemistry
Depositing User: IISER Kolkata Librarian
Date Deposited: 20 Nov 2014 11:12
Last Modified: 20 Nov 2014 11:13

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