Ankita A. Doshi

Study of Liquid Crystalline State and Evaluation of its Properties Through a Novel Homologous Series

A novel homologous series α-4-[4′-n-alkoxy benzoyloxy] benzoyl-β-3″,4″-dimethoxy phenyl ethylenes has been synthesized and studied for liquid crystal (LC) properties to understand and establish the relation between molecular structure and liquid crystalline behavior. Twelve members of series were synthesized. All the members except first member of the series are mesomorphic. The hexyloxy to tetradecyloxy homologoues are smectogenic and nematogenic in character. The ethoxy to pentyloxy and the hexadecyloxy homologues exhibit only nematogenic character with the absence of smectogenic mesophase formation. An odd–even effect is observed for the smectic-nematic and the nematic-isotropic transition curves in the phase diagram. The smectic mesophase showed as either the SmA or SmC. The nematic mesophase shows a threaded or Schlieren type texture. Spectral and analytical data confirms the molecular structures of the homologues. The thermal stabilities for the smectic and the nematic are 115.6°C and 156.6°C. The smectogenic and nematogenic mesophase length vary from 7°C to 28°C and from 7°C to 52°C respectively. The transition temperatures were observed through an optical polarizing microscope equipped with heating stage. Thus, the presently investigated novel homologous series is predominantly nematogenic and partly smectogenic with a middle ordered melting type and a considerable mesophase length. The LC properties of the novel series are compared with structurally similar homologous series.

Synthesis and Evaluation of a Novel Liquid Crystalline Homologous Series: α-4-[4′-n-Alkoxy Cinnamoyloxy] Benzoyl-β-3″,4″-Dimethoxy Phenyl Ethylenes

The synthesis and evaluation of a novel series of 12 homologues is presented. Enantiotropic nematogenic mesomorphism is exhibited from the pentyl to hexadecyl homologues. The other homologues are not liquid crystalline. Smectic mesomorphism is absent in all homologues. Transition temperatures were determined using an optical polarizing microscope equipped with a heating stage. The transition curves of a phase diagram behave in a normal manner. An odd–even effect is observed for the N-I transition curve. The textures of the nematic phase are of the threaded or Schlieren type. Mesomorphic–isotropic transition temperatures range from 152°C to 178°C. The nematogenic phase length varies between 24°C and 51°C. The nematic thermal stability is 163.1°C. Thus, the novel homologous series is entirely nematogenic without the exhibition of smectogenic character, and is of a middle ordered melting type. Analytical and spectral data support the molecular structures. Liquid crystal (LC) properties of the novel series are compared with structurally similar homologous series.

Dependence of Molecular Structure on Mesomorphic Behavior with Special Reference to Central Bridge

A novel homologous series of liquid crystalline 4-(4′-n-alkoxy cinnamoyloxy)-4″-methoxy benzyl cinnamates was synthesized and studied with a view to understand and establish the effects of molecular structure on liquid crystal behavior. The series consists of eleven members of the series. None of the homologue derivatives are either nonliquid crystal or smectogenic, i.e. all the eleven members of the novel homologous series are enantiotropcially nematogenic only. Transition and melting temperatures as well as textures of the nematic mesophase were determined on an optical polarizing microscope equipped with a heating stage. The transition curves of the phase diagram show phase behavior in a normal expected manner. An odd-even effect is observed for the nematic-isotropic transition curve. The textures of the nematic mesophase are threaded or Schlieren as determined a by miscibility method. Analytical and spectral data confirm the molecular structures of the homologues. The average thermal stability for nematic is 213.8°C. The isotropic temperatures vary between 190°C and 240°C. The nematogenic mesophase length varies from 17°C to 102°C. Thus, the novel homologous series is entirely nematogenic without the exhibition of smectogenic character. The liquid crystal (LC) properties of the present novel series are compared with structurally similar other known homologous series.

A Study of Liquid Crystalline Properties and Their Relation to the Molecular Structure of Novel Ethylene Derivatives

A novel homologous series α-4-[4′-n-Alkoxy benzoyloxy] benzoyl β-4″-methoxy phenyl ethylenes of 12 homologue substances is presented and comprises of 5 compounds (heptyl to tetradecyl) that exhibit both a smectic and a nematic phases. The pentyl, hexyl, and hexadecyl homologues only exhibit the nematic without exhibition of any smectogenic property. The methyl to butyl homologues are not liquid crystalline. All novel liquid crystal (LC) substances of novel series are enantiotropically mesomorphic. The textures of nematogenic homologues are threaded or Schlieren and that of the smectogenic homologues are typical of the smectic A or C. Analytical and spectral data support the molecular structures. Solid-mesomorphic or isotropic, Sm-N, and N-isotropic transition curves of a phase diagram behave in a normal manner. An odd–even effect is exhibited by the Sm-N and N-isotropic transition curves. Thermal stabilities for the smectic and nematic mesophases are 118.0°C and 157.0°C, respectively. The Sm-N mesophase length is between 13°C and 21°C, whereas the N-I mesophase length varies between 20°C and 46°C. The liquid crystal properties of the novel series are compared with known structurally similar homologous series.

Synthesis and Study of Novel Liquid Crystalline Homologous Series: 4-(4′-n-Alkoxy Benzoyloxy)-3-Methoxy Phenyl azo-3″, 4″ Dichlorobenzenes

The synthesis and mesomorphic properties of a new homologous series of azomesogens, 4-(4′-n-alkoxy benzoyloxy)-3-methoxy phenyl azo-3″,4″ dichlorobenzene is detailed. The first four members of the series are nonmesomorphic, and the other eight members are smectogenic in character. The smectic mesophase, which is exhibited montropically, commences from the pentyl to the hexadecyl derivatives. The usual odd-even effect is observed in the isotropic-smectic transition curve. The isotropic-smectic transition curve behaves in a normal manner. The smectic mesophase shows a focal conic fan shaped texture of the smectic A type. An important feature of the series is the absence of the nematic property. The thermal stability and mesomorphic characteristic are compared with two structurally similar homologous series.

Synthesis and Evaluation of Liquid Crystalline Properties of a Novel Homologous series: α-3-[4′-n-Alkoxy Benzoyloxy] Phenyl-β-4″-Nitro Benzoyl Ethylenes

The titled homologous series consists of 11 members. The methyl and ethyl homologues are nonmesomorphic because of very high melting points, however, the propyl to hexadecyl derivatives are enantiotropic nematic with absence of smectogenic. The texture of nematic mesophase is threaded or Schlieren. The nematic-isotropic transition curve of the phase diagram behaves in a normal manner with the exhibition of an odd–even effect. The transition temperatures of the series and liquid crystal properties are observed through optical polarizing microscopy and a hot stage. The novel materials were characterized by elemental analysis, infrared, and 1H NMR spectroscopy. Analytical data support the molecular structures. The liquid crystal properties of the novel series are compared with structurally similar homologous series. The novel series is entirely nematogenic with absence of smectic character and of a middle-ordered melting type. The nematic-isotropic thermal stability varies between around 120°C and 180°C.

Functional characterization of dosage-dependent lethal mutation of ubiquitin in Saccharomyces cerevisiae

Ubiquitin is a eukaryotic protein with 96% sequence conservation from yeast to human. Ubiquitin plays a central role in protein homeostasis and regulation of protein function. We have reported on the generation of variants of ubiquitin by in vitro evolution in Saccharomyces cerevisiae to advance our understanding of the role of the invariant amino acid residues of ubiquitin in relation to its function. One of the mutants generated, namely UbEP42, was a dosage-dependent lethal form of the ubiquitin gene, causing lethality to UBI4-deficient cells but not to ubiquitin wild-type cells. In the present study we investigated the functional reasons for the observed lethality. Expression of UbEP42 in a UBI4-deleted stress-sensitive strain resulted in an increased generation time due to a delayed S phase caused by decreased levels of Cdc28 protein kinase. Cells expressing UbEP42 displayed heightened sensitivity towards heat stress and exposure to cycloheximide. Furthermore, its expression had a negative effect on the degradation of substrates of the ubiquitin fusion degradation pathway. However, UbEP42 is incorporated into polyubiquitin chains. Collectively, our results establish that the effects seen with the mutant ubiquitin protein UbEP42 are not due to malfunction at the stage of polyubiquitination.

Study of Mesomorphism Through a Novel Homologous Series and Its Relation to Molecular Structure

A novel homologous series 4-(4′-n-alkoxy benzoyloxy)-3-chloro phenyl azo,3″,4″-dichlorobenzenes was synthesized with a view to understand and establish the relation between mesomorphism and the molecular structure. The novel series consists of 12 members, which showed commencement of monotropic nematic mesophase formation from the butoxy homologue and continued up to the hexadecyloxy homologue without exhibition of a smectic mesophase. The textures of the nematic mesophase are threaded or Schlieren in type. Transition temperatures were determined by an optical polarizing microscope equipped with a heating stage. Isotropic-nematic transition curve of the phase diagram behaved in normal manner with exhibition of odd-even effect. Solid-isotropic transition curve behaved descending tendency by adopting zigzag path up to the pentyloxy homologue; which include methoxy to propoxy homologues as nonmesomorphic derivatives. Thermal stability for the nematic is just a few degrees (1°C to 2°C). Analytical and spectral data support the molecular structures. The mesomorphic properties of present novel series are compared with structurally similar other known homologous series.

The Ubiquitin Proteasome System with Its Checks and Balances

Cells need to quickly change according to changing environment to survive, and for that, they must not just make new proteins but also degrade others equally promptly. For this purpose, cells have evolved the ubiquitin system, which consists of ubiquitin molecules which are used to tag proteins in a process called ubiquitination; E1, E2 and E3 enzymes which carry out the process of ubiquitination; and deubiquitinating enzymes (DUBs) that remove the ubiquitin from the substrate proteins in a process called deubiquitination. Ubiquitination involves various lysine residues on ubiquitin; among them K48 and K63 are the most significant and well understood. Ubiquitination with K48 linkage leads to degradation of substrate proteins by a multi-protein complex called proteasome. Proteasome-mediated degradation is involved in numerous different processes in cells, due to which defects in it are responsible for several diseases. But due to the high diversity of E3 enzymes and ubiquitin target proteins, there are many drug targets that can be utilized to treat diseases. This makes it vital to understand ubiquitin system for advancement of health care.

Structural changes induced by L50P and I61T single mutations of ubiquitin affect cell cycle progression while impairing its regulatory and degradative functions in Saccharomyces cerevisiae

Posttranslational conjugation of ubiquitin to proteins either regulates their function directly or concentration through ubiquitination dependent degradation. High degree of conservation of ubiquitins sequence implies structural and functional importance of the conserved residues. Ubiquitin gene of Saccharomyces cerevisiae was evolved in vitro by us to study the significance of conserved residues. Present study investigates the structural changes in the protein resulting from the single mutations UbS20F, UbA46S, UbL50P, UbI61T and their functional consequences in the SUB60 strain of S. cerevisiae. Expression of UbL50P and UbI61T decreased Cdc28 protein kinase, enhanced Fus3 levels, caused dosage dependent lethality and at sublethal level produced drastic effects on stress tolerance, protein sorting, protein degradation by ubiquitin fusion degradation pathway and by lysosomes. UbS20F and UbA46S produced insignificant effects over the cells. All four mutations of ubiquitin were incorporated into polyubiquitin. However, polyubiquitination with K63 linkage decreased significantly in cells expressing UbL50P and UbI61T. Structural studies on UbL50P and UbI61T revealed distorted structure with greatly reduced α-helical and elevated β-sheet contents, while UbS20F and UbA46S show mild structural alterations. Our results on functional efficacy of ubiquitin in relation to structural integrity may be useful for designing inhibitors to investigate and modulate eukaryotic cellular dynamics.