Open Access Repository of Indian Theses

LAKSHMINARASIMHAN, K.S.V.

English

ELECTRICAL AND THERMAL PROPERTIESE OF SOME SEMICONDUCTORS

SONAWANE, HARIKISAN

BORON FLUORID CATALYSED ALKYLATIONS

MASSCARENHAS, A.F.


Abstract

Compared to living anionic polymerization, the use of radical polymerization methods appears more attractive from the point of view of ease of practice and the number of monomers capable of being polymerized. The evolution of techniques of controlled radical polymerization in recent years is an attempt to control the termination and transfer reaction leading to greater control over chain ends and polydispersity. Atom transfer radical polymerization (ATRP) has rapidly become one of the versatile methods in polymer synthesis. Copper catalyzed ATRP has been successively used in controlling polymerization of many styrenes, acrylates, methacrylates and several other relatively reactive monomers such as acrylamides, vinyl pyridines, and acrylonitrile. The objective of the present study is to examine the ATRP of methyl methacrylate (MMA) and other acrylates including styrene using Schiff base imines as N-donor ligands complexed with copper halide in conjunction with suitable initiators in order to achieve a controlled polymerization system. The study also involves a detailed investigation of a new tridentate N-donor ligand comprising batch, kinetic solvent, temperature, aging and substituents effects differing in electronic and steric property in ATRP. The other part of the study involves the use of novel initiators for ATRP. In the course of this investigation, ATRP of a vinyl ketone monomer, namely, methyl vinyl ketone was examined using an initiator which has structural similarity to the propagating radical. 

	The efficacy of a tridentate ligand, namely 2,6-bis[1-(2,6-diisopropyl phenylimino) ethyl] pyridine (BPIEP) on ATRP of MMA was studied. The optimum condition for BPIEP ligand was found to be 100: 1: 1: 2 ([MMA]: [EBiB]: [CuBr]: [BPIEP]) ratio at 90 oC in anisole as well as toluene (33 %, v/v) resulted in well-defined PMMA with a narrow molecular weight distribution. Systematic studies were performed with respect to nature and volume of thye solvent, initiator concentration, and temperature. The tridentate ligand, BPIEP, resulted in higher polymerization rates and initiator efficiencies at lower solvent volume. The rate of polymeirzation was slower with the tridentate ligand compared to a well-known bidentate ligand, namely, N-(n-propyl)-2-pyridylmethanimine (NPPI). The reverse ATRP of MMA using CuII/AIBN system showed good control in solution as well as bulk. The ligand was also successfully used for the ATRP of methyl acrylate and glycidyl methacrylate.

	The steric and electronic effects around metal center in atom transfer radical polymerization of methylmethacrylate at 90 oC using bis(imino) pyridine ligand was studied. Various tridentate N-donor molecules, having different steric and electronic environment were synthesized and characterized. Reducing the steric bulk on the ligand (BPIEP) results in loss of control in the polymerization of MMA. Kinetic studies of ATRP of MMA in toluene at 90 oC using N-((1E)-1-{6-[(1E)-N-phenylethanimidoyl]pyridin-2-yl}ethylidene)aniline) (NPEPA) resulted in curvature in the first order plot indicating termination reaction during the polymerization. However, using BPIEP as ligand resulted in PMMA ([M]/[I] = 800) with Mn,SEC = 15,600 with PDI = 1.16 and  high initiator efficiency of 0.85. Thus, the favorable effects of steric and electronic effect of the ligand on ATRP could be demonstrated.

	Four different unconjugated -diimines, and a bisoxazoline were examined as N-donor ligands in the ATRP of MMA in toluene at 90 oC using CuBr as catalyst and EBiB as initiator. None of the unconjugated -diimines gave acceptable polymerization behavior. A tridentate, bisoxazoline ligand (dmPYBOX) showed reasonable polymerization control for MMA under defined conditions.
 
	2-bromopropionitrile (BPN), 3-bromo-3-methyl-butanone-2 (MBB) and 3-(bromomethyl)-4-methylfuran-2,5-dione (BMFD) were explored as initiators for ATRP of MMA. All the three initiators gave controlled polymerization of MMA. The apparent rate constant (kapp) and initiator efficiency (Ieff) decreased in the order BPN > MBB >EBiB. MBB works efficiently with a bulky tridentate N-donor ligand, nmely, BPIEP. However, when used with well-known ligands such as, NPPI and dnNbpy, the polymerization results are not satisfactory.

	The efficacy of softer pseudo halogen (SCN-) as counterion in the initiator (R-X) as well as for catalyst (CuI-X) in copper catalyzed ATRP of MMA was studied. The chemistry of using thiocyanate both as counter ion for copper salt, CuSCN, and initiator, R-SCN, was based on the premise that CuSCN forms stable complexes with bidentate ligands. The redox potentials obtained for copper complexes were in the range suitable for ATRP catalysts. However, the catalyst system RSCN/CuSCN was ineffective for controlled polymerization of MMA and styrene.

	The feasibility of ATRP of methylvinylketone (MVK) was examined by varying the nature of ligands as well as initiators. Inability to polymerize MVK in the presence of copper catalyst was attributed to the presence of extended coordination of MVK with copper. 




BIOCHEMICAL STUDIES ON PLANT TISSUE CULTURAL: STUDIES ON VIQUA CATIANA CELLS

BATHISON, M. SAYAGAVER

Abstract
The technique of culturing plant cells in vitro has opened up interesting possibilities for studies of the mutritional requirements and metabolism of these cells the present study deals with the growth of opium (Papaver somniferum)cells tissue in vitro its nutritional requirements and the chemical analysis of some of the constituents of these cells explants of stemtissues were obtained from seeds of Papaver somniferum germinated under sterile condition the optimum condition for calls formation from the explants maintained on solid media were established using different media white's basal medium supplemented with yeast extract malt extract coconut milk and 2,4-dichlorophenoxyacetic acid and knop's basal medium supplements with white,s viramin mixture ferric citrate copper sulphate yeast extract malt extract coconut milk and 2,4- dichlorophenoxyacetic acid were the most effective. the callus cultures thus obtained were subcultured every fortyfive days on fresh solid media in this manner the tissue has been maintained successfully for 16 subcultrues on white's basal medium together with the above supplemets and 12 subcultures on knop's basal medium with the above supplements there was no diminution in growth of the cells during repeated subculture a truly viable in vitro culture of opium cells tissue has therefore been obtained. nutritional studies on the calls tissue indicated that the tissue fails to grow when either coconut milk or 2,4-dichlorohenoxyacetic acid was absent from the medium thus the tissue required both an auxia (2,4-dichlorohenoxyacetic acid or naphtalene acetic acid ) and coconut milk for good growth indole acetic acid was ineffective coconut milk could be replaced by kinetin but unlike coconut milk which acts synergistically with an auxiu kinetin can stimulate grouth in the presence of yesat extract and malt extract and does not require the presence of an auxia the effect of several other supplements on cell growth was tested and it was found that supplememtation of the basal salts -coconut milk yeast extract malt extract sorbitol (20mg/liter) and inosital (15mg/litre) resulted in the maximum growth of the cells different concentractions of sucress and coconut milk were tried two per cent sucrse concentration and ten per cent coconut milk concentration were found to be optimum growth obtained on white's basal medium with yeast extract malt extract ferric citrate copper sulphate coconut milk,2,4-dichlorohenoxy acetic acid was compared to that obtained with knop's basal medium supplemented with yeast extract malt extract coconut milk white's 'B' ferric citrate copper sulphate and 2,4-dichlorohenoxy acetic acid No difference was observed in the final weight of cells on the two media but with Knop's there was a reduction in the initial lag period of growth and the tissue was lighter in colour the opium cells were in general large with a cells size of 250 microns in length and 55 microns in width the tissue was dark brown or black in colour but at high auxin levels (10mg of 2,4-dichlorohphenoxyacetic acid per liter) the cells were pale yellow and translucent on subculture there was an initial lag period of 15 to 20 dyes after which there was rapid grouth for two to three weeks the tissue was also successfully grown in liquid medium without agar under submerged conditions on a rotary shaker the water content of the tissue was high (93 per cent). the total nitrogen content of the calls on a dry weight basis was 4 per cent of which one-sixth was alcohol-soluble nitrogen and teh rest was assumed to be protein nitrogen the total phosphorus content of opium cells was about o.4 per cent on a dry weight basis and the calcium content was 0.8 per cent alocholic extracts if tge calls tissue were analysed qualitatively by paper chromatography for amino acids non volatile organic acids sugars and alkaloides the following fifteen amino acids were tentatively identified in the tissue extract: glycine alamine valine leucine isoleucine serine threonine, aspartic acid, glutamic acid lysine arginine, phenyl alanine tyrosine, methionine and cysteic acid the presence of three unidentified ninthydrin-positive substacnes was also detected the tissue extract showed the presence of four non-volatile organic acids : citric malic fumaric and succinic and one unidentified acid three sugars namely: glucose fructose and sucrose were also identified no opium alkaloids could be detected on paper chromatography but four ultraviolet flourescing spots could be observed attempts to isolate these substances were abandoned as these could be obtained only in minute quantities chromatography on alumina however yielded adequate amounts of an ultraviolet absorbing material this was purified by fractional distillation in vacuum and was found to be an ester the acid isolated after hydrolysis had a melting point molecular formula and sublimation properties similar to phthalic acid the alcohol isolated after hydrolysis was not available in adequate amounts for further characterizations. 




IN VITRO CULCTURE OF PLANT CELLS STUDIES ON PAPAVER SOMNIFERUM L.

PETHE, LAXMAN

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ABSTRACT 
 
“Smaller is Better” is the dictum of the present day electronics. In this respect, the 
bandgap engineered silicon-germanium heterojunction bipolar transistor (SiGe HBT) 
technology has emerged as a viable candidate for a wide variety of electronic applications 
operating in extreme environments like space and high energy physics experiments. For 
future deep space probe applications and in the up-gradation of electronics in the ATLAS 
detector of LHC, CERN, one should show that SiGe HBTs can withstand high dose 
radiation. Therefore it is important and interesting to study the radiation tolerance on the 
electrical characteristics of 50 GHz and 200 GHz SiGe HBTs up to a very high total dose 
(100’s of Mrad). The irradiation time taken to reach such high total dose is very high with 
60Co gamma irradiation facilities. An alternate to 60Co gamma radiation is the high-
energy heavy ion irradiation. Therefore, the radiation tolerance of SiGe HBTs were 
studied using 60Co gamma radiation and different high-energy ions such as 50 MeV 
lithium, 75 MeV boron and 100 MeV oxygen ions up to 100 Mrad (Si) of total dose. The 
60Co gamma irradiation results were compared with the ion irradiation results in the same 
dose range of 600 krad to 100 Mrad. The I-V characteristics of un-irradiated and 
irradiated devices were measured using Keithley dual channel source meters model 
2636A and 2612A. The electrical characteristics such as forward mode and inverse mode 
Gummel characteristics, excess base current (ΔIB = IBpost - IBpre), current gain (hFE), 
damage constant (K), neutral base recombination (NBR), avalanche multiplication (M-1) 
and output characteristics were studied before and after irradiation. The base current (IB) 
of irradiated SiGe HBT was found to increase significantly after irradiation and in turn 
decrease the hFE. The electrical stress also creates damage in SiGe HBTs, similar to the 
radiation-induced damage. Therefore, mixed mode electrical stress effects were studied 
for 10,000 seconds. The irradiation results were systematically compared with mixed 
mode electrical stress results. Further, the recovery in the electrical characteristics of 
irradiated and stressed SiGe HBTs were studied by isochronal and electrical annealing. A 
unique bias condition was identified to study the electrical annealing of SiGe HBTs. The 
significant recovery in the I-V characteristics of SiGe HBTs were observed after 
annealing. The isochronal and electrical annealing results were compared and identified 
more recovery in the I-V characteristics after electrical annealing. The electrical 
characteristics of SiGe HBTs are acceptable even after 100 Mrad of total dose. The 
results of the present investigation will find applications in the field of space, high-energy 
physics, nuclear radiation environments and by device layout engineers. 


THE HIGH TEMPERATURE OXIDATION OF METALS AND ALLOYS

RANADE, A. C.

SPECTROCHEMICAL PROPERTIES AND THERMAL STABILITIES OF SOME TRANSITION METAL COMPLEXES

KEER, H. V.

LOW TEMPERATURE HEAT CAPACITIES AND THERMODYNAMIC PROPERTIES OF ANHYDROUS POTASSIUM FERROCYANIDE

SABANE, CHANDRAKANT

ABSTRACT 
 
This thesis explores the dispersion stability, microstructure and phase 
transitions in anisotropic nanodiscs with combination of experiments and theory. 
Phase behavior and distinct phases of individual and mixed states of nanoclay 
dispersions is discussed. Nanoclays of different aspect ratio have been used to 
explore the dynamics. Distinct phase separation, equilibrium fluid and 
equilibrium gel phases have been observed in nanoclay dispersions with aging. 
This thesis explores solution behavior, gelation kinetics, aging dynamics and 
temperature-induced ordering in the individual and mixed states of these discotic 
colloids. The formation of colloidal gel through different routes has been reported 
in this thesis. We study the anisotropic ordering dynamics induced by interface, 
waiting time and temperature in these dispersions. We also study aggregation 
behavior of nanoplatelets in hydrophobic environment of alcohol solutions.  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


STUDIES OF THE ELECTRICAL AND MAGNETIC PROPERTIES OF SPINEL-LIKE COMPOUNDS I: ELECTRICAL PROPERTIES OF SOME MANEGANITES II: MAGNETIC PROPERTIES OF SOME MANGANITES

LOBO, J

 Summary 
 
175 
 
The drug discovery and development process has undergone dramatic changes 
particularly in the last decade. Progress in drug discovery has been fueled by improvements in 
methodologies and technologies including automated HPLC, automated method development, 
LC-MS. LC-NMR and high-throughput purification methods. During the drug discovery and 
development process, rugged analytical methods are highly desirable to evaluate early drug 
targets, drug metabolism, pharmacokinetics, process research, preformulation and formulations. 
In view of the continuous demand for bioanalytical methods in drug discovery and impurity 
profiling method for maintaining the quality and safety of drugs; the present work has been 
proposed. The thesis has been divided into six chapters.  
Chapter 1 deals with a brief introduction to role of liquid chromatography in pharmaceutical 
analysis.  
Chapter 2 describes development and validation of a high-throughput LC-ESI-MS method for 
determination of an immunosuppressant drug sirolimus on dried blood spots using monolithic 
column. 
Chapter 3 deals with the synthesis of a molecularly imprinted polymer (MIP) followed by 
development and validation of a molecularly imprinted polymer based solid phase extraction 
method for determination of sitagliptin in rat plasma and urine.  
Chapter 4 describes the isolation and characterization of one of the potential process related 
impurities of phenazopyridine. 
Chapter 5 describes the enantiomeric separation and determination of adrafinil and its related 
substances. 
Chapter 6 discusses the evaluation of polysaccharide‐based chiral stationary phases for 
resolution of mirtazapine and its process related substances. 
 
 
 
 Summary 
 
176 
 
Chapter 1: Role of liquid chromatography in pharmaceutical analysis. 
This chapter gives a brief introduction to various roles of liquid chromatography in 
pharmaceutical analysis. In the modern pharmaceutical industry, HPLC is the major and integral 
analytical tool applied at all stages of drug discovery, development, and production. At each 
phase of development the analyses of varieties of samples are performed to adequately control 
and monitor the quality of the prospective drug candidates, excipients, and final products, which 
require bioanalytical as well as impurity profiling methods.  
Effective and fast method development requires a thorough understanding of HPLC 
principles and theory which lay a solid foundation for appreciating the many variables that are 
optimized during fast and effective HPLC method development and optimization. HPLC basics, 
types of chromatography, detectors, method development and validation are discussed in brief 
in this chapter. Hyphenated techniques such as LC-MS and LC-NMR were also discussed. In 
addition, a description of the specifics of the latest advancements in fast, chiral and other 
modern LC techniques are included. In lieu of continuous demand of bioanalytical and impurity 
profiling method, five drugs viz. sirolimus, sitagliptin, phenazopyridine, adrafinil, mitrazapine 
were chosen and following objectives had been set: 
A. Development and validation of a high throughput LC-ESI-MS method for determination 
of immunosuppressant drug sirolimus on dried blood spots using monolith column. 
B. Development and validation of a molecularly imprinted polymer based solid phase 
extraction of anti-diabetic drug sitagliptin in rat plasma and urine using zwitterionic 
hydrophilic interaction liquid chromatography (ZIC-HILIC). 
C. Isolation and characterization of one of the potential process related impurities of 
phenazopyridine. 
D. Enantiomeric separation and determination of adrafinil and its related substances 
E. Evaluation of polysaccharide‐based chiral stationary phases for resolution of mirtazapine 
and its process related substances 
 Summary 
 
177 
 
Chapter 2: Development and validation of a LC-ESI-MS method for determination of 
sirolimus on dried blood spots. 
Immunosuppressive agents are used to avoid rejection of transplanted organs by body 
immune system. There are various classes of immunosuppressive agents. Sirolimus belongs to 
mTOR (mammalian target of rapamycin) class of immunosuppressive agents which potently 
inhibit T-cell proliferation. Therapeutic index of sirolimus is narrow, so its blood level 
concentration needs to be analyzed regularly in ng/mL level in transplant patients. It is difficult 
for a patient to go regularly to clinic to provide blood sample for analysis. 
 In this chapter the suitability of a dried blood spot (DBS) technique was evaluated for 
sample collection. A patient can collect blood samples from finger prick on a blood spot card 
without much special training to a clinic for analysis. A high-throughput LC–ESI-MS method 
for screening of sirolimus on DBS was developed and validated. It involves solvent extraction 
of a punch of DBS followed by reversed-phase LC on a relatively new monolithic column 
consisting of a silica rod with bimodal pore structure and detection by ESI-MS.  
The analysis was less than 3 min with a very low backpressure at a flow rate of 0.5 
mL/min [Mobile phase A/B: 20/80, v/v; A: 0.01% (v/v) formic acid in water, B: methanol 
containing 0.01% (v/v) formic acid]. The method can analyze more than 100 samples in an 8 h 
working day, including sample preparation. The assay was linear from 1 to 100 ng/mL. The 
mean recovery was 92.42%. The mean inter-day and intra-day precisions were 1.23 and 1.41%, 
respectively.  
The developed method is simple, rapid and useful for clinical applications. The validated 
method was demonstrated to be accurate, precise, and robust and complied with the regulatory 
guidelines. Robustness of the method was tested by means of DOE technique. The stability of 
sirolimus on DBS samples stored in dark at 4°C for 90 days demonstrated that the samples can 
be stored for long periods of time before analysis. The effect of mobile phase flow rate on the 
performance of monolithic and particulate columns was also evaluated. 
 Summary 
 
178 
 
Chapter 3: Development and validation of a molecularly imprinted solid phase extraction 
method for determination of sitagliptin in rat plasma and urine. 
Antidiabetic drugs treat diabetes mellitus by lowering glucose levels in the blood. There 
are different classes of antidiabetic drugs. Sitagliptin (belongs to DPP-IV inhibitor class) is a 
relatively new drug approved for treatment of diabetes. The current methods for analyzing 
sitagliptin in blood and urine are not only time consuming and require expensive 
instrumentation but also affected by matrix effects and have low recoveries. Plasma 
phospholipids are one of the major contributing sources of matrix effects in protein precipitation 
based sample preparation techniques. 
 A novel water-compatible molecularly imprinted polymer was synthesized and used for 
selective solid phase extraction of sitagliptin in rat plasma and urine. The effects of progenic 
solvents, pH, cross-linker and amount of monomer were studied to optimize the efficiency and 
selectivity. The adsorption kinetics and isotherms were measured. The molecularly imprinted 
polymer (MIP) showed good specific adsorption capacity with an optimum of 180 mg/g at pH 
7.5 and selective extraction of sitagliptin from rat plasma and urine. The recovery of sitagliptin 
from rat urine and plasma was >98%.  
 
Figure: Synthesis process for sitagliptin imprinted polymer. 
 Summary 
 
179 
 
Sitagliptin is relatively a polar compound having high solubility in water and not retain 
properly on C18 column. Zwitterionic hydrophilic interaction liquid chromatography (ZIC-
HILIC) is a best choice to analyze such types of polar compound which were earlier cannot be 
analyzed without prior derivatization. The HPLC method was developed using Merck ZIC-
HILIC Column (100mm×4.6mm×5μm).Mobile phase, ACN and 15 mM ammonium acetate (pH 
4.5) 90:10,v/v. Analysis was carried out under isocratic conditions using a flow rate of 
0.4mL/min at 25°C. The chromatograms were recorded at 268 nm using a PDA detector. The 
limits of detection (LOD) and quantification (LOQ) were 0.03 and 0.10 μg/mL respectively. 
Chapter 4: Isolation and characterization of a potential process related impurity of 
phenazopyridine 
Drugs can be dangerous if there is no adequate control over their manufacture, storage 
and distribution. The impurity profile of a drug substance is critical to its safety assessment and 
its manufacturing process. Because the impurities are usually process related, they are most 
probably structurally similar to the synthesized target drugs.  
During the process development of phenazopyridine HCl bulk drug, a potential impurity 
was detected in the routine impurity profiles by HPLC. This impurity was collected using semi-
preparative HPLC. The semi-preparative HPLC was performed with Inertsil ODS 3V 
(10mm×250mm; particle size 5μm) column using water/ACN (30:70, v/v) as a mobile phase at 
a flow rate of 5.0 mL/min and the detector was maintained at 254 nm.  Using MS/MS and 
multidimensional NMR techniques, the trace level impurity was unambiguously identified to be 
3-phenyl-5-phenylazo-pyridine-2,6-diamine after its isolation from phenazopyridine HCl by 
semi-preparative HPLC. The formation of the impurity was discussed. 
 Summary 
 
180 
 
 
Figure: The mechanism of formation of the impurity of phenazopyridine. 
Chapter 5: Enantiomeric separation and determination of adrafinil and its related 
substances 
Metabolic and regulatory processes mediated by biological systems are sensitive to 
stereochemistry and different responses may often be observed comparing the activities of a pair 
of enantiomers. Chiral molecules are constituents of a large proportion of therapeutic agents, 
since the role of stereochemical factors in toxicity of chemotherapeutic drugs is vital. Analytical 
methods for controlling the enantiomeric purity of drug substances and their intermediates play 
a key role in the process of drug development.  
A rapid and reliable high-performance liquid chromatographic method for resolution of 
enantiomers of adrafinil, a novel vigilance promoting agent, and its synthetic intermediates was 
developed. The separation was carried out on a Chiralcel OJ-H colimn using n-hexane–ethanol 
(62:38 v/v) as a mobile phase. The detection was carried out at 225 nm using a photodiode array 
(PDA) detector. The optical rotation and order of elution of enantiomers were assigned using a 
polarimetric detector. Chromatographic parameters: retention factor (k’), resolution (Rs) of R-
(+)-adrafinil, S-(-)-adrafinil, I, II, III and IV on Chiralcel OJ-H wee also determined. The 
method is suitable not only for process development of adrafinil but also for quality assurance 
of bulk drugs and pharmaceuticals. 
 Summary 
 
181 
 
Chapter 6: Evaluation of polysaccharide‐based chiral stationary phases for resolution of 
mirtazapine and its process related substances. 
Mirtazapine is a tetracyclic antidepressant that finds widespread use as a racemate in the 
treatment of patients with severe depression. Investigations have revealed that the 
(S)‐enantiomer of mirtazapine has better potential in the treatment of depression because of its 
high binding affinity with α2-adrenergic, 5-HT2 and 5-HT3 receptors. Thus, the development of 
single enantiomers as a new active pharmaceutical ingredient is of great importance because 
biological systems interact with and metabolize them differently.  
High‐performance liquid chromatographic methods were developed for separation of the 
enantiomers of mirtazapine and its four process‐related substances  The direct separations were 
achieved on chiral stationary phases containing amylose tris(3,5‐dimethylphenylcarbamate) 
(Chiralpak® AD‐H), cellulose tris(3,5‐dimethylphenylcarbamate) (Chiralcel® OD‐H) and 
cellulose tris(4‐methylbenzoate) (Chiralcel® OJ‐H ). The experimental data were utilized to 
discuss the effects of the mobile phase composition, the nature of the alcoholic modifier and the 
specific structural features of the analytes on retention and separation. The elution sequence was 
determined under the optimized separation conditions. 


STUDIES ON THE UTILIZATION OF FLUORINE OBTAINED IN THE EFFLUENTS OF THE SUPERPHOSPHATE INDUSTRY

Vemulapalli, S. Phani Babu

Development of Solid- and Solution State NMR Spectral Simplification Methods for Complex Organic Molecules

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