Annual Report 2007-2008

Support to R & D Projects

The Department under the SERC R&D programme sanctioned during 2007-08, 495 Science and Engineering R&D projects at a total cost of Rs 13188.7 lakhs. The discipline-wise and institution-wise break-up of project support is given in Figures 2.2 & 2.3.

R&D Projects sanctioned during 2007-2008 (till 31st December, 2007)

Special emphasis has been given to the monitoring and evaluation mechanism of research programmes so as to asses the quality of work and research output. Several Group Monitoring Workshops have been organized in various disciplines in this period.

The broad discipline wise details of the achievements are as follows:

Chemical Sciences

Support to frontier areas of research continued as before. Launching of major programme on “Metal based drugs including leads from traditional medicine”, and identification of a few areas in the interface of “Organic Chemistry- Biology- Pharma” were highlights of the year. Programme Advisory Committees were reconstituted and a new team of experts were involved in assessing and reviewing R& D projects. Organic Chemistry Organic Chemistry-biology-pharma interface meeting was organized with the objective of identifying scientifically challenging and industrially important research topics in this important area. About 30 researchers from academia, national laboratories and industry participated in the meeting. A few areas were identified and proposals are being invited to undertake collaborative research. The identified areas are: (i) glycochemistry and biology; (ii) post translational modification; (iii) transcription control by small molecules; (iv) natural products; (v) infectious disease; (vi) metabolic disorder; and (vii) miniaturized protein moiety.

A “Repository for Organic Compounds” is planned. All the compounds synthesized in projects will be kept in the repository. The repository will have facilities for storage, purification, generation/retrieval of data and biological screening.

Apart from the above special initiatives, several projects in contemporary areas were supported. These were aimed at one or more of the following: synthesis of new molecules having either medicinal properties or materials applications; development of new methodologies; development of chiral catalysts; use of green protocol; self assembly of organometallic bioconjugates; study of polymorphism etc.

Several interesting results have been obtained from ongoing projects. Some of these are:

• Enantioselective total syntheses of a few indolizidine alkaloids have been achieved using epoxy-azide cyclization as a key step. A novel domino epoxy-olefin-azide cyclization method has been developed for the stereo- and enantioselective synthesis of azapolycyclic ring systems. For the first time, azide has been used as a novel terminating group in polyene cyclization.
• An exclusive organo-base, 1,1,3,3-tetramethylguanidine(TMG) promoted Cannizzaro reaction has been reported for the first time. Although this reaction is applicable only to reactive aromatic aldehydes, the work provides new perspectives and avenues for further understanding the applications of Cannizzaro reaction.
• 1,2-Functionalization of alkenes with azide and halogens (haloazidation) represents an important transformation in organic synthesis. Metal triflate catalyzed 1,2-bromoazidation of alkenes was performed using N-bromosuccinimide (NBS) and trimethylsilyl azide (TMSN3) as the bromine and azide sources, respectively. This catalytic process represents a highly regioselective, stereoselective and high yielding
  method for the synthesis of anti-1,2-bromoazides from a variety of alkenes including á,â-unsaturated carbonyl compounds. A versatile and highly efficient protocol for the synthesis of 1,5-disubstituted tetrazoles has also been developed by metal triflate catalyzed one-pot reaction of alkenes, NBS, nitriles and TMSN3.
• A highly efficient, flexible and convergent route has been developed to prepare cis-2,3,6-trisubstituted piperidines employing Sharpless asymmetric aminohydroxylation and stereoselective reductive amination as the key steps.
• An efficient and a convenient enantioselective synthesis of (3R,4S)-3-methoxy-4-methylaminopyrrolidine has been carried out by a lipase-mediated resolution protocol. This method describes the preparation of (+ -)-1-Cbz-cis-3-azido-4-hydroxypyrrolidine starting from commercially available diallylamine followed by ring-closing metathesis (RCM) via SN2 displacement reaction. Pseudomonas cepacia lipase immobilized on diatomaceous earth (Amano PS-D) provides (3R,4S)-11 and (3S, 4R)-12 in an excellent
  enantiometric excess.
• It has been shown that carbohydrate-based starting materials can be utilized for diversity oriented synthesis (DOS) pathway development. At least 400 compounds with 15 scaffolds which are novel, chiral and complex small molecules have been successfully synthesized. These molecules will be screened for variety of disease targets.
• A facile multicomponent reaction has been unraveled which offers a convenient entry into the synthesis of highly substituted cyclopentenone derivatives. The reaction is especially noteworthy since this is the first multicomponent reaction involving the dimethoxy carbene-dimethyl acetylenedicarboxylate zwitterion leading to the formation of carbocycles.
• A series of novel viologen linked pyrene derivatives were synthesized and their photophysical and DNA binding properties were studied. These novel bifunctional systems have potential use as photoactivated DNA cleaving agents that can function purely through a co-sensitization mechanism. In addition, a series of 9-substituted aryl acridinium conjugates were also synthesized and their photophysical and DNA binding abilities were studied. The conjugate containing ortho-substituent was found to distinguish between ssDNA and dsDNA through changes in fluorescene intensity and hence can have potential applications.

Inorganic Chemistry

A major programme on “Metal based drugs including leads from traditional medicines” was launched. A total of seven proposals were recommended for support under this programme. The proposals target four diseases, namely, cancer, ulcer, diabetes and arthritis. The aims of the proposals are:

• Synthesis of functionalized phosphine based metal complexes with suitable links to the appropriate small molecules (biotin, folic acid and small peptides) which are to function as “magic bullets” and study their anti-cancer activity.
• Synthesis and characterization of a variety of redox active 3d-transition metal complexes and cis-platin conjugates having photosensitizing ability at visible light, and study their DNA binding and cleavage properties. This study attempts to find alternative to existing drug (Photofrin) for the treatment of cancer by photodynamic therapy.
  
• Development of new and novel infrared absorbing dyes based on squaraine, croconaine and expanded porphyrins and their metal complexes which can have potential application as sensitizers in photodynamic therapy (PDT) of cancer and other diseases
  
• Synthesis of steroid linked and non-steroid linked metal complexes containing Cu(II), Ni (II), Pd(II), Pt(II) and Zn(II). These metal complexes will be characterized and will be investigated for their potential anti-cancer activities.
• Synthesis of ruthenium based compounds and elucidate molecular mechanism of action so as to provide information as to how they induce anti-tumor effects.
  
• Synthesis of some arsenic-amino acid complexes and study them with a view to understand arsenic toxicity. Some bismuth based compounds are also proposed to be synthesized and these compounds will be investigated for their efficacy as anti-ulcer drugs.
• Scientific validation of safety and efficacy of Tamira Parpam, a herbomineral preparation of siddha medicine containing copper in the management of ulcer. Efforts will be made to characterize active copper species responsible for the action of drug.
  

In addition to the major programme mentioned above, several projects in frontier areas were also funded. Progress of many ongoing projects was reviewed, and most of them resulted in high quality publications in internationally reputed journals. Some interesting results obtained in the ongoing projects are:

• Two series of lanthanide benzenedicarboxylates of the general framework formula [M2(2,2’- bipy)2(C8H4O4)3] (M = Y, Gd and Dy), have been prepared employing hydrothermal methods and their structures determined by single crystal X-ray diffraction. Both the structure types contain only one type of secondary building units (SBU), which are connected differently giving rise to two- and threedimensional structures. While the two-dimensional structure is related to an augmented square lattice, the three-dimensional one closely resembles the CdSO4 structure. This is the first observation of a CdSO4 structure, in the coordination polymers containing rare earth ions.
• Pd, Au and Ag precatalysts of various new N-heterocyclic carbenes have been designed. These precatalysts have shown remarkable activities towards C-C bond forming reactions as well as towards the ringopening polymerization (ROP) of L-lactide. The author reported the first example of a gold based initiator for the ring-opening polymerization of L-lactide.
• Several platinum metal complexes that are suitable for mediating C-H and C-C activation have been synthesized. Some selected organic molecules have been observed to undergo facile C-H (and in some cases C-C) bond activation upon their reaction with platinum metal compounds leading to the formation of interesting organometallic complexes. Unusual migration of alkyl group and transformation of coordinated ligands have also been observed.
• In a project on development of general procedures for the synthesis of optically active cobaloximes, hindred rotation leading to nonequivalence in 2-substituted benzyl cobaloximes was noticed. Benzyl cobaloximes with substituents at 2-position having varying electronic and steric properties and with three different dioximes (dmgH, dpgH, gH) were synthesized and characterized. The nonequivalence has been rationalized in terms of restricted rotation of the Co-C and/or C-Ph bond and is attributed to weak interactions between axial and equatorial ligands.
• New structural forms of organostannoxane clusters have been isolated and characterized. These compounds have been successfully utilized as supports for multi-electro active, multi-site coordination and multiphotoactive assemblies. Cyclophosphazene multi-site coordination ligands have been used for building new hybrid main-group-metal architectures.
• Several 3d-metal (copper, iron, vanadium, cobalt, nickel and zinc) complexes having DNA binders and photosensitizers have been synthesized and characterized. Control DNA cleavage experiments were performed. A iron complex showing DNA cleavage in visible region has been reported for the first time.
  

Physical Chemistry

Some of the sanctioned projects are as follows:-

• Time resolved spectroscopic investigation of excited state processes in neat solutions and microheterogeneous media;
  
• Synthesis, structure and photocatalytic properties of aluminophosphates (AIPOs) and related materials;
  
• Heteropoly acids supported on titania and mesoporous materials as catalysts for acid and redox organic transformations;
  
• Intercalation chemistry of anions clay: Possible applications in separation of anions, organic synthesis and preparation of layered composites;
  
• Mechanisms of photochemical reactions in ionic liquids;
  
• Search for new photocatalysts for the degradation of toxic organics utilizing visible radiation;
  
• Development of new magnetically active transition metal molybdates;
  
• Countorion binding-interfacial property correlation for AOT micelles;
  
• Novel nanocomposite polymer electrolytes for lithium batteries;
  
Optical materials based on molecular assemblies in colloid, thin film and solid state;

• New methods and techniques for solid state NMR spectroscopy: Rapid data collection and application to biological systems;
  
• Optical nonlinearity and solution structure of molecular complexes by depolarized Hyper-Rayleigh scattering;
  
• Novel approach towards the synthesis of nano-membranes for the separation of gases: Structure-property relationships in organosiloxane based polyurethanes and imides; and
  
• Electronic structure and properties of atomic nano-clusters.

The salient achievements from the ongoing projects are:

• In a project on photochemistry of ionic liquid, it has been shown for the first time that imidazolium ion based ionic liquids have non-negligible absorption in the UV-region and are weakly fluorescent and the planarity or the polarizability of the cationic component was not responsible for the ultrafast component of the solvation dynamics.
  
• A 300 MHz EPR Imaging system has been constructed using individual modules (magnet, gradient coil, lock-in-amplifier) and in-house fabrication of some components. The performance evaluation of the EPR spectrometer was done using TEMPOL and DPPH as spin-probes. A phantom with two capillaries, one containing about 1 mg and the other about 0.06 mg of NMePyTCNQ was imaged. A solenoid coil using copper strip which could be tuned to Q of about 1500 has been constructed. The sensitivity of the spectrometer has been tested using this coil to measure the signal-to-noise ratio of the EPR spectrum of the nitroxide spin probe, TEMPOL in water. A novel reconstruction technique for EMR imaging using artificial neural network has also been developed for the first time. Image reconstruction by the trained neural network shows better time complexity than the conventional iterative reconstruction algorithms.
  
• Vibrindole A has been synthesized successfully for the first time in the presence of zeolite in good yield. Novel route to produce thymol by vapour phase reaction of m-cresol with isopropyl acetate over Al-MCM-41 has also been reported.
  
• Gas phase hydrogen bonded clusters of phenylacelylene with various solvents have been investigated using laser induced fluorescence and IR-UV double resonance spectroscopic methods to understand the intermolecular interactions of dihydrogen complexes. The study reveals that the acetylenic CH group of phenylacetylene does not interact with common bases to form a hydrogen bond. It also reveals that triethyl-germanium-hydride form a Ge-H—H-O di-hydrogen bonded complex with phenol, and this is the first report on dihydrogen bonded complexes involving germanium hydride.
  
• In a project on development of soft computing techniques, (i) genetic algorithm driven methods for solving Schrodinger equation with hydrogen molecule ion; (ii) a local energy based GA method for solving one, two and three-dimensional Schrodinger equation, and (iii) a method for determining molecular electronic structure of doped polythiophene oligomers containing up to 100 units under zero band gap constraint have been developed. The codes for these applications have been parallelized and tested. The
  investigator has also developed a method using single particle density based simulated annealing strategy for finding global minimum on the potential energy surface of neutral polythiophene oligomers.
  
• In a project on molecular electronics, design and synthesis of functional transport-active fullerene C60 based donor-bridge-acceptor molecular junction (Dyad) has been prepared which has the potential for use as molecular resonant rectifier.
• Detailed charge density studies on a few carefully selected alkali and alkaline metal sulfates at different temperatures were carried out to obtain a fundamental understanding of phase transitions. Phase transitions in a series of hydrogen sulfates (Rb3H(SO4)2, (NH4)3H(SO4)2, K3H(SO4)2, and Na3H(SO4)2) have been evaluated based on single-crystal structure analysis. This study revealed the exact nature of transitions and sorted out various ambiguities present in the earlier literature. It has been found that the distortion of the SO4 tetrahedra and the coordination around the metal atom sites control the phase evolution in the Rb compound, while the Na and K analogues show no phase transitions at high temperature. It is also revealed that the NH4 system transforms to a higher symmetry space group resulting in a disorder of the sulfate moiety.

Green Chemistry

Two workshops were organized at National Environmental Engineering Research Institute (NEERI), Nagpur and at National Institute of Pharmaceutical Education and Research (NIPER), Mohali, to generate awareness of ‘Green Chemistry’ among researchers and industry representatives. Around 150 researchers attended each workshop. The outcome of the workshops formed a significant input in preparing a monograph on “Green Chemistry Experiments”. The monograph, written in a pedagogical manner contains many laboratory experiments for under-graduate and post-graduate chemistry students. These “green experiments” do not use hazardous chemicals, and provide good alternative to the existing hazardous experiments currently in practice in many universities. The following projects were funded:

• Development of biodegradable plastics for packaging applications by blending natural polymers (tapioca starch, cellulose, lignin, rubber wood flour and chitosan) as fillers with synthetic polymers (LDPE, PS, PET and PMMA). The emphasis is to obtain biodegradable polymer having high percentage of LDPE.
  
• Development of completely biodegradable polymer composites with natural polymers like soya bean floor as reinforcement and natural uniaxial oriented fabric Hildegardia as reinforcement. Mechanical parameters will be determined. The effect of different enzymes on biodegradation of the composites will also be studied.
  
• Enhance biodegradation of polypropylene (PP) using biosurfactants. This proposal attempts to study whether by increasing the rate of production of biosurfactant (produced by soil organisms), one can increase the rate of biodegradation of PP (not pretreated and thermally pretreated polymer). The biosurfactant production will be enhanced by manipulating pH, temperature, addition of cations (Mn, Fe), and nitrogen source such as urea.

The progress of a few projects was reviewed and two patents have been filed in a project. One patent was for developing a process for making slow-release phosphate fertilizers and another for developing an ecofriendly process for making Epsom and Gypsum.

A meeting with pigment based industrialists and researchers were organized at Ankleshwar to know the problems faced by the “pthalocyanine based pigment industry” and provide possible technological solutions to those problems. Four problems have been short listed. They are (i) substitute for aluminum chloride in the production of crude CPC; (ii) substitution of 16 atoms instead of 15 in the chlorination process; (iii) recovery / replacement of aluminum molybdate catalyst; and (iv) reduction / replacement / disposal of sulphuric acid. Further discussion with pigment industry is in progress.