VISION FOR R&D IN CHEMICAL SCIENCES
Government of India ,
Ministry of Science & Technology
Department of Science & Technology
New Mehruali Road,
New Delhi 110 016
Department of Science & Technology is promoting research in frontier and emerging areas through the Science & Engineering Research Council (SERC). SERC is composed of eminent scientists, professionals and technologists drawn from various universities, national laboratories and industries, and is assisted by a large number of Programme Advisory Committees (PACs) in various disciplines. SERC has evolved, over the years, a unique peer review system which has been well-recognised by the scientific community. It has helped in promoting and strengthening of several new areas of research and established a large number of national research facilities, core groups/centres. It also endeavoured to promote the new concept of strengthening research capabilities in relatively small and less endowed universities/departments to increase critical mass.
The Council has recently reviewed its activities and areas of research which were earlier identified and has decided to update the areas for future support. Under the overall supervision and guidance of SERC, PACs in various disciplines have been requested to prepare to state-of-the-art document called "Vision for R&D" reflecting new challenges to the scientific community, national facilities to be set up including new ways and mechanisms of their promotion.
It is with this background that the Department of Science & Technology has decided to give wider publicity to these areas for promoting them in future. This document titled, "e; Vision for R&D –Chemical Sciences" is for those who are interested in vigorously pursuing research in Chemical Sciences. It is hoped that this document would be useful to the scientific community in planning their future research activities.
The profile of organic chemistry in the next decade would be based largely on the outcome of endeavours of the present decade. It is but natural to assume that those leads which are saturated will not be pursued. The focus of the present paper would therefore be on active areas in vogue and the new disciplines that may emerge which will have great impact in areas like food, health care, energy, materials and environment. The challenges for organic chemists to meet the above criteria are not only important but also provide excellent opportunities towards innovation in basic research with direct impact on society.
Petroleum - based
Renewable, Non-toxic non – renewable
(21st century) (20th century)
Industrially Important Organic Compounds
Chemical Enzymatic Genetic
modification modification engineering
Highlights of 21st Century Industrial Requirements
The vision of organic chemistry can therefore be perceived from the standpoint of the state of the art of the subject under the following broad categories : (I) Synthesis (II) Materials and Surfaces (III) Interface of Organic chemistry with Biology and (IV) Theory.
(a) (i) Covalent Synthesis
Organic Systhesis is the crossroad of several other subdisciplines. It can be viewed as the means, the end or the beginning depending on the type of objective, viewpoint, or the project. The range of organic synthesis has been greatly influenced by the increasing ability to address molecular complexity and has evolved from largely empirical approaches to sophisticated strategies. "Practicality" should play an important role in defining the impact of synthesis, however, such syntheses are not common. The ideal synthesis is one in which the target molecule (natural or designed) is prepared from readily available, inexpensive starting materials in simple, safe, and resource-effective operation that proceeds quickly and in quantitative yield. Today it is not only a question of what we can synthesize, but how we do it. Major problems in chemical production are the handling of wastes, the search for environmentally tolerable procedures etc.
Emphasis should be placed on brevity of operations and simplicity of design, unless of course a new technology offers unprecedented advantages over the existing methods. It is likely that this new technology will be adopted from another discipline such as molecular biology, microbiology, material science etc. The future direction of synthesis will therefore depend on multidisciplinary efforts. Ventures into seemingly unrelated areas in search of a solution to a synthetic problem are to be encouraged for these provide the most imported advances.
Research in this field is undergoing rapid technological changes and takes place in an industry experiencing increasing commercial and regulatory pressures. Regulatory requirements have eroded the effective patent life of new agents with profound effects on revenues from new drugs / molecules. The priority now is cost effective development of novel agents in areas of currently unfulfilled medial needs and in shortest possible time.
The synthesis of compounds using combinatorial chemistry is beginning to make a significant impact on many branches of chemistry. By throwing away some of the long held beliefs about the practice of organic synthesis, the process of combinatorial chemistry now permits the production and assessment of "libraries" of a large number of compounds in the time previously taken to make a single compound. This is a technology through which large numbers of distinct molecules may be synthesized in short time and resource effective manner and then efficiently used for a variety of applications.
In the past few decades structural organic chemistry has been largely concerned with covalent interactions. Although necessary, the preoccupation here curbed the understanding of non-covalent intercations, which play a critical role in life systems. There has been a great deal of activity during the past two decades in the general areas of supramolecular chemistry – defined by Lehn as ‘chemistry beyond molecules’. In the future, research in this area is likely to intensify for making supramolecular systems that can function. Broadly, the following areas will be of relevance in the coming decade.
The chemistry of natural product strongly rooted in India, would witness resurgence for a variety of reasons. An area that would and should witness growth is the application of methodologies available in the domains of chemistry and biochemistry, to products that are of social relevance, from naturally occurring substances devoid of any problems.
The advent of modern methodologies has enabled the isolation and characterization of even the most minor components produced by the plant kingdom. The erstwhile practice of chemical taxonomy largely focused on major compounds that are water insoluble. In retrospect, these efforts, although of great importance, overlooked minor and water-soluble constituents having good application potential. Several plant species that merit such a detailed examination based on the known knowledge of their application and ethnobotanical information.
II Materials and Surfaces
The chemistry of organic / organometallic materials, both small molecules and polymers, is a major scientific theme that would unite broad areas of research in the future. Two of the broad objectives of this area are (i) understanding the macroscopic properties of matter based on the knowledge of its molecular structure and (ii) preparation of new and novel materials to perform specifically designed functions. A better understanding of the relationship between structure and properties of materials is emerging, and is bound to result in new materials, that along with micro-fabrication techniques will lead to miniaturization (nanotechnology) of devices. The tough physical and mechanical properties of biopolymers has inspired new design of molecular and composite materials with desirable properties.
The ability to deposit thin films of organic materials on inert surfaces is opening up vast possibilities in the domains of memory storage systems, light and mechanically induced switching devices, conducting materials and power generating systems. Therefore, the chemistry of thin films of organic materials should advance in the coming years.
III Interface of Chemistry and Biology
The interface of organic chemistry with biology is undoubtedly going to be the most important discipline in the coming years. The initiatives will henceforth lead to newer understanding of fundamentals that promotes the discovery of newer therapeutic strategies, diagnostic tools and biomaterials. Understanding of genes and genomic functions at molecular level would allow the alteration of bio-functions in a desirable and predictable manner.
One of the important areas that is fast emerging and needs considerable organic chemistry expertise is the molecular design of bioconjugates. These molecular hybrids are structural combinations of two or more bioactive subunits. Depending on the nature of components these conjugates will have diverse applications ranging from significantly enhanced bioactivity to delivery / targeting of drug and diagnostics. Given the choice of structural permutations that can be generated from biological monomers and active pharmacophores, this area has abundant future for organic chemists.
Successful delivery of drugs to their specific targets within a reasonable time and level of bioavailability is an important aspect of management of toxicity side effects. In particular, the concept of controlled delivery systems endowed with targeting functions demands design of biocompatible and stable matrices.
Biomimetics are functional mimics of biological systems. Construction of such mimics can lead to a better understanding of the biological complexity at a molecular level. Such biomimetics can include chemzymes, artificial nucleases, ribozymes, ionophores, peptidomimetics etc.
Nature ingeniously employs membrane environments for selective surface recognition. Traffic of small molecules across either side has an important regulatory function for the cell. Lessons learnt from such natural processes will have significant impact in the future design of membrane like scaffolds.
IV Theory and Computational Organic Chemistry
The practice of organic chemistry has dwelled largely in empirical domains, where the odds of a new reaction pattern proceeding in a directed way is rather slim. In contrast, in Nature, as a product of evolution, reactions proceed smoothly along the desired path. Even the simplest of chemical reactions defy logical analysis form a practical point, since many parameters such as media, reaction conditions and other factors generate several possibilities. Significant theoretical modeling, taking these into account, is the need of the hour and such studies would help design of directed organic transformations. A systematic thermochemical analysis of each step of a complex reaction pathway should enable the prediction of optimum conditions for each step. The coming years should also see a more efficient use of physical organic chemistry concepts for the analysis of microenvironmental effects of organic reactions. These assume enormous significance of logical understanding of both homogenous and heterogeneous catalysis. Study of microenvironmental effects on binding constants of interacting molecules and their thermochemical analysis, deciphering of the role of water molecules in mediating molecular recognition assume importance in the design of better molecular recognition systems.
In the vision paper on organic chemistry a number of areas where there is a lot of activity at the present time, and areas where there is likely to be more activity in the future have been indicated. Considering the present scenario and the status of organic chemistry in India it is possible to work out strategies which will facilitate the realization of the vision of the future.
One of the important strategies to be adopted will be to strengthen areas of activity for which already some expertise is available in the country. The second strategy should be directed in identifying new areas (envisioned in the document) in which very little, if any activity is taking place and initiate infrastructure and core group for building up such activity.
Work on organic synthesis and natural products has been the mainstay of organic chemists in India in the past decades, and from the record of publications in international journals in recent year it is clear that the expertise available in these areas should be guided and nurtured along emerging new interests (synthesis of designer molecules, bioassay-directed natural products work etc.). Similarly, some activity (although small) exists in the area of non-covalent synthesis (supramolecular chemistry) and this activity should be strengthened along the lines suggested in the vision paper.
II Identification of new emerging areas and build up of facilities:
In the following important areas practically no work has been initiated by organic chemists in India (except in one or two groups). Existing expertise in related areas can be/should be utilized to initiate new research activity in (a) combinatorial chemistry, (b) molecular design of bioconjugates, (c) organic chemistry of surfaces, (d) DNA recognition and cleavage systems, the design of DNA – dependent enzyme inhibitors, (e) glycoconjugates and immunomodulators, (f) organic materials – NLO materials, nanomaterials and MOCVD materials.
Here also 10-12 individuals/research groups/departments/institutions should be identified/invited to write proposals as interdisciplinary activity and create new instrumentation facilities to initiate the work.
Over and above the ones mentioned earlier it is good to identify researcher/groups in less endowed institutions who have the capability but are working in less challenging areas. Making them aware of the future directions, and encourage and support them to initiate work in emerging areas.
To arrange frequent meetings/workshops for researchers around the country ("Organic Chemistry Update") as a general awareness program.
Encouraging graduate and postgraduate departments around the country to upgrade their curriculum to make the courses/programs more exciting and up to date.
Provide full support to Project investigators to present paper in one international conference in the second or third year of the project. This will certainly help the investigator `globalize’ his work, and will also help him/her stay abreast of recent developments. This will certainly assist the investigator to write a more challenging program for the next proposal.
The following equipments are now standard in any organic chemistry department actively involved in research. Therefore, it is recommended that an all-out effort is made at the national level to upgrade the infrastructure in universities/institutes/research laboratories which have been carrying out high-quality organic chemistry research at least during the past ten years. Perhaps 10-15 such places could be chosen at the first phase.
High field multinuclear NMR Spectrometer
Preparative HPLC systems
CD-ORD with LD attachment
Molecular Modeling hardware/software
UV spectrophotometer with diode array detection
Initiating New Programs
These equipments are needed for starting new programs, specially in the interdisciplinary areas. Not every laboratory need to be equipped with all of these, but it must be ensured that there are at least four to five centers in the country in which all these equipments will be available to researchers supported by DST funding.
Combinatorial library synthesizer
Langmuir-Bloddget film balance
Droplet counter-current extractor
Quasi-elastic laser light scattering equipment
Differential scanning calorimeter
Fluorescence lifetime measurement units
NLO measurement equipment
High-performance capillary electrophoresis equipment
Fast kinetics measuring equipment
The natural diversity of inorganic chemistry has endowed an inherent interdisciplinary bias to it. With passage of time the cross culture has become progressively stronger and in the coming years one can anticipate an even stronger influence of inorganic chemistry in the development of other areas such as biology and material science. The role of inorganic chemistry.
In the industry has been well substantiated in the generation of wealth. The projected research and development areas in inorganic chemistry can be logically cast into six parts each of which is elaborated in the subsequent sections.
The goals of inorganic chemistry in India for the coming decades can be stated as follows.
The possible approaches for accomplishing the stated goals are outlined below.
Synthesis and Structure
Designing and synthesizing molecules constitute the primary hub of activities in inorganic chemistry. For keeping up intellectual curiosities alive, it is essential to search for exotic or esoteric molecules and systems. These will actually turn out to be `useful on a long term basis. The systems include small molecules, unusual large species, bioinorganic models, molecular wires, mesomolecules, supramolecular assemblies and the like. The challenge here is self-evident and the utility of the systems spans cardinal areas such as catalysis, magnetic exchange, solar energy harvesting, molecular electronics and material science.
The synthetic chemistry of rare earths and actinides, especially materials of high purity, should be encouraged in view of their relevance to energy needs as well as the abundance of the relevant minerals in India. The synthesis and application of colloids based on metal hydroxides, oxides and large anions are exciting areas for development. Modern synthetic techniques involving solgel methodology, high vacuum vapour deposition, laser ablation and other unusual routes deserve greater attention. Novel synthetic methodologies for compounds of transition and main group elements need to be explored and promoted.
A detailed structure determination is synergic with synthesis and hence will act as a feeder to newer synthesis. More complex and more intriguing the molecules are, more scrutinizing and exacting will be the methods for characterizing their molecular and electronic structures. These studies would involve diffraction, magnetic and spectroscopic investigations. There will be two levels of sophistication in structural studies; one is required at the immediate vicinity of synthetic place and other at the hands of experts. Just as the diffraction techniques have become more easily accessible to the inorganic chemists in recent years, techniques for measuring detailed and in depth magnetic, electronic and optical measuring down to 1.2 K should be accessible at least on a limited but at a cooperative endeavour. It may also be understood that some of the newer molecules may not crystallize and would therefore need better structural techniques such as EXAFS and FABMASS. Similarly, in order to probe small particle sizes more powerful microscopic techniques such as AFM will be needed. Investment on structural measurement instruments and facilities is an important prerequisite for successful operation of meaningful projects.
Reactivity and Catalysis
Reactivity studies in inorganic chemistry are as important as those of syntheses of novel molecules. Mapping general patterns of chemical reactivities of transition metal complexes as well as of compounds of non-transitional elements is an emerging and fascinating area. The roles of nuclear factors and electronic effects in reactivities following thermal and photochemical excitation need to be quantified. Chemical transformations of molecular systems including those of coordinated ligands and fluxional species form an important area of research. Reactions involving transfer of electrons, atoms and groups as well as energy are exciting and these include the not well-understood segments of the photosynthetic pathway. Physical models for the description of substitution and long range electron and energy migration processes are of much interest.
The reactivity of ligands can undergo a dramatic change upon coordination to a metal atom. This in fact is a principle behind the action of many metalloenzymes and homogeneous catalysts. The variable oxidation states of transition metal ions are essential perquisites for the electron transfer chains in biological systems. Research encompassing a variety of such systems and time-scale has been and will continue to be an active area of research. Industrial and bio-catalysis have already gained high significance.
Inorganic chemistry plays a pivotal role both in heterogeneous and in homogeneous catalysis. A major advancement in heterogeneous catalysis-the use of natural or synthetic aluminosilicates, aluminophosphates and transition-metal doped similar materials with novel structures-has opened up possibilities of highly selective organic transformations. New and rational methods of synthesis of a wide variety of mesoporous solids will make it possible to apply some of these materials for organic transformations that have so far not been amenable to heterogenous catalytic treatments. Rapid progress is possible here because of the advancement in the structure determination techniques such as CPMAS, solid-state NMR and high resolution electron microscopy.
Keeping in mind the pollution problems associated with thermal power plants and vehicular traffic, the role of environmental catalysis cannot be over-emphasised in the Indian context. The inorganic component in environmental catalysis research can deal with the synthesis, evaluation and characterisation of new ceramic and coating materials, as well with the state of active noble metals on such supports.
The role of coordination and organometallic chemistry in solution based catalytic processes i.e. in homogeneous catalysis is now well recognised. There are a large number of very important industrial processes such as asymmetric hydrogenation, isomerisation, oxidation, hydroformylation, carbonylation, hydrocyanation and olefin polymerisation that can be based on homogeneous catalysts.
Basic research in inorganic chemistry related to these technologically important processes would undoubtedly grow at a rapid rate in the coming years. Manufacture of several pharmaceutical intermediates and other find chemicals would increasingly involve use of asymmetric homogeneous catalysis.
Organometallic and cluster Chemistry
Since the discovery of ferrocene and Ziegler-Natta catalysts in the fifties, organometallic chemistry has undergone a spectacular growth in the advanced countries. In India it is part of our significant activities but a much more concerted effort is very desirable. With the help of physical techniques such as multi nuclear NMR and single crystal X-ray diffraction it is possible to show the existence of a fascinating variety of metal-carbon, metal-metal and other metal-nonmetal interactions. Another very attractive feature of organometallic chemistry is its technological relevance to catalysis, chemical vapour deposition techniques, etc.
The areas of molecular cluster chemistry - recent vintage of organometallic chemistry – poses challenging problems to our existing theoretical framework. At what point a group of interacting metal atoms stop behaving like isolated molecules and exhibit the characteristic metallic properties ? Are there rational ways of synthesising such molecules? How do their shapes, chemical re-activities and electronic properties change as the number of metal atoms go up? These are some of the fundamental questions that need to be addressed to. The applications of large clusters as quantum dots (> hundreds of atoms) has been established. It is likely that fundamental studies with metal clusters would provide us fascinating models of heterogeneous catalytic functions. With the available foundation an ambitious and focused activities on organometallic chemistry can be planned (see box)
Bioinorganic chemistry is a fast expanding frontier areas bridging inorganic chemistry and biology. It deals with the role of metal ions in living organisms and addresses to the problems at the interface of inorganic chemistry, biology, agriculture and medicine.
Most metal ions are essential as trace elements for the biological function of living organisms. The metal ions in metalloenzymes occur as natural constituents and perform a very wide variety of specific functions and confer stability associated with life processes. Some of these functions include respiration, photosynthesis, conversion of dinitrogen to ammonia, control of toxicity, catalysis of biochemical reactions, regulation of the synthesis of proteins by cell, conversion of RNA molecules into enzymes, blocking of the onset of genetically inherited disorder and related process.
The structural motifs displayed by the active sites have led to the design of models and model reactions. This will help to understand the structure-function relationship in metalloproteins and enzymes. This area of research is of great interest not only to mimic the biological but also to offer alternative to natural systems.
Inorganic chemistry has made inroads into medicine. Metal complexes are being increasingly used in the treatment of diseases such as cancer, arthritis, hypercalcemia and hypertension. Metal ions have also found use in non-evasive diagnosis. It is challenging to design inorganic compounds which can act more effectively with less toxicity.
Biology offers long range electron transfer and energy migration in short and ultrashort time scales. Often these reactions are mediated through metal centres. The reduction of dioxygen, dinitrogen, carbon dioxide and generation of new molecules constitute important functions of the biosystems. Photochemical energy conversion by green plants and bacteria also involve metal ions.
Metal ions are involved in the catalytic function of the cells through unique ribonucleic acid-based metalloenzyme, called ribozyme. Divalent metal ions such Mg2+, Ca2+ are key to the stability and function of this metalloenzyme. Exploration of variable metal geometry vis-à-vis activity of this metalloenzyme can be important in understanding its function. Several metalloregulatory proteins are also involved in the control of genes involved in metabolism, iron uptake and storage. Metal ions such as Na+, K+, Ca2+ play an important role in signal transduction pathways. These areas of bioinoganic chemistry constitute emerging frontiers of molecular biology.
Diverse functions played by metal ions in biology are influenced by the molecular structure inclusive of ligand environment and not by their redox and ionic states alone. Need for defining the roles of speciation in biology is now becoming evident. The interdisciplinary nature of the fast expanding area of bioinorganic chemistry will need encouragement and support for the interaction of inorganic chemists with scientists in other interface areas.
Theory and Computation
Understanding of inorganic structures and reactivity becomes more meaningful when a good theoretical framework can be designed in tandem with experiments. In turn, theoretical inorganic chemistry is at its best when a correct predictive theory gets applied for addressing a given experimental problem. The innumerable variety that is the hallmark of inorganic chemistry presents diverse questions. Successful applications of theory result from the selection of a theoretical model appropriate for the questions in hand. In addition to the traditional quantum mechanical methods such as the Hartree-Fock, post-Hartree-Fock, and Density Functional theories hybrid methods employing quantum mechanical and empirical force field components for different parts of the same molecule, are becoming popular in study of large metal complexes and enzymes. These are especially important in inorganic molecular modeling. Theoretical study of solids using methodologies extended from all of the above methods will be of crucial importance during the next several years. Studies in inorganic reaction mechanisms and pathways have been rather uncommon and deserve special attention.
Support for theoretical inorganic chemists should come through the availability of easy-access computers, user-friendly programs, internet facilities for remote-access and purchase of copyrighted softwares.
Industrial Applications and Analytical Chemistry
The industry dealing with bulk inorganic chemicals has registered an annual growth of 30% in India during the period between 1989 and 1993. A high growth rate in industrial production of inorganic chemical industry in India is anticipated. However, industrial production systems of many bulk inorganic chemicals are mature and driven by process innovations. On the other hand, many inorganic substances are emerging as performance enhancers in real life systems and these are driven by chemical intuitions.
Importance of inorganic systems in search for new materials and catalysts has added thrust in market driven research in inorganic chemistry in recent years. A higher level of synergy between industry and academy and closer communication between private and public funded research and development need to be emphasised.
Inorganic systems finding speciality applications in cosmetics and sanitation agents and performance enhancement in colour addition, sedimentation, biocidal functions and selective ion binding are growth areas needing chemical intuitions. Materials for ceramics, bulk inorganic drugs, strategic areas, electronic industry, metallurgy and fertilizer applications are gaining wide industrial importance.
With increasing social awareness of industrial pollution and need for waste management, inorganic environmental chemistry has been gaining paramount importance. Trace metal analysis with environmental consequences as well as environmental catalysts with applications in waste management are priority areas. Significant momentum in curiosity driven research in areas with industrial applications in anticipated.
Newer chemical insight into the cleaner processes for bulk inorganic chemicals an speciality inorganics in cosmetic additives, lubricants, sanitation agents, membranes for high temperature applications, colour addition, surface coating, water treatment, selective ion binding, bulk inorganic drugs, electrical and thermal conductivity, surface energy modifiers, catalysts for molecular and regio-selectivity, asymmetric synthesis, precusors for new moleculars based on iron, aluminium, titaniun, zirconium and rare earth and environmental catalysts merit focus.
Application of various infrastructure and sophisticated analytical techniques in pollution monitoring, trace element analysis and speciation and analytical chemistry for imaging of microstructure of inorganic and organic molecules inclusive of surface domains need to be developed.
In order to realise the goals of the plan document outlined above, and to create a vibrant internationally visible, technologically aware inorganic chemistry group in the country, substantial investment needs to be made in establishing an efficient equipment infrastructure.
The importance of an area of research can be attributed to (I) its novelty (ii) challenge the area poses to a clear understanding on the basis of existing laws and paradigms in the discipline (iii) prospect of its immediate usefulness to mankind (iv) irresistible attraction it holds for explorers. In the last category it is difficult to identify any thing. Several new areas of research have been identified in the first three categories and have been considered likely to lead to very fruitful investigations both from academic and applications point of view. Some areas of research are centred around materials and processes, some around creative applications of techniques and yet others are based on known phenomena. Besides there are areas where only theoretical work is possible. They have all been listed below for preferential funding.
Molecular Self assemblies Rationally designed materials
Nanocrystals Biocolloids and emulsions
Molecular clusters Low dimensional solids
Surfactants Electro-chemical sensors
High temperature ceramic material Langmuir-Blodget filsm
Catalysts Drug delivery systems
Gels Fuel cells and secondary batteries
Microporous and mesoporous solids Biopolymers
Layered materials Inorganic magnetic systems
Amorphous and glassy solids Composite films
Solar energy materials Soft solids
NMR relaxation studies
Matrix isolation spectroscopy
Single molecule spectroscopy
Ultrafast reaction dynamics
Oscillatory chemical reactions
Structure and dynamics of large systems
Investigation of soft and illordered solids
The vision paper addresses problems of revitalizing physical chemistry research in the country and assumes that in a reasonable length of time (5-8 years) research level can be raised to international standards. This hope and anticipation will be thwarted unless backed by funds and strategies. It is suggested to DST that the following strategies be adopted so that they lead to high standards of physical chemistry research in the country.
This section intends to prod DST to adopt strategies to make up for lapses elsewhere. The following are the best methods to attract good students to physical chemistry. It is pure wisdom to consider them seriously.