Rational Design of Functional Materials: A Chemist's Approach
Functional materials have assumed prominent position in several high tech areas. Such materials are not classified on the basis of their origin, nature of bonding or processing techniques but are classified on the basis of functions which they can perform. The synthesis of such materials has been a challenge and also opportunity to chemists. New functional materials can be designed by interplay of synthesis and crystallographic structure. Other approaches for design of these materials are defects engineering and concepts of hybrids. Unconventional synthetic routes play an important role in this direction as many of these new materials are metastable and hence it is not possible to prepare them by conventional solid state synthesis. We have prepared [1-18] a number of new functional materials guided by crystallographic approach coupled with novel synthesis protocols. Some typical materials which will be discussed in this talk are La1-xCexCrO3 (materials with tunable band gap and magnetic properties), CeScO3 (with unusual reversible conversion to fluorite lattice), Gd1-xYxInO3, GdSc1-xInxO3, YIn1-xFexO3 (tunable dielectrics) and several lead free relaxor materials. Perovskite and fluorite-type materials with trivalent Ce3+ were successfully prepared from suitable precursor powders by a controlled heating under low pO2. Several interesting pyrochlore based oxygen storage materials, viz. Ce2Zr2O7+x (x = 0.0 to 1.0), Gd2-xCexZr2O7 andGd2-xCexZr2-xAlxO7 (x = 0.0 to 2.0) have been prepared, which have shown interesting redox catalysis. The simple concepts like rA/rB ratio of A2B2O7 pyrochlores could be used to tailor the functional properties. The major focus of this talk will be on the role of synthesis, novel properties exhibited by these functional materials, and their crystallographic correlation.
Our recent publications in the field functional materials
 Chem. Mater. 21 (2009) 125
 J. Phys. Chem. C 113 (2009) 12663
 Inorg. Chem. 48 (2009) 11691
 Inorg. Chem. 49 (2010) 10415
 Inorg. Chem 49 (2010) 1152
 Chem.- A Eur. J.17 (2011) 12310
 Chem. Mater. 24 (2012) 2186
 Analysts 137 (2012) 760
 Nano Letters 12 (2012) 3025
 J. Phys. Chem C 117 (2013) 10929
 J. Phys. Chem. C 117 (2013) 2382
 Inorg. Chem. 52 (2013) 7873
 Inorg. Chem. 52 (2013) 13179
 J. Mater. Chem. C, 1 (2013) 3710
 J. Phys. Chem. C 118 (2014) 20819
 Inorg. Chem. 53 (2014) 10101
 Dalton Transaction 44 (2015) 10628
Teaching Sponges New Tricks: Redox Reactivity and Charge Transport in Microporous Metal-Organic Frameworks
Traditional applications of metal-organic frameworks (MOFs) are focused on gas storage and separation, which take advantage of the inherent porosity and high surface area of these materials. The MOFs’ use in technologies that require charge transport have lagged behind, however, because MOFs are poor conductors of electricity. We show that design principles honed from decades of previous research in molecular conductors can be employed to produce MOFs with remarkable charge mobility and conductivity values that rival or surpass those of common organic semiconductors and even graphite. We expect that such high surface area, ordered, and crystalline conductors will be used for a variety of applications in thermoelectrics, energy storage, electrocatalysis, electrochromics, or new types of photovoltaics. Another virtually untapped area of MOF chemistry is related to their potential to mediate redox reactivity through their metal nodes. We show that MOFs can be thought of as unique macromolecular ligands that give rise to unusual molecular clusters where small molecules can react in a matrix-like environment, akin to the metal binding pockets of metalloproteins. By employing a mild, highly modular synthetic method and a suite of spectroscopic techniques, we show that redox reactivity at MOF nodes can lead to the isolation and characterization of highly unstable intermediates relevant to biological and industrial catalysis, and to unusual reactivity patterns for small molecules.
The W(Hole) Story of β-barrel Pore-forming Toxin Vibrio cholerae Cytolysin
Bacterial β-barrel pore-forming toxins (β-PFTs) constitute a unique class of membrane-damaging cytolytic proteins.β-PFTs are, in general, produced by the pathogenic bacteria as water-soluble monomeric molecules. In contact with their target eukaryotic cells, they assemble into transmembrane oligomeric β-barrel pores, thus destroying the natural permeability barrier function of the target cell membranes. Vibrio cholerae cytolysin (VCC) is a prominent member in the β-PFT family. It is produced by most of the pathogenic strains of V. cholerae, the causal organism of the severe diarrheal disease cholera.VCC is shown to evoke critical cytotoxic effects in wide array of host eukaryotic cells, and therefore, it is considered as a potent virulence factor of V. cholerae. High-resolution three-dimensional structures are known for both the water-soluble monomeric form as well as the oligomeric pore state of VCC. However, mechanistic details of the membrane pore formation process employed by the toxin remain only partly described.One of our major research interests is focused toward elucidating the detail structure-function mechanisms associated with the b-barrel membrane pore formation process of VCC. In my talk, I will present some of our recent studies that have provided new insights regarding the mechanism of action of VCC, in the context of the generalized β-PFT mode of actions.
Structures and Dynamics using two-dimensional infrared and sum frequency generation spectroscopies
Two dimensional infrared (2D IR) spectroscopy, which is the infrared analog of 2D NMR, has the ability to resolve congested spectra better than linear infrared spectroscopy by adding an extra dimension. When multiple vibrational modes are present in the system of interest, the 2D IR spectrum depends critically on whether these modes are coupled to one another. One of the major strengths of 2D IR over conventional linear IR is that coupling between different modes is probed directly, and existence of cross-peaks in a 2D IR spectrum is evidence for coupling between different vibrations. In the event that there are chemically distinct species present in equilibrium, wherein fast chemical processes like hydrogen bond making and breaking interchange populations between the species, cross peaks appear on the time scales of the equilibrium kinetics of this chemical exchange. Examples of such exchange dynamics, observed for aromatic nitriles in methanol will be presented. Similar interpretations can be applied to the ultrafast dynamics of liquids, which can be thought of as a distribution of well-defined structures characterized by different solvation environments evolving spectrally on a range of time scales. Hence, the spectral diffusion seen in 2D IR experiments that derives from decay of the vibrational frequency correlations might be thought of as exchange among multiple solvent−solute configurations, and these underlying configurations are resolvable when the solvent dynamics are significantly slower than bulk. 2D IR spectra of amide vibrations in proteins and peptides exhibit solvent exchange under certain conditions, thus verifying the above hypothesis, and examples of the same will be discussed. The capabilities of 2D spectroscopy can be extended to surfaces through two-dimensional sum frequency generation (2D SFG) spectroscopy, which is a novel technique capable of measuring spectra analogous to 2D IR but with monolayer sensitivity and SFG selection rules. Applications of 2D SFG to exploring structures of a peptide segment FGAIL, a conserved sequence found in the islet amyloid polypeptide, will be presented. The 2D SFG spectra of FGAIL on model membranes reveal how hydrogen bonding interactions can play a vital role in the formation of aggregates on membranes, which is at the heart of understanding amyloid diseases such as type II diabetes. New technological advances that implement multi beam detection schemes in 2D IR experiments using mid-IR focal plane arrays will be shown. Details of future research plans will also be presented.
Vibrational dynamics in proteins using two-dimensional infrared spectroscopy
The time course of a vibrational probe is ultra-sensitive to the motions of nearby atoms, particularly those with net charges like water, which cause instantaneous fluctuations of the vibrational frequency. Two dimensional infrared spectroscopy (2D IR) leads to direct quantitative inferences on these motions. Over the past decade, 2D IR spectroscopy has developed into a promising method for probing site-specific structure and dynamics of peptides, proteins and other biological assemblies. The principles of 2D IR spectroscopy and approaches for extracting the vibrational frequency correlation function from 2D spectra will be discussed. The application of 2D IR methodologies, employed to investigate the pH induced ebb and flow of water in the M2 proton channel in influenza viruses through the spectral dynamics of the backbone amide modes, will be presented. The 2D IR spectroscopy of pore lining amides in the M2 channel reveal that the conformational equilibrium in M2 entails a change in the mobility of the channel water similar to what might be expected for phase transition from frozen to liquid water. This approach was extended to address drug binding modes in the channel. 2D IR experiments with drug-free and drug-bound channels expose water mobility in the channel under different drug binding conditions, which is reflected in the spectral dynamics of the Ala30 and Gly34 amides. The results suggest a favorable entropic factor for drug binding owing to disruption of water structures, thus revealing a functional model of drug binding in the channel that is in qualitative consistency with the model proposed from MD simulations. The unique capabilities of Fourier transform infrared spectroscopy can be utilized for imaging applications, and a new table-top technique for collecting wide-field Fourier transform infrared (FTIR) microscopic images by combining a femtosecond pulse shaper with a mid-IR focal plane array will be presented. Infrared absorption images were collected for a mixture of W(CO)6 or Mn2(CO)10 absorbed polystyrene beads, demonstrating that this technique can spatially resolve chemically distinct species. Extension of this method to hyperspectral 2D IR microscopy will also be discussed.
Domino Strategies for Syntheses of Natural Products and New Molecular Scaffolds
Domino and multicomponent reactions are always attractive and they are expected to provide the target molecules efficiently in a shortest possible route. Our group has been engaged in designing simple and efficient domino strategies for the syntheses of biologically active natural products and natural product like molecules. In this lecture, our efforts leading to syntheses of vinigrol, cyclic guanidines and N-heterocyclic amides will be discussed in details.
Vinigrol,1 a unique diterpene containing the decahydro-1,5-butanonaphthalene carbon skeleton was shown to exhibit a broad spectrum of biological activity. Besides the multiple sites of oxygenation, vinigrol contains a tricyclic core having a cis-fused [4.4.0] system bridged by an eight-membered ring and eight contiguous stereocenters. We recently reported2 an enantioselective formal synthesis of vinigrol involving a1-2-3 strategy: one pot and 2-reactions with the formation of3-rings leading to the core structure of vinigrol from its stereochemically well-defined acyclic precursor.
The cyclic guanidines3 and N-heterocyclic amides4 are important structural units present in biologically active drug molecules. However, the existing methods suffer from harsh conditions, narrow functional group tolerance, poor atom economy, low yielding and so; it warrants an efficient protocol for their syntheses. We have developed a one-pot Cu-catalyzed cascade routes to these unique cyclic guanidines and N-heterocyclic amides5 from readily available starting materials.
1. Uchida, I.; Ando, T.; Fukami, N.; Yoshida, K.; Hashimoto, M.; Tada, T.; Koda, S.; Morimoto, Y.J. Org. Chem. 1987, 52, 5292–5293.
2. Betkekar, V. V.; Sayyad, A. A.; Kaliappan, K. P.Org. Lett.2014,16, 5540-5543.
3. Subramanian, P.; Kaliappan, K. P. Eur. J. Org. Chem. 2014, 5986–5997.
4. Hou, H.; Wei, Y.; Song, Y.; Mi, L.; Tang, M.; Li, L.; Fan, Y. Angew. Chem. Int. Ed. 2005, 44, 6067-6074.
5. Subramanian, P.; Indu, S.; Kaliappan, K. P. Org. Lett.2014,16, 6212-6215.
Musings with Intermolecular Interactions
In general intermolecular interactions between pair of closed shell molecules can be represented by [-1, -6, +12] potential. Various intermolecular interaction varies significantly due to the differences in the weightage for each of the three terms. Spectroscopy and computational chemistry provide the reasonable understanding of many intermolecular interactions. However, each method has specific shortfalls. Physically meaningful models can only be constructed by adequately addressing these shortfalls while interpreting the data. The importance of each of the components of [-1, -6, +12] potential in understating hydrogen bonding, π-π stacking and in foldamers will be highlighted
Accelerating virtual discoveries by augmenting quantum mechanics with
Acceleration of socio-economically important researches such as the design of catalysts, drugs, or conducting materials, lies in reliable virtual screening to identify candidate molecules or materials with desired properties. Any attempt to address this problem exclusively via brute force high-throughput computation is doomed to fail due to the combinatorial hardness of the problem, and the limitations of the compute power that is available on the planet. In my talk, I will highlight some out-of-the-box approaches to navigate chemical space with a focus on the application of supervised machine-learning combined with legacy quantum chemistry methods such as even semi-empirical models. This strategy has very recently been shown to reach desirable quantum chemical accuracy, for forecasting a multitude of properties, ranging from thermochemistry to NMR chemical shifts, even for new molecules which had no part in
training. I will present an overview of this emerging sub-discipline of theoretical chemistry, and discuss some of the prominent contributions in this venue.
 Snyder, et al., Finding density functionals with machine learning, Physical Review Letters, 108 (2012) 253002.
 Ramakrishnan, et al., Big data meets quantum chemistry approximations: The ∆-
machine learning approach, Journal of Chemical Theory and Computation, 11 (2015)
 Ghiringhelli, et al., Big data of materials science: Critical role of the descriptor, Physical Review Letters, 114 (2015) 105503.
 Special Issue: Machine learning and quantum mechanics, International Journal of Quantum Chemistry, 115 (August 2015).
Rapid and accurate simulation of electron dynamics across nanostructures
Accurate first-principles modeling of electron dynamics is a challenging area of research. To follow the dynamics of molecular electron density one has to solve the time-dependent electronic Schrödinger equation (TDSE). Straight-forward extensions of common quantum chemistry methods to the time-dependent domain reveal density functional theory (DFT), or even the coupled cluster theories to be extremely unsuited for this purpose. In a series of studies, we have demonstrated linear equations of motions to be one of the fundamental requirements to reliably model electonic wavepacket dynamics, or coherent controlled state-to-state excitation. To this end, we have developed one of the most effcient implementations of the time-dependent configuration-interaction (TDCI) methodology to solve the TDSE. Our
implementation has been successfully applied to follow the electron transport across molecular wires and nanostructures terminating in a small metal cluster or a model gold surface. When combined with imaginary time propagation, or other variational schemes TDCI can be utilized also to perform time-independent task of computing the bound states. The present talk will provide an overview of the TDCI methodology and summarize the results of some recent applications.
 Raghunathan, et al., Critical examination of explicitly time-dependent density functional theory for coherent control of dipole switching Journal of Chemical Theory and Computation, 7 (2011) 2492.
 Ulusoy, et al., The multi-configuration electron-nuclear dynamics method applied to LiH, The Journal of chemical physics, 136 (2012) 054112.
 Ramakrishnan, et al., Control and analysis of single-determinant electron dynamics,
Physics Review A, 85 (2012) 054501.
 Ramakrishnan, et al., Electron dynamics across molecular wires: A time-dependent configuration interaction study, Chemical Physics, 420 (2013) 44.
 Ramakrishnan, et al., Charge transfer dynamics from adsorbates to surfaces with single active electron and configuration interaction based approaches, Chemical Physics, 446 (2015) 24.
Towards Understanding Natural and Artificial Light Harvesting – New Theoretical Insights and Optical Techniques
With substantial budget hikes towards renewable energy technologies, all the leading and developing world economies are recognizing the need to reduce their dependence on fossil fuels. Understanding the fundamental physics of light-harvesting in both natural and artificial systems is the key to development of efficient light-harvesting technologies. I will be presenting my thesis work on the following topics: i) The non-adiabatic energy funnel (Tiwari et al. PNAS 2013) underlying the remarkably efficient electronic energy transfer in natural light harvesting antennas. Future experiments to further investigate this new mechanism will also be discussed. ii) A novel femtosecond time-resolved photonumeric technique to quantitatively characterize transient chemical species. Preliminary measurements on PbSe quantum dots relevant for third generation photovoltaic technologies will also be presented.This talk will mainly focus on the first topicwhile briefly touching the key ideas of the second topic.
Probing Plant Metabolism and Bio-molecular Interaction: Studies by NMR
Synthesis of oxa- and aza-cycles is a topic of contemporary interest owing to the presence of these moieties in structurally challenging and biologically important natural products. Our group is involved in developing strategies for their synthesis using vinylogous carbonates and carbamates under radical as well as non-radical conditions. In this regard, we have developed a highly stereoselective synthesis of new oxa-cages and angular oxa-triquinanesvia alkyl radical cyclisation to vinylogous carbonates. To expand the scope of vinylogous carbonates and carbamates in non-radical pathways, a highly diastereoselective method for the synthesis of cyclopropafuranones and cyclopropapyrrolidinones from vinylogous carbonates and carbamates, respectively, has been established. These donor-acceptor substituted cyclopropanes (DACs) have been converted into diversely functionalized THFs, THPs, lactones, pyrrolidine, piperidine and lactam derivatives by regioselective ring opening of the cyclopropane ring. An efficient strategy for the synthesis of THF, THP and oxepane derivatives has been developed employing a tandem SN2-Michael addition to vinylogous carbonates. Further, we have shown that the intramolecular Pictet-Spengler type cyclization of the indole moiety to the vinylogous carbonates under Lewis acidic conditions can be effected leading to N-fused oxazino indoles. We have demonstrated that Lewis acid mediated reductive etherification can be used for gaining stereoselective access to diverse array of 1,4-heterocycles like morpholines, which are important pharmacophores. Very recently, we have developed divergent synthesis of N-fused indolylidine, indole, and indoline derivatives using alkyne iminium ion cyclization. The talk will highlight some of thesestudies for the stereoselective construction of bioactive oxa- and aza-cycles.
References:(a) Gharpure, S. J.; Shukla, M. K.; Vijayasree, U. Org. Lett.2009, 10, 5466. (b) Gharpure, S. J.; Sathiyanarayanan, A. M. Chem. Commun.2011, 47, 3625. (c) Gharpure, S. J.; Prasad, J. V. K.J. Org. Chem.2011, 76, 10325.(d) Gharpure, S. J.; Vijayasree, U.; Reddy, S. R. B.Org. Biomol. Chem., 2012, 10, 1735. (e) Gharpure, S. J.; Prasad, J. V. K. Eur. J. Org. Chem. 2013, 2076. (f) Gharpure, S. J.; Prasath, V. Org. Biomol. Chem., 2014, 12, 7397. (g) Gharpure, S. J.; Nanda, L. N.; Shukla, M. K. Org. Lett.2014, 16, 6424. (h)Gharpure, S. J.; Anuradha, D.; Prasad, J. V. K.; Rao, P. S.Eur. J. Org. Chem. 2015, 86. (i) Gharpure, S. J.; Shelke, Y. G.; Kumar, D. P. Org. Lett.2015, 17, 1926.
Purpose-built Molecules & Molecular Assemblies for Predictive Optical Responses
Designing molecules or molecular assemblies that are capable of functioning in predictive manner in presence of a certain external stimulation is an area that has fascinated most chemists since long. The rich database on various synthons for non-bonding interactions as well as synthetic intricacies in making organic/inorganic molecules has provided means for achieving molecular assembly or function in a desired fashion. Our research interests include harnessing both coordinative interactions as well as various non-bonding interactions for realizing desired functions of a molecule or molecular assembly.
Over the recent years, dye-sensitized solar cells (DSSC) have emerged as the major cost effective alternative for efficient harvesting of solar power. However, conversion efficiency of these DSSCs is still lower than that of the silicon-based photovoltaic cells. Among various factors, nature of the anchoring group and thus the synthesis of purpose-built sensitizer molecule contribute significantly in designing an efficient dye. Our sustained efforts on this aspect shall be discussed to reveal the relationship between the design aspects, dynamics of the photoinduced processes and the mechanistic elucidation for explaining the possible efficiency of the DSSC.
We could also demonstrate that changes in molecular conformation or motions in a supramolecular assembly could actually be probed by monitoring changes in optical responses in an appropriately designed host-guest assembly and such examples are scanty in contemporary literature. Some of our recent efforts on this issue shall also be discussed in the presentation.
Small Molecule Tools for Studying Cellular Redox Homeostasis
It has long been recognized that maintenance of redox homeostasis is crucial for cellular survival and growth. However, precise cellular responses to redox stress, where cells loses capacity to counteract excess of reducing or oxidizing equivalents, remain poorly characterized. An important sub-set of various cellular components useful for maintenance of redox homeostasis is gaseous reactive species of nitrogen, oxygen and sulfur. Altered levels of these gases are associated with various pathophysiological conditions and disease states underscoring the importance of regulating intracellular levels of these species. Owing to their high reactivity and diffusible nature, the use of chemical tools for this purpose has become indispensable. Our laboratory has developed several small molecule tools to reliably enhance gaseous redox-active reactive species including superoxide (O2·), nitric oxide (NO), sulfur dioxide (SO2) and hydrogen sulfide (H2S). Our design strategy offers both scope for spatiotemporal control as well as cell-type specificity. Here, we present examples of tools developed in our laboratory that can reliably enhance reactive oxygen, nitrogen and sulfur species and the progress towards studying cellular responses. For example, we have developed bis(4-nitrobenzyl)sulfane, a class of organic sources of H2S, that is specifically activated by the bacterial enzyme nitroreductase to generate H2S. We provide evidence for the suitability of (4-nitrobenzyl)sulfanes for enhancement of intracellular H2S levels in a range of bacteria including mycobacteria. Next, we have developed HyPR-1, a small molecule containing a superoxide generator, strategically linked to a diazeniumdiolate-based nitric oxide donor. HyPR-1 produces nearly temporally concurrent fluxes of superoxide and NO in physiological pH when triggered by DT-diaphorase (DT-D), an enzyme that is commonly found in mammalian cells. We provide unequivocal evidence for HyPR-1’s ability to generate ONOO in cell-free systems in the presence of DT-D as well as reliably enhance ONOO within cells. Using HyPR-1 in colorectal cancer cells as a case study, we present evidence that ONOO mediates epithelial-mesenchymal transition (EMT), which is a key process in metastasis and tumour progression. Together, these studies lay the foundation for understanding mechanisms of antibiotic resistance and cancer progression and metastasis.
Protein Conformation, Dynamics and Aggregation: One Molecule at a time
Our laboratory has been investigating the mechanistic details of how a protein attains its functional three dimensional structure. We are also studying the conformational and other factors which contribute to the alteration of folding pathways leading to aggregation. The problems of protein mis-folding and aggregation, which have serious implications in a number of neurodegenerative diseases, are difficult to study. This is because; the folding and aggregation landscape is inherently heterogeneous, consisting of multiple pathways. Since the traditional biochemical and biophysical techniques require an optimum concentration of aggregated molecules for their detection, monitoring the early stages is difficult. Our lab has been using sensitive fluorescence methods, which can provide single molecule resolution, to address these problems. In this talk, we would discuss some of these data, which have been obtained using a number of relevant model proteins.