Tuning Photo-functionalization of sp2 Carbon-Hydrogen Bond Inside Water Soluble Supramolecular Nanocage
[FeFe] Hydrogenase H-cluster Biosynthesis
Radical SAM enzymes (1) use a [4Fe-4S] cluster to cleave S-adenosylmethionine to generate the 5’-deoxyadenosyl radical, which in turn abstracts an H-atom from a given rSAM enzyme’s substrate to initiate catalysis. As an example, the RS enzyme HydG lyses tyrosine to generate the CO and CN ligands of the H-cluster of [FeFe] hydrogenase, building an organometallic Fe(CO)2CN(cysteine) moiety that incorporates an iron atom derived from a unique 5-Fe Fe-S cluster (2-7). We have recently characterized the first organometallic intermediate of this catalytic cycle (8) (figure panel). This presentation will focus on the use of EPR spectroscopy to interrogate the geometrical and electronic stuctures of such rSAM enzyme intermediates. Additionally, using HydG along with two other Fe-S maturase enzymes HydE and HydF, we can use cell free synthesis to precisely isotope-edit the H-cluster, which can then be fruitfully probed via EPR spectroscopy targeting its paramagnetic intermediates in the hydrogen oxidation or proton reduction catalytic cycle. New cell free synthesis experiments exploring the effects of deleting subsets of the maturases or adding synthetic analogs in the assembly process are giving new insights into the overall bioassembly of this important metallo-cofactor.
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8.Rao et al., Nat. Chem. (2018) 10:555-560.
Pulse EPR Characterization of the first organometallic intermediate in Fe-Fe hydrogenase bioassembly formed by the radical SAM enzyme HydG (ref 8)
Activity-Based Sensing Approaches to Decipher Transition Metal Signaling
Traditional strategies for development of chemoselective imaging reagents rely on molecular recognition and static lock-and-key binding to achieve high specificity. We are advancing an alternative approach to chemical probe design, termed activity-based sensing (ABS), in which we exploit inherent differences in chemical reactivity as a foundation for distinguishing between chemical analytes that are similar in shape and size within complex biological systems. This presentation will focus on ABS approaches to develop new fluorescent probes for transition metals and reactive oxygen, sulfur, and carbon species and their signal/stress contributions to living systems, along with activity-based proteomics to identify novel targets and pathways that these emerging classes of chemical signals regulate.
Renewable Carbon Engineering Confluence of Modern Biological & Chemical Sciences
World depends heavily on non-renewable fossil products for its energy, materials and chemical needs. Climate trends over past two decades necessitate an aggressive path towards reducing carbon emissions and increasing use of renewable carbon. The total of available renewable carbon is likely to be a combination of first generation (food derived), second generation (non-food derived), third generation (non-land use change) and fourth generation (CO2) carbon. Mankind generates substantial quantities of under-utilized surplus agricultural wastes as also other wastes such as municipal solid wastes, municipal liquid waste and industrial wastes. All these put together have the potential to fully substitute petroleum fuel and materials requirements of the world. Thus there is a need to be able to engineer the available renewable carbon to the products in use today.
Renewable carbon however presents itself in varied and complex forms, and novel science and technology platforms are needed in order to derive desired products from these at reasonable costs. Sustainable and scalable technology platforms are being conceptualised, designed and scaled up at the DBT-ICT Centre for Energy Biosciences using combinations of chemical and biological processes that can convert carbonaceous wastes into products that are today derived from petroleum. The presentation shall broadly discuss these platforms that are likely to have impact on designing sustainable economies.
Probing Ultrafast Chemical Dynamics Inspired by the Rhythms of Fireflies
Coherence phenomena arise from interference, or the addition, of wave-like amplitudes in phase . While coherence has been shown to yield transformative new ways for improving function, advances have been limited to pristine matter, as quantum coherence is considered fragile. Here I will discuss how vibrational and vibronic wavepackets entrain ensembles of molecules, like the synchronized flashing of fireflies. I will discuss how this can be used to probe mechanisms of ultrafast dynamics and how in-step vibrational motion might be employed to control function on ultrafast timescales. I will give examples that include light-harvesting in photosynthesis, energy flow in organometallic molecules that is ‘wired’ by Fermi resonance, and ultrafast electron transfer in molecular systems.
 Scholes, et al. “Optimal Coherence in Chemical and Biophysical Dynamics” Nature 543, 647–656 (2017).
Photodissociation of Acetylacetone: Photoionization and Threshold Photoelectron Spectroscopy Reveal Much More Than OH Radicals
The absorption of light by an organic molecule, and the subsequent pathways for energy transformation and release, are fundamental process governing life on earth. Two of the most important electronic chromophores in organic systems are C=O bonds (carbonyl molecules) and C=C bonds (alkenes and polyenes). Carbonyl molecules, such as acetaldehyde (CH3CHO) also have enol tautomers (H2C=CHOH, vinyl alcohol). This tautomerization converts the weakly absorbing C=O chromophore to a strongly absorbing C=C chromophore. We have studied the photodissociation of acetylacetone (AcAc), which exists at 300 K in the gas phase mostly as the enolone tautomer, rather than the diketo tautomer (see figure). The enolone tautomer is stabilized by both conjugation and an internal hydrogen bond. Previous studies have concluded that OH loss is the dominant (or only) channel when AcAc is excited in the ultraviolet at 266 or 248 nm. However, truly universal detection techniques have not been used in these studies. By combining multiplexed photoionization mass spectrometery (MPIMS), threshold photoelectron photoion coincidence spectroscopy (TPEPICO), and time-resolved infrared absorption spectroscopy of OH radicals, we have discovered that photodissociation of AcAc is much richer than previously presumed, and that OH production is not even energetically allowed following one-photon excitation at 266 or 248 nm. This work demonstrates the power of multiplexed, universal detection of charged particles in photodissociation studies, and lifts the veil on the photodissociation of a molecule that is both an enol and a ketone.
Development of Alkane hydroxylating Biocatalyst using Cytochrome P450 enzyme
Stability and Copper-binding properties of Azurin and its variants probed using optical spectroscopy
Materials Simulation From First-Principles: Fundamental Challenges and Importance of Finite Temperature Modeling
The discovery of the extraordinary activity in catalysis exhibited by small clusters has stimulated considerable research interest. However, in heterogeneous catalysis, materials property changes under operational environment (i.e. at a finite temperature (T) and pressure (p) in an atmosphere of reactive molecules). Therefore, a solid theoretical understanding at a realistic (T, p) is essential in order to address the underlying phenomena.
This talk is, therefore, driven by the vision of computational design of materials at a finite (T, p). Here, I shall introduce a robust methodological approach that integrates various levels of theories combined into one multi-scale simulation to address the environmental effect to predict the properties of materials at a finite T, p. Our approach employs density-functional theory (DFT) combined with ab initio atomistic thermodynamics. In order to quantitatively account the contribution of anharmonic vibrational free energy to the configurational entropy, we have evaluated the excess free energy of selected clusters numerically by thermodynamic integration method with DFT inputs. We further establish the necessity of this finite temperature modeling as DFT (with appropriate exchange and correlation functionals) fails to predict the stable phases even at a moderately low temperature. We have successfully applied our finite temperature modeling approach in various inter-disciplinary fields viz. (i) catalysis[2-3], (ii) defects in semi-conductor, (iii) energy materials[5-6], etc. I shall discuss in details one application of this methodology in addressing (T, p) dependence on the composition, structure, thermodynamic stability of metal hydride clusters in a reactive atmosphere in the context of designing energy materials.
1.S. Bhattacharya, S. Levchenko, L. Ghiringhelli, M. Scheffler Phys. Rev. Lett. 111, 135501 (2013).
2.S. Bhattacharya, D. Berger, K. Reuter, L. Ghiringhelli, S. Levchenko Phys. Rev. Materials (Rapid Commun.) 1, 071601(R) (2017).
3.S. Saini, D. Sarker, P. Basera, S. Levchenko, L. Ghiringhelli, S. Bhattacharya J. Phys. Chem. C 122, 16788 (2018).
4.A. Bhattacharya, S. Bhattacharya Phys. Rev. B 94, 094305 (2016).
5.E. Arora, S. Saini, P. Basera, M. Kumar, A. Singh, S. Bhattacharya J. Phys. Chem. C (article ASAP), DOI: 10.1021/acs.jpcc.8b08687.
6.A. Bhattacharya, S. Bhattacharya J. Phys. Chem. Lett. 6, 3726 (2015).
Computational Design of Nano-clusters by Property-Based Cascade Genetic Algorithms: Tuning the Electronic Properties of (TiO2)n Clusters
For complex open systems such as atomic clusters, defected surfaces, structured over-layers adsorbed on inorganic surfaces, human intuition for predicting relevant structures is likely incomplete or even misleading. Thus, an unbiased algorithm is required for the global optimization. In order to obtain both extensive and accurate sampling of the configurational space - we have developed a massively parallel cascade genetic algorithm (cGA)[1-3]. The term “cascade” refers to a multi-stepped procedure involving increasing levels of accuracy for the evaluation of the globally-optimized quantity (usually total energy of the system). Typically, a cGA starts with classical force field and goes up to density functional theory (DFT) with hybrid functionals. This development has already been applied and successful in various inter-disciplinary fields in materials science[4-6].
Recently, we have extended our cGA-implementation to property based potential energy surface (PES)-scanning to address the famous “inverse problem” of materials science, i.e. how to computationally design materials/structures with the desired electronic properties as opposed to calculating the properties of the given material/structure. In this talk, I shall discuss the fundamental challenges behind this implementation in the context of computational design of cluster-based nano-catalysts.
1.S. Bhattacharya, S. Levchenko, L. Ghiringhelli, M. Scheffler New J. Phys. 16, 123016 (2014).
2.F. Curtis, X. Li, T. Rose, A. Mayagoitia, S. Bhattacharya, L. Ghiringhelli, N. Marom J. Chem. Theory Comput. 14, 2246 (2018).
3.M. Reilly, R. I. Cooper, C. S. Adjiman, S. Bhattacharya et al. Acta Cryst. B 72, 439 (2016).
4.Bhattacharya, S. Bhattacharya J. Phys. Chem. Lett. 6, 3726 (2015).
5.X. Zhao, X. Shao, Y. Fujimori, S. Bhattacharya, L. M. Ghiringhelli, H. Freund, M Sterrer, N. Nilius, S. V. Levchenko J. Phys. Chem. Lett. 6, 1204 (2015).
6.S. Bhattacharya, D. Berger, K. Reuter, L. Ghiringhelli, S. Levchenko Phys. Rev. Materials (Rapid Commun.) 1, 071601(R) (2017).
7.S. Bhattacharya, B. H. Sonin, C. J. Jumonville, L. M. Ghiringhelli, N. Marom Phys. Rev. B (Rapid Commun.) 91, 241115(R) (2015).
Probing Charge Transfer Reaction Coordinate in Supramolecular Donor-Acceptor Frameworks
Enzymes: an Emerging Puzzle of Mechanobiology and Active Matter
The traditional view that enzyme kinetics is only a matter of catalyzing chemical reactions is challenged by recent experiments and theory showing that catalysis enhances enzyme mobility. This is significant to programming spatio-temporal patterns of molecular response to chemical stimulus. This talk will report that the enhanced diffusivity of enzymes is a “run-and-tumble” process analogous to that performed by swimming microorganisms, executed in this situation by molecules that lack the decision-making machinery of microorganisms. One consequence is that enzymes migrate in the direction of lesser reactant concentration when they turn over substrate; they display “anti-chemotaxis.” This run-and-tumble process offers the possible biological function to homogenize product concentration, which could be significant in situations when the reactant concentration varies from spot to spot. Attempts will be made to place these and our related recent findings in the context of larger puzzles in the active matter intellectual community.
About the Speaker:
Steve Granick is a member of the U.S. National Academy of Sciences and American Academy of Arts and Sciences. Among his other major awards are the Paris-Sciences Medal, APS national Polymer Physics Prize, and ACS national Colloid and Surface Chemistry Prize. Holding and having held Honorary and Visiting Positions at multiple universities in Europe and Asia, he has core experience in science globalization.
Structural Biochemistry: A versatile tool to study biological reactions
Structural biochemistry employs structure in conjunction with biochemical and biophysical tools to understand molecular mechanism in biological system. Here, we study two major problems of importance to the Indian scenario; first towards understanding and devising strategies towards combating antibiotic resistance and second in development of biosensors for water quality monitoring. The first problem pertains towards combating the problem of antibiotic resistance. Here, we take a two-fold approach, first, towards discovery of novel enzymes that are divergent between human and pathogens as potential new targets and second focuses on understanding why do pathogens become resistant to existing drugs? Towards the first approach we have selected nucleobase deaminases as model systems to search for alternative therapies. These deaminases are essential enzymes and are structurally very different between humans and bacteria. This difference has already lead them to be used as prodrug-enzyme systems for cancer therapy and now we are exploiting them towards developing therapies for antimicrobial resistance. The problem pertaining to origins of antibiotic resistance involves unearthing molecular mechanisms that promote it. Two prominent systems have been undertaken, the tetracycline efflux pump regulators that activate efflux pumps that deplete antibiotic concentrations in the cells and ribosomal modifying enzymes with focus on methyltransferases that cause a steric clash with certain antibiotics thus result in evading their action. By solving a series of crystal structures of antibiotic efflux pump regulators as well as ribosomal methytransferases with and without DNA and complimenting these studies with biochemical and fluorescence spectroscopy we have delineated strategies to combat antibiotic resistance.
Towards developing biosensors,NtrC transcription regulators that activate sigma 54 class of polymerases and facilitate transcription of stress and virulence combating genes were selected for study. This is because these proteins have a self contained sensor and readout domain on a single polypeptide and thus pose as an efficient sensing-readout system. In this regards the class of sensors that we focused pertain to aromatic xenobiotics like phenol, benzene etc which are prominent pollutants from petroleum, dye and petrochemical industries. The crystal structure of the phenol sensing domain solved by us for this class of enzymes opened the doors towards design of a battery of specific sensors for both phenol as well as benzene group of compounds. The detection of these compounds was further optimized to low ppb levels and the shelf life, stability and sensitivity optimized to yield sensors that are potentially compatible in a commercial setting. Their xenobiotic sensing potential was further exploited by employing a combination of structure based design as well as mutagenesis created biosensors for not only phenol but xyenols, benzene derivatives and other aromatic pollutants. The sensor design has been translated to a chip based design where, the protein has been immobilized onto mesoporous silica nanoparticles. The aim is to create cheap and effective biosensor units that can detect these pollutants insitu.
Quantum Dot Antennae for Photovoltaics
The low-cost third-generation photovoltaic devices with semiconductor quantum dot (QD) absorbers are becoming popular due to the QDs having band gap tunability, high absorption coefficient, solution processability, multiple exciton generation and stability.1-8 Nonetheless owing to the inherent drawback of abundant surface trap states in QDs, the propensity of interfacial charge recombination have always limited their power conversion efficiencies (PCE). In spite of such challenges, QD sensitized solar cells (QDSSCs) have emerged as the newest technology in the NREL chart and CsPbI3 happen to be the new QD leader in 2017 with PCE of 13.4%. This lecture at first will discuss our efforts to improve the photoanode performance of liquid junction QDSSCs with core-shell II-VI and I-III-VI QD absorbers,4-6 along with the counter electrode strategies.7 The second part of this lecture will deal with few of our approaches to fabricate relatively stable all-inorganic lead perovskite QD sensitized solar cells.9,10 Our approach has been validated by transient absorption spectroscopy which shows lesser abundance of trap states and enhanced charge carrier recombination lifetime.
(1) Halder, G.; Ghosh, D.; Ali, Md. Y.; Sahasrabudhe, A.; Bhattacharyya, S. Langmuir 2018, 34, 10197-10216. (Invited Feature Article)
(2) Ghosh, D.; Halder, G.; Sahasrabudhe, A.; Bhattacharyya, S. Nanoscale 2016, 8, 10632-10641.
(3) Sahasrabudhe, A.; Kapri, S.; Bhattacharyya, S. Carbon 2016, 107, 395-404.
(4) Sahasrabudhe, A.; Bhattacharyya, S. Chem. Mater. 2015, 27, 4848-4859.
(5) Halder, G.; Bhattacharyya, S. J. Mater. Chem. A 2017, 5, 11746-11755.
(6) Halder, G.; Ghosh, A.; Parvin, S.; Bhattacharyya, S. Chem. Mater. 2018, DOI: 10.1021/acs.chemmater.8b03743.
(7) Ghosh, D.; Ghosh, A.; Ali, Md. Y.; Bhattacharyya, S. Chem. Mater. 2018, 30, 6071-6081.
(8) Halder, G.; Bhattacharyya, S. J. Phys. Chem. C 2015, 119, 13404-13412.
(9) Ghosh, D.; Ali, Md. Y.; Chaudhary, D. K.; Bhattacharyya, S. Sol. Energy Mater. Sol. Cells 2018, 185, 28-35.
(10) Unpublished results.