TIFR
Department of Chemical Sciences
School of Natural Sciences

Calender

October 14, 2019 at 4.00 pm in AG-69

Title :

The Electron Attachment Induced Radiation Damage to Genetic Materials : The Role of Water

Abstract :

Radiation damage to genetic material is one of the active fields of chemical research with implications in both the cause and cure of cancer.  The origin of the damage for a long time is attributed to ionization and excitation process created by the high energy radiation.  But recent experiments have highlighted the critical role played by the low-energy secondary electron in the radiation damage process[1]. Water has been shown to accelerate the process of radiation damage[2]. We have proposed a mechanism for the water-mediated attachment of electron to nucleobases. The initial electron attached state is localized on the water, and the water bound states act as a doorway for the electron attachment to nucleobases. Subsequently, the electron is transferred  to the nucleobase due to the mixing of the electronic and the nuclear degrees of  freedom in the solvated nucleobase. Our theoretical simulations show that the presence of bulk water increases the rate of the electron transfer, which takes place in the ultrafast time scale. The local structure of water around the nucleobase anion plays a crucial role in the electron attachment process. The computed adiabatic electron affinity of nucleobases and rate of electron transfer from water to the nucleobases shows good agreement with the experimental results validating our proposed mechanism[3].

 

         

References:

[1]B. Boudaïffa, P. Cloutier, D. Hunting, M. A. Huels, L. Sanche, Science (80. )., 2000, DOI:10.1126/science.287.5458.1658.

[2]J. Ma, F. Wang, S. A. Denisov, A. Adhikary, M. Mostafavi, Sci. Adv., 2017, DOI:10.1126/sciadv.1701669.

 [3]      M. Mukherjee, D. Tripathi, A.K. Dutta, 2019 (to be communicated )

 

 

 

September 19, 2019 at 4.00 pm in AG-80

Title :

Cu2ZnSnS4: A potential photovoltaic material for low-cost thin film solar cell

Abstract :

Shifting to renewable energy is the solution for meeting the ever-increasing energy demand as well as preventing the deterioration of the environment due to the use of fossil fuel-based energy sources. The Sun from which abundant energy is received on the Earth is probably the most promising renewable energy source. A solar photovoltaic (PV) device converts the solar radiation directly into electricity. Such as device is comprised of a photo-absorber material that absorbs incident photons and uses their energy for raising the chemical potential of electrons within the material. Other materials interfaced with this photo-absorber help collect these excited electrons at one end of the PV device and thereby help generate a potential difference.

Silicon has been the semiconductor of choice for the role of photo-absorber in a PV device, however, due to lower absorption coefficient (α =103 cm−1; λ < 825 nm) and brittleness, several other materials and related PV technologies have been developed. Among these, the technologies based on CdTe and Cu(In,Ga)Se2 (CIGSe) semiconductors have been commercially successful with a photoconversion efficiency  of more than 20 %. However, the concerns associated with toxic element Cd and less abundant elements In and Ga have propelled the investigation for alternative semiconductors. A quaternary compound Cu2ZnSnS4 (CZTS) is a promising candidate owing to the facts that all the elements used in it are non-toxic and have relatively abundant availability; moreover, it has a high absorption coefficient (α =104 cm−1; λ < 825 nm) and close to an optimum band gap ( = 1.5 eV).

In the present talk, the challenges associated with the synthesis of CZTS thin films via solution chemistry will be discussed and ways to eliminate/control them have been suggested. First, in order to obtain a film with a desired surface morphology, a combined use of the chloride and acetate salts of copper in the precursor solution has been found to be helpful. Further to this, a capping layer of ZnS was necessary on top of the precursor film in order to obtain a CZTS thin film with controlled surface morphology. The CZTS film prepared by this strategy had a stoichiometric composition, the grain size of the order of ~ 200 nm,  = 1.5 eV, and a high hole-carrier density ~ 1019 cm−3.

Further, the tuning of electrical and optical properties of the CZTS via incorporation of silver (Ag) at copper sub-lattice sites in CZTS will be discussed. Thin films of the resulting pentanary alloys (Ag1-xCux)2ZnSnS4 (0 ≤ x ≤ 1) show a remarkable change in their microstructure and electronic properties with increasing Ag content. Going from Cu2ZnSnS4 (x = 0) to Ag2ZnSnS4 (x = 1), the grain size increased from 0.2 to 2 μm which has been correlated to the formation of intermediate phase with relatively lower melting point. 

Finally, optimized (Ag1-xCux)2ZnSnS­4 thin films were incorporated in a PV device that resulted in a short circuit current density Jsc of 9.47 mA/cm2, open circuit voltage (Voc) of 600 mV, and a fill factor of 34 % leading to ƞ of 1.92 %. 

September 13, 2019 at 11.30 am in AG-80

Title :

Targeted Prodrugs to Manipulate Copper Biology of Prostate Cancer

Abstract :

Cancer cells have considerably different metallome than normal cells. Especially prostate cancer has been shown to overexpress several important copper trafficking proteins and recruit high levels of copper, making it more sensitive towards drugs like disulfiram.1 Disulfiram acts by altering the copper biology of prostate cancer. Though disulfiram is a promising anticancer agent, the off-target activities lead to adverse side effects.2 Disulfiram’s off-target effects can be mitigated in the cancer setting by chemical modification of the active pharmacophore, dithiocarbamate, in ways that target it preferentially to prostate cancer cells.3 In this seminar, I will present the design, development, and activity of dithiocarbamate prodrug, a Cu prochelator, that is activated in the prostate cancer microenvironment specifically.

 

References :

 

(1)      Safi, R.; Nelson, E. R.; Chitneni, S. K.; Franz, K. J.; George, D. J.; Zalutsky, M. R.; McDonnell, D. P. Copper signaling axis as a target for prostate cancer therapeutics.Cancer Res 2014, 74, 5819.

(2)      Schweizer, M. T.; Lin, J.; Blackford, A.; Bardia, A.; King, S.; Armstrong, A. J.; Rudek, M. A.; Yegnasubramanian, S.; Carducci, M. A. Pharmacodynamic study of disulfiram in men with non-metastatic recurrent prostate cancer.Prostate Cancer Prostatic Dis 2013, 16, 357.

(3)      Bakthavatsalam, S.; Sleeper, M. L.; Dharani, A.; George, D. J.; Zhang, T.; Franz, K. J. Leveraging γ-Glutamyl Transferase To Direct Cytotoxicity of Copper Dithiocarbamates against Prostate Cancer Cells.Angew. Chem. Int. Ed. 2018, 57, 12780.

September 11, 2019 at 11.30 am in AG-80

Title :

Bispidine coordination chemistry – ligands for medicinal chemistry, bioinorganic modeling and oxidation catalysis

Abstract :

All important properties of coordination compounds – hermodynamics (complex stabilities, metal ion selectivities, redox potentials), kinetics (reaction rates, selectivities and pathways) as well as electronics (spectroscopy and magnetism) – depend on their structure. The structure of metal complexes is the result of metal ion and ligand preferences, and it is shown that ligand preferences prevail, especially with ligands as rigid as the bispidines. The unique geometries of bispidine transition metal and lanthanide complexes will be described and the resulting properties will be discussed. Specific examples and applications that will be presented include the CuII/I couple with applications ranging from oxygen activation, azidirination and positron emission tomography (PET) and high-valent nonheme iron model chemistry (oxidation catalysis).
 
References
P. Comba, M. Kerscher, W. Schiek Progr. Inorg. Chem., 2007, 55, 613.
P. Comba, M. Kerscher, K. Rück, M. Starke Dalton Perspective 2018, 47, 9202

August 29, 2019 at 2.30 pm in AG-80

Title :

Engineering Artificial Metalloenzyme for Enantioselective Catalysis

Abstract :

Artificial metalloenzymes (ArMs) offer new opportunities to improve catalytic selectivity and efficiency. They are a class of catalysts that result from incorporation of an organometallic catalyst precursor within a host protein. This combination exploits the reactivity of the transition metal catalysts while taking advantage of the selectivity and adaptability of proteins. Our research has demonstrated formation of ArMs through strain promoted azide-alkyne cycloaddition. It is a ‘click’ bioconjugation approach, where a covalent link is formed between metal complex and protein through cycloaddition of a strained alkyne linker and genetically encoded p-azidophenyl alanine on the protein scaffold. Several scaffold proteins and cofactor components were explored to demonstrate versatility of this method. Extensive biophysical characterization of these Arms was also done by mass spectrophotometry, fluorescence spectroscopy and X-ray crystallography. Scaffold proteins were engineered to get accelerated bioconjugation of metal cofactors without perturbing the structural conformation around the catalytic site. Enantioselective carbene insertion into Si-H bond and olefin has been observed using dirhodium based ArMs. Further improvement in selectivity was explored via structure based single point mutagenesis and directed protein evolution approach.

August 26, 2019 at 4.00 pm in AG-69

Title :

Series “Quantum” Resistors: Design of “molecule like” spin-filtering using superlattices

Abstract :

In the 1980s, the era of mesoscopic transport while clearing many mists about the microscopic nature of electrical resistance, simultaneously unveiled new and counter-intuitive aspects about it. An example being that of double barrier tunneling and its hallmark consequence - two “quantum” resistors in series may give rise to an equivalent resistance that is smaller than that of each component! This aspect has been extensively studied in the context of microelectronic applications of resonant tunneling diodes (RTD). In this talk, while keeping the motif of “multiple quantum resistors”, we draw attention to some next generation applications in the realm of spintronics and energy conversion-an area commonly referred to as spin-caloritronics.

Starting from the basic tenets of quantum transport in the double barrier context, we present novel double barrier applications in spintronics based on the physics of resonant spin filtering [1-3]. We demonstrate an ultraenhancement in the tunnel magneto resistance (TMR), well in excess of 2000%, as a result of highly sensitive and tunable spin filtering physics. With myriad applications possible by utilizing such a tunable spin filtering scheme [1- 3], we present device designs catered toward emerging logic, memory and sensing functionalities that include (i) ultra-high sensitivity magneto resistance H-field sensors (ii) Improved spin transfer torque switching resulting from the non-trivial spin current profiles, and (iii) high-power output microwave generators and oscillators based on resonant spin-transfer torque dynamics.

We then extend our analysis on how electronic analogs of optical phenomena such as anti-reflection coatings and Fabry-Perot resonances may be used to engineer double barrier tunneling for spintronic and thermoelectric power co-generation [4-6]. These ideas, we believe would be useful in the next generation of spintronic logic-memories that combine in-chip heat to spin current co-harvesting.

 References :

[1] N. Chatterji, A. A. Tulapurkar and B. Muralidharan, Appl. Phys. Lett., 105, 232410,(2014).

[2] A. Sharma, A. A. Tulapurkar and B. Muralidharan, IEEE Trans. Elec. Dev., (2016).

[3] A. Sharma, A. A. Tulapurkar and B. Muralidharan, Phys. Rev. Applied, 8, 064014, (2017).

[4] A. Agarwal and B. Muralidharan, Appl. Phys. Lett., 105,013104, (2014).

[5] A. Sharma, A. A. Tulapurkar and B. Muralidharan, Appl. Phys. Lett., 112, 192404, (2018).

[6] S. Mukherjee, P. Priyadarshi and B. Muralidharan, IEEE Trans. Elec. Dev., (2018).

August 21, 2019 at 2.30 pm in AG-69

Title :

Picturing the future of healthcare through molecular imaging 

Abstract :

In vivo molecular imaging has the unique advantage of noninvasively assessing cancer metabolism or providing functional real-time information relative to obtaining ex vivo pathological information from tissue biopsies. Two important molecular imaging modalities are Magnetic Resonance Imaging (MRI) and Positron Emission Tomography (PET). 

The first part of the presentation will focus on my research in the development of multiple diamagnetic MRI contrast agents and MRI methods that exploit Chemical Exchange Saturation Transfer (CEST) for the detection of enzyme activity (an important cancer biomarker) within in vivo tumor models of ovarian, colon and pancreatic cancers. This description will also demonstrate CEST MRI methods that have been used to correlate enzyme activity with tumor aggressiveness; to support planning for surgical resection of solid tumors; and to evaluate the early response to enzyme inhibitor treatments.  In conclusion, the first part of the talk represents a new paradigm for molecular imaging that can be translated to the radiology clinic to improve early diagnoses of cancer. 

The second part of the presentation will focus on my contribution to the field of molecular imaging of several infectious diseases such as HIV/SIV, cerebral malaria (CM), Ebola virus disease, and Marburg hemorrhagic fever, using both MRI and PET imaging modalities. The overarching goal of these studies was to develop neuroimaging biomarkers that are useful for detecting CNS involvement prior to display of clinical symptoms. These studies with a transgenic rat model and SIV rhesus macaque models have identified dopaminergic and serotonergic neurotransmitter biomarkers and have evaluated the role of neuroinflammation in an SIV-model of encephalitis. In a related study with a CM mouse model, we used MRI to evaluate the neuropathology of the disease.  We demonstrated, for the first-time, that reversal of clinical symptoms such as edema can occur with a glutamine antagonist, JHU-083, thus suggesting a possible drug candidate for CM therapy. These studies hope to convey to the audience the growing importance of molecular imaging in unraveling early details of the disease pathology, and to recognize potential opportunities for treatment for these diseases. 

 

The remaining talk will focus on harnessing molecular imaging techniques such as MRI for evaluating other biomarkers of the tumor microenvironment such as extracellular tumor pH, as well as new imaging modalities such as Photoacoustic tomography for improvement in cancer surgery. 

 

August 20, 2019 at 2.30 pm in AG-69

Title :

Picturing the future of healthcare through molecular imaging 

Abstract :

In vivo molecular imaging has the unique advantage of noninvasively assessing cancer metabolism or providing functional real-time information relative to obtaining ex vivo pathological information from tissue biopsies. Two important molecular imaging modalities are Magnetic Resonance Imaging (MRI) and Positron Emission Tomography (PET). 

The first part of the presentation will focus on my research in the development of multiple diamagnetic MRI contrast agents and MRI methods that exploit Chemical Exchange Saturation Transfer (CEST) for the detection of enzyme activity (an important cancer biomarker) within in vivo tumor models of ovarian, colon and pancreatic cancers. This description will also demonstrate CEST MRI methods that have been used to correlate enzyme activity with tumor aggressiveness; to support planning for surgical resection of solid tumors; and to evaluate the early response to enzyme inhibitor treatments.  In conclusion, the first part of the talk represents a new paradigm for molecular imaging that can be translated to the radiology clinic to improve early diagnoses of cancer. 

The second part of the presentation will focus on my contribution to the field of molecular imaging of several infectious diseases such as HIV/SIV, cerebral malaria (CM), Ebola virus disease, and Marburg hemorrhagic fever, using both MRI and PET imaging modalities. The overarching goal of these studies was to develop neuroimaging biomarkers that are useful for detecting CNS involvement prior to display of clinical symptoms. These studies with a transgenic rat model and SIV rhesus macaque models have identified dopaminergic and serotonergic neurotransmitter biomarkers and have evaluated the role of neuroinflammation in an SIV-model of encephalitis. In a related study with a CM mouse model, we used MRI to evaluate the neuropathology of the disease.  We demonstrated, for the first-time, that reversal of clinical symptoms such as edema can occur with a glutamine antagonist, JHU-083, thus suggesting a possible drug candidate for CM therapy. These studies hope to convey to the audience the growing importance of molecular imaging in unraveling early details of the disease pathology, and to recognize potential opportunities for treatment for these diseases. 

 

The remaining talk will focus on harnessing molecular imaging techniques such as MRI for evaluating other biomarkers of the tumor microenvironment such as extracellular tumor pH, as well as new imaging modalities such as Photoacoustic tomography for improvement in cancer surgery. 

 

August 19, 2019 at 4.00 pm in AG-69

Title :

Protein degradation by a double-ring AAA+ protease: in singulo mechanisms of unfolding and translocation

Abstract :

 

ATP powered molecular motors play a crucial role in maintaining protein quality control in a cell and AAA+ proteases maintain protein homeostasis by degrading damaged and unneeded proteins. Single-molecule manipulation tools complement the biochemical experiments and provide deeper insights into the mechanisms of these molecular motors and their interaction with protein substrates. In this talk, I will discuss my recent work on mechanistic investigations of a double-ring AAA+ protease, E.coli ClpAP using single-molecule optical tweezers and determine the role of individual ATPase rings in protein unfolding and translocation. Our single-molecule studies provide new insight into the functional importance of the D1 ring of ClpA and the role of coordination between the two AAA+ rings. Also, the differences in translocation from N- and -C termini indicate that the enzyme can recognize subtle differences in direction of the polypeptide track. In addition, I will elucidate the paramount role of local stability of a substrate in protein degradation and provide clues as to how the placement of degradation signals on a substrate may evolve to minimize the energetic cost of degradation.

References:

Hema Chandra Kotamarthi, Robert Sauer, Tania Baker. “The non-dominant AAA+ ring in the ClpAP protease functions as an anti-stalling motor to accelerate protein unfolding and translocation” (Pre-peer reviewed version at bioarXiv: https://doi.org/10.1101/585554)

Adrian Olivares*, Hema Chandra Kotamarthi*, Benjamin Stein, Robert Sauer, Tania Baker, “Effect of directional pulling on mechanical protein degradation by ATP-dependent proteolytic machines”, Proceedings of National Academy of Sciences, USA, 2017, Vol 114, E6306-E6313. * Equal Contribution.

August 13, 2019 at 2.30 pm in AG-80

Title :

Evaluation of Photocatalytic Activity Over g-C3N4 Coated DFNS and the Role of Interface

July 30, 2019 at 2.30 pm in AG-69

Title :

Small Molecule Activation at Transition Metal Centers: Structure-Function Correlations

Abstract :

Small molecule activation constitutes one of the main frontiers of inorganic and organometallic chemistry, with much effort directed towards the development of new processes for the selective and sustainable transformation of abundant small molecules such as dioxygen (O2), water (H2O), hydrogen peroxide (H2O2) or protons (H+) into high-value chemical feedstocks and energy resources. Because nature mostly uses metal ions to activate these relatively inert molecules and modulate their reactivity, much inspiration for the field has come from bioinorganic chemistry. This talk will focus on some of the recent highlights from our group on homogenously catalyzed bioinspired activation of small molecules, as well as stoichiometric reactions that further our understanding towards such ends. It will cover many aspects of small molecule activation including: organometallic chemistry, spectroscopy, synthesis, and detailed mechanistic studies involving trapping of reactive intermediates. The demonstrated examples will help to emphasize the continuous effort of our group in uncovering the structure-reactivity relationships of biomimetic model complexes, which may allow vital insights into the prerequisites necessary for the design of efficient catalysts for the selective functionalization of unactivated C–H bonds, O2/H2O/H2O2 activations, or H+ reductions by using cheap and readily available first-row transition metals under ambient conditions.

 

July 29, 2019 at 4.00 pm in AG-69

Title :

Computational investigation of the effect   of copper coordination and native disulfide bond   on the mechanical unfolding   pathways of Azurin

July 22, 2019 at 4.00 pm in AG-69

Title :

Can EPR be used to probe solid-liquid phase transitions in confined systems?

Abstract :

Study of systems such as water under confined conditions is actively pursued because of its relevance to real systems, such as cells, microorganisms, etc. In this regard, EPR spectroscopy offers a convenient route due to its excellent sensitivity to micro viscosity and penetrability power.  When used as a probe-based spectroscopy, however, the probe-system interactions need to be thoroughly examined beforehand. In this work, we consider a specific property: solid⇌liquid transition of water, and ask a fundamental question, “Can EPR detect the freezing of water at its conventional freezing point in bulk/confined conditions?”   Our work convincingly demonstrates that the spin probe can itself induce liquid domains in ice, which could be mistaken as a depression in the freezing point. We propose a theory to account for these solute induced perturbations. Finally, it will be discussed how the proposed theory can be applied to the extreme dilution case of a solution containing a single solute molecule.   

References

1.Thangswamy, M.; Maheshwari, P.; Dutta, D.; Rane, V.*; Pujari, P. K. J. Phys. Chem. A 2018, 122, 5177-5189.

2.Thangswamy, M.; Maheshwari, P.; Dutta, D.; Rane, V.*; Pujari, P. K. J. Phys. Chem. C 2019, 123, 11244-11256.

 

July 18, 2019 at 2.30 pm in AG-80

Title :

Biophysical characterization of DNA damage proteins from Rice Plant

Abstract :

DNA damage in living cells is repaired by two main pathways, homologous recombination (HR) and non-homologous end joining (NHEJ). The proteins involved in HR pathway have been widely studied in eukaryotes. The MRX/N complex which consists of Mre11, Rad50 and Xrs2 in case of yeast and Nbs1 for vertebrates, are the first responders to double strand breaks. This complex scans the DNA double strand for a break, and binds to the broken DNA ends as soon as a break occurs. The Mre11 protein of the MRN complex is highly conserved in eukaryotes. Rad52 (Radiation sensitive 52) belongs to a different group of important genes, and is found to be highly conserved across different species. Until lately, it was believed that RAD52 is absent in plant systems. However, recent genetic studies have pointed out the presence of RAD52 homologues in plants, though these have not yet been characterized biochemically. 

In the current study, the biochemical properties of rice OsMre11 and OsRad52 protein were analysed. These proteins were over-expressed in Escherichia coli over expression host cells and the proteins purified. The identity of purified OsMre11 and OsRad52 protein was confirmed via peptide mass fingerprinting. DNA binding assays showed that the purified proteins were able to bind to different forms of DNA. Purified OsMre11 protein exhibited nuclease properties, which was promoted by presence of manganese as a co- factor. Gel filtration and native PAGE analysis indicated that the OsRad52 protein in its native state probably formed an undecameric structure. Purified OsRad52 mediated the renaturation of complementary single strands into duplex DNA via both agarose gel and FRET based assays. Hence concluding that both OsMre11 and OsRad52 proteins, binds to ssDNA/dsDNA for mediating important functions like nucleolytic cleavage and renaturation during homologous recombination. This study represents the first report on biochemical properties of OsMre11 and OsRad52 protein from important crop like rice, which shall help in dissecting the recombination and repair machinery in plant systems.

 

July 15, 2019 at 4.00 pm in AG-69

Title :

The response of blue copper protein to changes in beta sheet connectivity