Maneuvering the stability and reactivity of ‘Dendralenes”, an exciting class of oligo-enes for diversity oriented organic synthesis
Organic synthesis is mainly concerned with C-C and C-X (X = heteroatom) bond forming reactions. The biggest challenge is to perform them under strict control of regio-, stereo- and enantio-selectivity, and also to achieve diverse structural complexity in fewer steps. Carbon-carbon double bond (olefin) is an important synthon in organic chemistry for further C–C bond formation, diverse functional group generation and for construction of complex organic structures. Olefins also exhibit great structural diversity when several such bonds are put together in a molecule. Depending upon the type of connectivity of the ethylene units, conjugated polyenes can be classified into various classes. A geminal linkage results in a class of cross conjugated polyenes called as "Dendralenes". Despite being in existence in Nature and having been synthesized as early as in 1955, they remained "unmanageable" until the turn of this century mainly owing to their unpredictable stability and reactivity.
Due to the abundance of fused hetero- and carbocyclic ring systems in numerous bio-active compounds, such motifs have intrigued synthetic organic chemists. Besides, an efficient synthesis of such architecturally complex scaffolds is an uphill task and hence poses a formidable challenge. In this regard, dendralenes are fascinating molecules because they possess huge potential for the quick generation of diverse and complex multicyclic scaffolds when subjected to tandem Diels–Alder (DA) reactions, also known as diene transmissive Diels–Alder (DTDA) sequences. But their synthesis is a tall order.
The chronicles of our roller-coaster journey and systematic approach beginning from the development of new olefination protocols, synthesis of extremely unstable, non-isolable dendralenes through moderately stable examples and finally, highly functionalized stable dendralenes will be presented. The attributes affecting their stability and reactivity have been recognized. Also, how these dendralenes, upon judicious maneuvering, can be engaged in a DTDA sequence, thus harnessing their full potential by construction of a small but diverse library of complex frameworks in a quick and efficient manner, with step and atom economy will be discussed.
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2. S. M. Date and S. K. Ghosh, Angew. Chem. Int. Ed., 2007, 46, 386.
3. R. Singh and S. K. Ghosh, Org. Lett., 2007, 9, 5071.
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Medium Matters: Dynamics of Molecules in a Confined Space
From time immemorial it is well known that curtailment of freedom often leads to changes in the behaviour of living beings. Similar restriction of freedom leads to selectivity in the chemical behaviour of molecules embedded in biological systems. Extending these well-known behaviours, supramolecular chemists have established that even small molecules upon confinement in synthetic hosts exhibit behaviour distinctly different from the ones in a bulk isotropic solution.
In this lecture the role a “Medium” in bringing about changes in the well-established behaviour of excited molecules would be illustrated with select examples. Results of steady state and ultrafast experiments will be presented that highlight how the confinement alters the excited state dynamics of molecules such as stilbenes, azobenzenes, anthracene, dibenzyl ketones etc. Another reaction to be discussed concerns with electron transfer and spin transfer that play a fundamental role in a number of biological events including photosynthesis. Examples and ultrafast dynamics of electron and spin transfer between a confined and a free molecule would be presented.
The main message of the talk is that molecules like humans behave differently when confined within synthetic cages.
 V. Ramamurthy, S. Jockusch and M. Porel, Langmuir, 2015, 31, 5554-5570
 V. Ramamurthy, Acc. Chem. Res. 2015, 48, 2904-2917.
 A. Mohan Raj, M. Porel, P. Mukherjee, X. Ma, R. Choudhury, E. Galoppini, P. Sen and V. Ramamurthy, J. Phys. Chem. C, 2017, 121, 20205−20216.
 C-H. Chuang, M. Porel, R. Choudhury, C. Burda and V. Ramamurthy, J. Phys. Chem. B, 2018, 122, 328−337.
 C. J. Otolski, A. Mohan Raj, V. Ramamurthy and C.G. Elles, J. Phys. Chem. Lett. 2019, 10, 121−127
Utility of Natural Product Biosynthetic Enzymes for Drug Discovery
Dr. Singh is interested in the structural diversification of natural products to develop drug candidates with biological activity against cancer and infectious diseases. Her research focuses on utility and rationally engineering enzymes to modify substrate acceptability profiles and develop novel drugs with improved activity. Natural products and their derivatives account for about three-quarters of the approved drugs on the market. Using conventional chemical synthesis to structurally diversify complex natural products can be challenging. To overcome this challenge, the Singh Laboratory engineers enzymes for proficiency, promiscuity, or altered substrate specificity, capable of performing regio- and stereo-specific transformations in order to generate a library of new drug-like molecules for screening. Recently, she has developed a platform for drug discovery through engineering the substrate specificity of prenyltransferases, a class of natural product late-stage modification enzymes. In this seminar, she will discuss the development of this prenyltransferase-based chemoenzymatic platform to diversify natural products with a library of novel substrates in order to generate therapeutically relevant molecules with enhanced activity against antimicrobial-resistant bacterial strains. Dr. Singh obtained her PhD from the Tata Institute of Fundamental Research, and subsequently pursued post-doctoral research at the Memorial Sloan Kettering Cancer Center in the United States, and Utrecht University in the Netherlands.
Cell Permeable Ratiometric Fluorescent Sensor for Detecting Signal Mediating Phospholipids
Publishing from an Editor's Viewpoint - Insider Tips for Successful Submissions
Significance of defect engineering and hetero-junction engineering to improve the photoelectrochemical properties of ZnO nanorods photoanode
The significance of defect engineering in tuning the visible light driven photoelectrochemical properties due to alkali metal (Li, Na, K) doping into ZnO nanorods (NRs) photoanode is investigated. Large concentration of oxygen-vacancies introduced because of alkali doping serve as the light absorbing donor sites and also photoelectron recombination centres resulting enhanced photocurrent and hole separation in the valance band, respectively. The lattice strain developed in the nanorods due to doping contributes in easy electron transportation and mobility. Defect engineering also tunes the electronic structure of the photoanodes boosting charge carrier migration and reduced electron-hole pair recombination resulting enhanced oxygen evolution reaction. On the other hand, the design of multidimensional nano-heterostructures based photoelectrode is demonstrated by coupling the multilayered two-dimensional (2D) structure of MoS2 and MoO3 on the well aligned arrays of one-dimensional (1D) ZnO nanorods template expecting the effective synergic effects. The advantages of catalytically active sites of 2D layered structure of transition metal dichalcogenides/oxides is integrated with the distinctive dimensionality dependent phenomena of 1D structure to achieve enormous surface area for light harvesting and photoelectrochemical reaction along with favorable photocarrier dynamics required for water splitting.
K. Karmakar, A. Sarkar, K. Mandal and G. G.Khan. Investigating the role of oxygen vacancies and lattice strain defects on enhanced photoelectrochemical property of alkali metal (Li, Na and K) doped ZnO nanorods photoanodes. ChemElectroChem 2018, 5, 1147 –1152.
K. Karmakar, D. Maity, D. Pal, G. G. Khan and K. Mandal. Photo-induced Exciton Dynamics and Broadband Light Harvesting in ZnO Nanorod Templated Multilayered 2D MoS2/MoO3 Photoanodes for Solar Fuel Generation. (Under Review)
Electrocatalysis and gas solid catalysis by Pt ions in perovskites: A comparison between supported and the doped catalysts
In this work, La1-xSrxCoO3 perovskite have been used as a host oxide for Pt doping and Pt supported system. The solution combustion and chemical reduction method have been adopted for the catalyst synthesis. Three selected reactions have been investigated in detail during the studies, namely the oxygen evolution reaction (OER), formic acid electro-oxidation and CO oxidation. The catalytic and electro-catalytic differences between the Pt doped and Pt-supported system has been studied. It was found that there are significant differences between the Pt-doped and Pt-supported systems for electro-catalytic and catalytic reactions. Activity of the catalyst depends on the particular reaction selected for comparison. We hope that the results presented in this work are a worthwhile contribution to catalysis.
Donor-Acceptor materials and their applications in OLEDs and solar cells
Donor-acceptor-donor (D-A-D) materials having acridone as acceptor and carbazole as donor were synthesized for opto-electronic applications. Steady state and time dependent emission studied provided insight on their possible thermally activated delayed fluorescence (TADF) behaviour. The singlet-triplet energy gap (∆EST) was found to be as low 0.2eV. These materials were used green TADF emitters in organic light emitting diode (OLED) devices. Furthermore, an exciplex emission at 465 nm was observed in the blends of these D-A-D with polyvinylcarbazole (PVK). OLEDs fabricated with blend showed blue electroluminescence which is matching well with the exciplex photoluminescence. Apart from D-A-D in OLEDs, application of new class of high dipole moment materials in solar cell will also be discussed.
Leadership and Organization Development
The training on "Leadership and Organization Development" was about the development of the mindset for women Scientists/Technologists. It is necessary to learn various leadership skills for enhancement of organization development. The perspective was to nurture and grow Scientists/Technologists' skills to further increase the growth of their organizations. Working well with others would enhance the team productivity and create a positive environment in organizations. Scientists as Leaders in any organization are required to build teams, envisage change and create vision, mentor followers, and nurture a culture of excellence. Hence, this programme on "Leadership and Organization Development" (under the "DISHA Programme for women in Science") is designed to impart necessary skills for Scientists/Technologists to assume leadership role in efficient way.
The Electron Attachment Induced Radiation Damage to Genetic Materials : The Role of Water
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. Water has been shown to accelerate the process of radiation damage. 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.
B. Boudaïffa, P. Cloutier, D. Hunting, M. A. Huels, L. Sanche, Science (80. )., 2000, DOI:10.1126/science.287.5458.1658.
J. Ma, F. Wang, S. A. Denisov, A. Adhikary, M. Mostafavi, Sci. Adv., 2017, DOI:10.1126/sciadv.1701669.
 M. Mukherjee, D. Tripathi, A.K. Dutta, 2019 (to be communicated )
Cu2ZnSnS4: A potential photovoltaic material for low-cost thin film solar cell
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 %.
Targeted Prodrugs to Manipulate Copper Biology of Prostate Cancer
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.
(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.
Bispidine coordination chemistry – ligands for medicinal chemistry, bioinorganic modeling and oxidation catalysis
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).
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
Engineering Artificial Metalloenzyme for Enantioselective Catalysis
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.
Series “Quantum” Resistors: Design of “molecule like” spin-filtering using superlattices
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.
 N. Chatterji, A. A. Tulapurkar and B. Muralidharan, Appl. Phys. Lett., 105, 232410,(2014).
 A. Sharma, A. A. Tulapurkar and B. Muralidharan, IEEE Trans. Elec. Dev., (2016).
 A. Sharma, A. A. Tulapurkar and B. Muralidharan, Phys. Rev. Applied, 8, 064014, (2017).
 A. Agarwal and B. Muralidharan, Appl. Phys. Lett., 105,013104, (2014).
 A. Sharma, A. A. Tulapurkar and B. Muralidharan, Appl. Phys. Lett., 112, 192404, (2018).
 S. Mukherjee, P. Priyadarshi and B. Muralidharan, IEEE Trans. Elec. Dev., (2018).