Molecular Structure and Weak Interactions Explored by Broadband Microwave Spectroscopy
Microwave spectroscopy allows details of structure to be measured for molecules and complexes which are isolated in the gas phase. One aim is to quantify weak interactions with high selectivity such that intrinsic character can be separated from effects of a solvent or matrix. This theme will be illustrated through recent studies of molecules containing imidazole. It will be shown that two isomers of a complex formed between this molecule and water can be isolated and spectroscopically-characterised in the gas phase. A second aim is to explore the gas phase chemistry prompted by laser vaporisation of solids in the presence of a mixture of chemical precursors, a process known to allow the generation of small molecules that can be found in interstellar and circumstellar environments. Laser vaporisation of platinum in the presence of gaseous hydrocarbons allows very efficient generation of PtC3, an atypical and exotic platinum carbene which has structural similarities with the oxycarbon species, OC3. Experiments are performed using a unique broadband rotational spectrometer that allows the simultaneous observation of many rotational transitions across a broad bandwidth.
Distribution of Isomerized and Racemized Amyloid b Isoforms in the Sporadic Alzheimer’s Disease using Ion-Mobility Mass Spectrometry
Extracellular amyloid plaques and intracellular neurofibrillary tangles are the pathological hallmarks of Alzheimer’s Disease (AD). It takes on average 19 years for amyloid b (Ab) peptides to deposit as insoluble plaques from onset to clinical dementia symptoms in AD. Such long-lived proteins and peptides without degradation and clearance can undergo further post-translational modifications (PTM). Several biochemical and analytical approaches have estimated very high degree of isomerization and racemization of Asp and Ser residues in Ab purified from the insoluble plaques, along with sequential loss of the N-terminal amino acids. In this study we have characterized the most common isomerization and racemization of the Asp-1 and Asp-7 residues of the Ab peptides present in AD brain based on both their chromatographic resolution as well as their collisional cross section (CCS) using high resolution ion mobility (IM) Q-TOF mass spectrometer (Agilent 6560). Using stable isotope labeled peptides we have also quantified the amount of these isomers/racemers in the different fractionated biochemical pools of the temporal cortex grey matter of human AD and control brains. Distribution of these isomerized and racemized peptides change from lower levels in the soluble/peripheral memebraneous to higher levels in the insoluble/aggregated debris in AD brain, also indicating loss in the biochemical exchange of the pool of Ab with the progression of the disease. These findings have implications in Ab neurotoxicity, oligomerization, structures of amyloid fibrils present in the AD brain as well establishing CSF/blood-based biomarkers.
Vibrational spectroscopy of biological systems at the micro and nano level - RERS, SERS, TERS & AFM-IR
Raman spectroscopy is an excellent tool for interrogating biomolecules or biological systems in natural environments because water is such a weak Raman scatterer. This is particularly the case when there are chromophoric materials such as hemes, chlorophyll, carotenes that are strong scatterers or give rise to resonance Raman. Over a number of years we have applied Raman, Resonance Raman, Surface Enhanced Raman and Tip enhanced Raman spectroscopies to live cells such as erythrocytes in order to understand and develop probes for disease states. A number of these studies will be used to highlight instrumental and sampling techniques and data analysis in Raman spectroscopy of biosystems. Infrared spectroscopy also has a role, especially nano-IR and a study of DNA methylation will be used to show the power of nano-IR
Role of Acetylation at Active Site Lysine in Maintaining the Functional State of CDK1-Cyclin B Complex
Planarization of Anthracene fused Cyclooctatetraene
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.
1. S. K. Ghosh, R. Singh and S. M. Date, Chem. Commun., 2003, 636.
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.
4. R. Singh and S. K. Ghosh, Chem. Commun., 2011, 47, 10809.
5. G. S. Naidu, R. Singh and S. K. Ghosh, RSC Adv., 2016, 6, 37136.
6. R. Singh, G. S. Naidu and S. K. Ghosh, Proc. Natl. Acad. Sci., India, Sect. A Phys. Sci., 2016, 86, 619.
7. G. S. Naidu, R. Singh, M. Kumar and S. K. Ghosh, J. Org. Chem., 2017, 82, 3648.
8. G. S. Naidu, R. Singh and S. K. Ghosh, Synlett, 2018, 29, 282.
Multiphoton femtosecond laser spectroscopy of anisotropic molecular probes
The talk presents a review of theoretical and experimental investigations of polarized fluorescence in anisotropic molecular probes excited via two-color two-photon transitions by femtosecond laser pulses.
The molecular probes under study were small biomolecules which are of importance for bio-medical applications: indole, tryptophan, and NADH (nicotinamide adenine dinucleotide). The polarized fluorescence was excited in molecular solutions by simultaneous absorption of two laser photons with different and variable wavelengths thus allowing for tuning of the total excitation energy in the range 4,04-7,09 eV. By alternating the polarization of each of the three photons involved in the photoprocess a set of molecular parameters describing the photoprocess dynamics were determined. Analysis of the results obtained was performed on the basis of ab initio computations of excited state molecular structure and transition dipole moments.
As pointed out in the talk, the molecular parameter values are very sensitive to the molecular microenvironment thus allowing for investigation of thin details of enegry transfer processes in excited molecules characterized by: anisotropic distribution of molecular axes, lifetimes, rotation correlation times, and the dynamics of nonadiabatic transitions between different potential energy surfaces. As shown, investigation of polarized fluorescence from molecular probes imbedded into biological structures opens a new information channel on protein structure, folding, hydration, and on the mechanizms of redox reactions in living organisms.
1. P. S. Shternin, K.-H. Gericke, O. S. Vasyutinskii, Molecular Physics, 2010, 108(7), 813.
2. S. Denicke, K.-H. Gericke, A. G. Smolin, P. S. Shternin, O. S. Vasyutinskii, J. Phys. Chem. A 2010, 114, 9681.
3. S. Herbrich, K.-H. Gericke, A. G. Smolin, O. S. Vasyutinskii, J. Phys. Chem. A. 2014, 118, 5248.
4. S. Herbrich, T. Al-Hadhuri, K.-H. Gericke, P. S. Shternin, A. G. Smolin, O. S. Vasyutinskii, J. Chem. Phys. 2015, 142, 024310.
5. M. E. Sasin, A. G. Smolin, K.-H. Gericke, E. Tokunaga, O. S. Vasyutinskii, PCCP, 2018, V.20, pp. 19922.
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
L-Amino acid Based Polyester Nanocarriers for Drug Delivery and Bio-imaging
The past generation therapeutic agents are increasingly failing in combating new-age threats. Therapeutics based on polymers are advantageous as they possess advanced targeting, can target hard to reach agents, and carry multiple cargos of conflicting nature. These can be extremely selective, owing to several phenomena such as Enhanced Permeation (EPR) effect and carrying multiple cargoes in a single particle, which can have synergistic effects, leaving them more potent than any of the medicine alone.
L-Amino acid-based synthetic polypeptides non-peptides are extensively explored for biomedical applications owing to their structural diversity and biocompatibility. My talk is aimed to explore new classes of amphiphilic and biodegradable polyester and their fluorescent nano-assemblies based on natural L-aspartic acid resources for accomplishing anticancer drug delivery and intracellular bioimaging in cancer cells. These polymers were designed with the dual response to acidic conditions and enzyme-rich environment stimuli. Different therapeutically active drugs were loaded into the polymer scaffolds, and their cytotoxicity was studied in the cancer cell lines.
The uptakes of these drugs were monitored using confocal microscopy. L-amino acid-based amphiphilic luminescent polyester was developed using π- conjugated oligo-phenylenevinylene (OPV) custom made diols, while Aggregation induced emission (AIE) capable hydroxyl functionalized tetraphenylethyelene (TPE) diol was tailor-made through multi-step reaction and was subjected to melt transesterification with L-aspartic acid monomer to yield new blue-luminescent amphiphilic polyesters.
Hydroxyl and carboxylic functionalized polyesters were also synthesized. The hydrophilic hydroxyl and carboxylic groups along with the hydrophobic aliphatic backbone made these polymer amphiphilic in nature and enabled these to self-assemble into spherical nanoparticles in water, which exhibited superior encapsulation capabilities to load wide ranges of both water-soluble and water-insoluble anticancer drugs and fluorophores. The amphiphilic polyesters designed and developed based on L-aspartic acid residues presented in the talk are new entries as enzymatic-biodegradable polymers in the literature, and the custom-designed OPV-tagged and TPE-tagged fluorescent polymers are excellent nano-scaffolds for constructing a wide range of FRET probes with drugs and fluorophores which could be employed for early diagnostics of cancer and other bio-imaging applications. Thus, the work opens up a new platform of opportunities in the biomaterials arena based on L-Amino acid polymers.
Design and Development of Optical Probes for Tracking Essential and Toxic Metal Ions
Carbenes in a Supersonic Jet Expansion
Hydrogen Bond (HB) is one of the important intermolecular forces and is ubiquitous in Chemistry and Biology. Since it has strong directional nature it plays an important role in supramolecular chemistry as well as molecular recognition. These H-bonds play a vital role in determining the structure of proteins and supramolecules and there is evidence of these interactions in literature.
Among different reactive intermediates, Carbene being neutral and highly electron-deficient species play a significant role in various organic transformations. Hydrogen bonding that involves carbene as a hydrogen acceptor is very poorly documented in the literature.1
For instance, N-heterocyclic carbene carbon (singlet ground state) is highly nucleophilic due to adjacent nitrogen centres. Such electron-rich nucleophilic species can act as powerful Lewis bases. Water, being proton donor, can interact with Lewis bases like nucleophilic carbenes to form the strong hydrogen-bonded complex.
1.P. Costa, W. Sander, Angew. Chem. Int. Ed. 53 (2014), 5122-5125.
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)