TIFR
Department of Chemical Sciences
School of Natural Sciences

Calender

May 8, 2019 at 2.30 pm in AG-80

Title :

Using Microwave Pulses to Expand the Scope of DNP Enhanced Solid-State NMR Spectroscopy

Abstract :

 

Dynamic nuclear polarization has revolutionized the field of solid-state NMR by providing the sensitivity enhancement of orders of magnitude. Currently, most DNP experiments are performed using continuous-wave (CW) microwave irradiation near EPR frequency of the polarizing agents using dedicated gyrotrons. The CW-DNP mechanisms, i.e. solid-effect (SE), cross-effect (CE) and thermal mixing (TM) become less efficient at higher magnetic fields due to inefficient state mixing caused by large Zeeman splitting. Therefore, the signal enhancements achieved at high magnetic fields are well below the theoretical maximum of 658.
 
An alternative approach, which is recently gaining foothold, will be discussed. In this approach, microwave pulses with varying phase, length, amplitude and frequency are employed to obtain field independent electron-nuclear polarization transfer by fulfilling the required matching condition. Such methods require microwave irradiation with low duty cycle, which minimized the problem of sample heating that is prominent is CW-DNP experiments. Moreover, the paramagnetic effects, i.e. NMR line-broadening, signal quenching and relaxation enhancement, caused by the presence of a paramagnetic center can also be reversed using microwave pulses with frequency switching capabilities. I will show experimental evidences of reversal of paramagnetic effects at a magnetic field of 6.9 T and 4K temperature. 
 
At the end, I will talk about my future research plans focusing at developments and applications of the magnetic resonance techniques (NMR and DNP) to study materials and biological samples.  

May 7, 2019 at 2.30 pm in AG-80

Title :

Advancing the Magnetic Resonance Frontiers for the Study of Complex Molecules and Active Materials

Abstract :

Nuclear Magnetic Resonance (NMR) is a spectroscopic method that provides atomically resolved structural and dynamical information of systems from a vast category including organic and inorganic chemistry, materials and biology. The technique offers unique capabilities to study complex molecules that are insoluble and non-crystalline such as amyloid fibrils, membrane proteins, amorphous polymers, catalytic compounds, and battery materials etc. A major challenge in the applications of solid-state NMR spectroscopy is the intrinsically low sensitivity of the technique that practically restricts its use to a limited number of NMR active isotopes such as 1H, 19F, 31P, 13C, and 15N. Therefore, a number of practically relevant systems that in principle can be studied using solid-state NMR, remain out of its reach. 
 
I will present two approaches to address the problem of sensitivity in solid-state NMR. The first approach is development of new methods, i.e., radio frequency (RF) pulse sequences to probe NMR isotopes like 2H, 14N, 7Li etc.  that are difficult due to their less sensitivity (low gyromagnetic ration and/or less natural abundance) and large anisotropic interaction like quadrupolar coupling and chemical shift anisotropy. A new RF pulse sequence and its applications to biological and material samples with various challenging NMR isotopes will be discussed, demonstrating the versatility of the new method and its impact.  
 
In the second approach, I will discuss a rapidly emerging hyperpolarization technique known as dynamics nuclear polarization (DNP), which can enhance the sensitivity of NMR by orders of magnitude. DNP has already made a paradigm shift in solid-state NMR spectroscopy by enabling studies of systems like proteins in physiological conditions and materials with extremely insensitive NMR isotopes like 17O. However, the state-of-the-art DNP methods rely on exogenously added source of paramagnetic centers (typically stable nitroxide or carbon-based radicals) for the polarization. The scope of DNP can be further expanded by performing endogenous DNP using paramagnetic metal centers as the source of polarization to enhance sensitivity of the surrounding nuclear spins. Such metal centers are intrinsically present in systems like metalloproteins, metalloenzymes, energy harvesting materials and battery compounds. More importantly, endogenous DNP is a critical step towards performing “hyperfine DNP spectroscopy” to extract the local structural information directly from the electron-nuclear hyperfine interaction while detecting sensitivity enhanced NMR signal. Recent results using V4+ centers for the first time to enhance polarization of protons in the sample will be shown to illustrate the concept of hyperfine DNP spectroscopy.

May 3, 2019 at 2.30 pm in AG-69

Title :

Sensors and Chelators for Essential Transition Metal Ions

May 2, 2019 at 4.00 pm in AG-80

Title :

How membrane characteristics influence membrane protein conformation

Abstract :

Cell membranes not only maintain cell integrity, but possibly also influence the functioning of membrane proteins. Local membrane order and cholesterol content are two important factors, but they remain poorly understood.  Here, I have probed how the mode of interaction of Amylin (a disease causing peptide oligomer with high membrane affinity) is controlled by the nature of membrane. For this purpose, we have built a combined AFM-Confocal-FLIM-FCS set up and probed the accessibility of the terminals (N and C) and the extent of insertion in different membrane environments. We find that these parameters are highly dependent on the local lipid order. We also monitored the extent of depletion of cholesterol in presence and absence of amylin, and found that amylin resists the changes caused by cholesterol depletion and helps the membrane to retain its integrity. Thus, our study quantifies the strong reciprocal influence between membrane proteins and membranes, which has possible biological consequences.

May 1, 2019 at 2.30 pm in AG-69

Title :

Buoyant Microcapsules: Simple motility to Complex Autonomous Behavior

Abstract :

Nature has always been a great source of inspiration for the design of artificial materials with improved hierarchical organization, superior properties and smart functions. In this age of artificial intelligence and smart systems, chemists are increasingly looking to design active and adaptive materials taking inspiration from the various biological processes and their self-regulatory mechanisms which make ‘life’ possible. In this talk, I will illustrate with an example of a microcapsule with an entrapped gas bubble whose motility is governed by buoyancy forces, how we can design complex autonomous behavior into relatively simple systems. Our results show that microcapsules can be propelled by an active control of buoyancy forces and this buoyant motility can be used to trigger chemical reactions, simulate self-sorting behavior in microcapsule communities and achieve complex oscillatory motility.

References:

  1. B. A. Grzybowski & W. T. S. Huck, The Nanotechnology of Life-inspired Systems, Nat. Nanotechnol. 2016, 11, 585.
  2. B. V. V. S. P. Kumar, A. J. Patil & S. Mann, Enzyme-powered motility in buoyant organoclay/DNA protocells, Nat. Chem. 2018, 10, 1154.
  3. L. Rodriguez-Arco, B. V. V. S. P. Kumar, M. Li, A. J. Patil & S. Mann, Modulation of Higher-order Behaviour in Model Protocell Communities by Artificial Phagocytosis, Angew. Chem. Int. Ed. 2019, DOI: 10.1002/ange.201901469.

 

 

April 30, 2019 at 2.30 pm in AG-69

Title :

Advancement of Nanomaterials: Nanotherapeutics and Antibacterial Performance

Abstract :

       Carbon nanomaterials are promising in nature due to their higher surface area, known chemistry and ease of structural functionalization. A higher surface area and modulation of functionalities is the key to success to extend their potential in various domains. Present chemistry of graphene oxide (GO) synthesis is dominated by Hummer’s method and its modified versions. The non-reproducibility, variation in sources and physical reaction parameters affect size, degree of oxidation, nature, and type of oxo-functionalities. Furthermore, problems associated with its mass production demands development of better and easier synthetic protocols. In our lab, we are exploring safer, easier, less-energy intensive protocols for synthesis of GO and their advancement in biomedical applications.

       Nanotherapeutics is most appealing and viable approach to enhance the potential of existing drugs rather than designing and synthesizing new drug molecules to counter diseases. More recently, gene-based antitumor therapy demands smart engineering of effective vectors.

In this respect, we have explored biocompatible polymers tethered GO nanoconjugates as efficient nonviral vectors for gene-based cancer therapeutics. A promisable transfection and gene-knock down efficiency is revealed and results were compared with commercial vector. A pH-triggered release of siRNA from the vector-siRNA complex was studied to provide a mechanistic insight toward unloading of siRNA from the vector.

       In another work, enhancement in efficacy of traditional medicine with non-toxic surface modified metal oxide nanoparticles is explored. The nanoparticles are specially designed to allow sustained release of bound species to facilitate prolonged activity of drug.

 

       Additionally, pristine GO coatings synthesized from different routes revealed remarkable antimicrobial activity due to its specific surface-interface interactions with the bacteria, which is again a valuable addition at biomedical frontiers.

 

April 29, 2019 at 4.00 pm in AG-69

Title :

The interaction of neurotransmitters with lipid bilayer membranes

Abstract :

Recent studies have shown that serotonin, a major neurotransmitter in the mammalian brain, can bind directly to lipid membranes with high affinity. It has been suggested that this can contribute to signal transduction in a receptor independent fashion. We also hypothesize that this may have a role in membrane-amyloid interactions. Here we probe these possibilities by studying the effect of serotonin on an artificial ternary lipid bilayer and also on the membranes of living cells, using AFM and confocal imaging, and force spectroscopy. Our results show that direct interaction of serotonin with lipid bilayer membranes can alter their properties, which can have a significant effect on the ability of a cell to bind disease-associated proteins, and on the activity of generic membrane proteins. We infer that serotonin can effect cellular properties through a receptor-independent membrane mediated pathway.

April 25, 2019 at 4.00 pm in AG-80

Title :

Fluorescent Red Emitting Sensors for Imaging Signal Mediating Phospholipids

April 22, 2019 at 4.00 pm in AG-69

Title :

Predicting directional flexibility of protein from its crystal structure

Abstract :

Mechanical flexibility is found to be anisotropic in protein molecules. In order to understand complex role of protein in mechano-biology or develop new allosteric protein based nano-materials, anisotropic response of protein to uniaxial mechanical stress is needed to be understood in detail. In this talk I will propose an analytical framework to compute directional flexibility in terms of directional spring constant of proteins from its native state crystal structure. Our formalism includes Cα atom based coarse-grained Elastic Network Model (ENM) where we employed statistical propagation of error to obtain variance of a distance between two atoms from standard deviation of coordinates of the constituent atoms using ENM normal modes. Directional flexibility of Ubiquitin predicted in this way is almost ~ 70% accurate in comparison to that obtained from all atom explicit solvent Molecular Dynamics simulation. I will also discuss about tuning ENM potential to get better agreement on directional flexibility prediction. 

April 18, 2019 at 4.00 pm in AG-80

Title :

Amorphous Zeolitic Nanosponges as Heterogeneous Solid Catalysts

April 15, 2019 at 4.00 pm in AG-69

Title :

Towards understanding the structure of amyloids in the lipid membrane

April 12, 2019 at 2.30 pm in AG-69

Title :

A new GC Binder for Sequence-selective DNA Recognition

Abstract :

Click here

 

April 11, 2019 at 4.00 pm in AG-80

Title :

Elucidating Folding-Unfolding Pathways of Ubiquitin Family Proteins

April 9, 2019 at 2.30 pm in AG-69

Title :

Online Electrochemical Mass Spectrometry as A Tool to De-Convolute Catalysis, Instability and Efficacy of Protection Strategies

Abstract :

Limited stability of most electrode materials (EM) and electrolytes under stringent operating conditions is a matter of concern for the battery research community and industry. In past few years, it has been demonstrated that EMs degrade through their reactive interface with the electrolyte. Undesirable interfacial reactions result in formation of solid precipitates that impede the charge transfer and can serve as an active site for electrolyte consumption, anode corrosion and passivation, thereby, leading to inefficient lithium/sodium ion and metal-O2 batteries (LIB/SIB/LOB). Especially, the progress of high energy and high voltage batteries is mostly restricted by issues associated with the electrode/electrolyte interfacial instability and electro-chemomechanical degradation under the operation conditions. As a result, strategies that (1) stabilize the interface by designing a protection layer commonly known as “artificial solid electrolyte interface (ASEI)” and (2) that can electro/chemically catalyse the reactions and bring the potentials to lower values can significantly enhance battery performance by stabilizing the functional interface and addressing the deleterious reactions between electrode and electrolyte. Nevertheless, there is a dire need of in-operando and in-situ analytical tools to deconvolute the degradation paths to have targeted solutions based on the instability of the components. Online electrochemical mass spectrometry in synergy with solid state NMR can prove to be on such tool. 

April 8, 2019 at 4.00 pm in AG-69

Title :

Understanding the mechanism of binding between proteins in CDK1/cyclin-B/CKS-2 complex