01512nas a2200157 4500008004100000022001400041245012700055210006900182260007100251300001400322490000600336520084200342100002401184700001801208856012801226 2014 eng d a1948-718500aExperimental determination of the electrostatic nature of carbonyl hydrogen-bonding interactions using IR-NMR correlations0 aExperimental determination of the electrostatic nature of carbon a1155 16TH ST, NW, WASHINGTON, DC 20036 USAbAMER CHEMICAL SOCcAUG a3211-32150 v53 a

Hydrogen-bonding plays a fundamental role in the structure, function, and dynamics of various chemical and biological systems. Understanding the physical nature of interactions and the role of electrostatics in hydrogen-bonding has been the focus of several theoretical and computational research. We present an experimental approach involving IR-C-13 NMR correlations to determine the electrostatic nature of carbonyl hydrogen-bonding interactions. This report provides a direct experimental evidence of the classical nature of hydrogen-bonding interaction in carbonyls, independent of any theoretical approximation. These results have important implications in chemistry and biology and can be applied to probe the reaction mechanisms involving carbonyl activation/stabilization by hydrogen bonds using spectroscopic techniques.

1 aKashid, Somnath, M.1 aBagchi, Sayan uhttps://library.ncl.res.in/content/experimental-determination-electrostatic-nature-carbonyl-hydrogen-bonding-interactions-002487nas a2200181 4500008004100000022001400041245009500055210006900150260007100219300001600290490000800306520178100314100002402095700002102119700001802140700001902158856012802177 2015 eng d a1520-610600aCosolvent effects on solute-solvent hydrogen-bond dynamics: ultrafast 2D IR investigations0 aCosolvent effects on solutesolvent hydrogenbond dynamics ultrafa a1155 16TH ST, NW, WASHINGTON, DC 20036 USAbAMER CHEMICAL SOCcDEC a15334-153430 v1193 a

Cosolvents strongly influence the solute-solvent interactions of biomolecules in aqueous environments and have profound effects on the stability and activity of several proteins and enzymes. Experimental studies have previously reported on the hydrogen-bond dynamics of water molecules in the presence of a cosolvent, but understanding the effects from a solute's perspective could provide greater insight into protein stability. Because carbonyl groups are abundant in biomolecules, the current study used 2D IR spectroscopy and molecular dynamics simulations to compare the hydrogen-bond dynamics of the solute's carbonyl group in aqueous solution, with and without the presence of DMSO as a cosolvent. 2D IR spectroscopy was used to quantitatively estimate the time scales of the hydrogen-bond dynamics of the carbonyl group in neat water and 1:1 DMSO/water solution. The 2D IR results show spectral signatures of a chemical exchange process: The presence of the cosolvent was found to lower the hydrogen-bond exchange rate by a factor of 5. The measured exchange rates were 7.50 X 10(11) and 1.48 X 10(11) s(-1) in neat water and 1:1 DMSO/water, respectively. Molecular dynamics simulations predict a significantly shorter carbonyl hydrogen-bond lifetime in neat water than in 1:1 DMSO/water and provide molecular insights into the exchange mechanism. The binding of the cosolvent to the solute was found to be accompanied by the release of hydrogen-bonded water molecules to the bulk. The widely different hydrogen-bond lifetimes and exchange rates with and without DMSO indicate a significant change in the ultrafast hydrogen-bond dynamics in the presence of a cosolvent, which, in turn, might play an important role in the stability and activity of biomolecules.

1 aKashid, Somnath, M.1 aJin, Geun, Young1 aBagchi, Sayan1 aKim, Yung, Sam uhttps://library.ncl.res.in/content/cosolvent-effects-solute-solvent-hydrogen-bond-dynamics-ultrafast-2d-ir-investigations-002608nas a2200205 4500008004100000022001400041245012400055210006900179260007100248300001400319490000800333520180600341100001602147700001802163700002402181700002502205700002302230700001802253856013102271 2016 eng d a1520-610600aCorrelating Nitrile IR frequencies to local electrostatics quantifies noncovalent interactions of peptides and proteins0 aCorrelating Nitrile IR frequencies to local electrostatics quant a1155 16TH ST, NW, WASHINGTON, DC 20036 USAbAMER CHEMICAL SOCcMAY a4034-40460 v1203 a

Noncovalent interactions, in particular the hydrogen bonds and nonspecific long-range electrostatic interactions are fundamental to biomolecular functions. A molecular understanding of the local electrostatic environment, consistently for both specific (hydrogen-bonding) and nonspecific electrostatic (local polarity) interactions, is essential for a detailed understanding of these processes. Vibrational Stark Effect (VSE) has proven to be an extremely useful method to measure the local electric field using infrared spectroscopy of carbonyl and nitrile based probes. The nitrile chemical group would be an ideal choice because of its absorption in an infrared spectral window transparent to biomolecules, ease of site-specific incorporation into proteins, and common occurrence as a substituent in various drug molecules. However, the inability of VSE to describe the dependence of IR frequency on electric field for hydrogen-bonded nitriles to date has severely limited nitrile's utility to probe the noncovalent interactions. In this work, using infrared spectroscopy and atomistic molecular dynamics simulations, we have reported for the first time a linear correlation between nitrile frequencies and electric fields in a wide range of hydrogen-bonding environments that may bridge the existing gap between VSE and H-bonding interactions. We have demonstrated the robustness of this field-frequency correlation for both aromatic nitriles and sulfur-based nitriles in a wide range of molecules of varying size and compactness, including small molecules in complex solvation environments, an amino acid, disordered peptides, and structured proteins. This correlation, when coupled to VSE, can be used to quantify noncovalent interactions, specific or nonspecific, in a consistent manner.

1 aDeb, Pranab1 aHaldar, Tapas1 aKashid, Somnath, M.1 aBanerjee, Subhrashis1 aChakrabarty, Suman1 aBagchi, Sayan uhttps://library.ncl.res.in/content/correlating-nitrile-ir-frequencies-local-electrostatics-quantifies-noncovalent-interactions01875nas a2200193 4500008004100000022001400041245009900055210006900154260007100223300001400294490000600308520115000314100001801464700002401482700001601506700001801522700001801540856012301558 2016 eng d a1948-718500aPick and choose the spectroscopic method to calibrate the local electric field inside proteins0 aPick and choose the spectroscopic method to calibrate the local  a1155 16TH ST, NW, WASHINGTON, DC 20036 USAbAMER CHEMICAL SOCcJUL a2456-24600 v73 a

Electrostatic interactions in proteins play a crucial role in determining the structure function relation in biomolecules. In recent years, fluorescent probes have been extensively employed to interrogate the polarity in biological cavities through dielectric constants or semiempirical polarity scales. A choice of multiple spectroscopic methods, not limited by fluorophores, along with a molecular level description of electrostatics involving solute-solvent interactions, would allow more flexibility to pick and choose the experimental technique to determine the local electrostatics within protein interiors. In this work we report that ultraviolet/visible-absorption, infrared-absorption, or C-13 NMR can be used to calibrate the local electric field in both hydrogen bonded and non-hydrogen bonded protein environments. The local electric field at the binding site of a serum protein has been determined using the absorption wavelength as well as the carbonyl stretching frequency of its natural steroid substrate, testosterone. Excellent agreement is observed in the results obtained from two independent spectroscopic techniques.

1 aHaldar, Tapas1 aKashid, Somnath, M.1 aDeb, Pranab1 aKesh, Sandeep1 aBagchi, Sayan uhttps://library.ncl.res.in/content/pick-and-choose-spectroscopic-method-calibrate-local-electric-field-inside-proteins01961nas a2200181 4500008004100000245013300041210006900174260000800243300001400251490000600265520127600271100002401547700002101571700002301592700001901615700001801634856012701652 2017 eng d00aTwo-dimensional infrared spectroscopy reveals cosolvent-composition-dependent crossover in intermolecular hydrogen bond dynamics0 aTwodimensional infrared spectroscopy reveals cosolventcompositio cAPR a1604-16090 v83 aCosolvents have versatile composition-dependent applications in chemistry and biology. The simultaneous presence of hydrophobic and hydrophilic groups in dimethyl sulfoxide (DMSO), an industrially important amphiphilic cosolvent, when combined with the unique properties of water, plays key roles in the diverse fields of pharmacology, cryoprotection, and cell biology. Moreover, molecules dissolved in aqueous DMSO exhibit an anomalous concentration-dependent nonmonotonic behavior in stability and activity near a critical DMSO mole fraction of 0.15. An experimental identification of the origin of this anomaly can lead to newer chemical and biological applications. We report a direct spectroscopic observation of the anomalous behavior using ultrafast twodimensional infrared spectroscopy experiments. Our results demonstrate the cosolventconcentration-dependent nonmonotonicity arises from nonidentical mechanisms in ultrafast hydrogen-bond-exchange dynamics of water above and below the critical cosolvent concentration. Comparison of experimental and theoretical results provides a molecular-level mechanistic understanding: a distinct difference in the stabilization of the solute through dynamic solute solvent interactions is the key to the anomalous behavior.1 aKashid, Somnath, M.1 aJin, Geun, Young1 aChakrabarty, Suman1 aKim, Yung, Sam1 aBagchi, Sayan uhttps://library.ncl.res.in/content/two-dimensional-infrared-spectroscopy-reveals-cosolvent-composition-dependent-crossover01365nas a2200205 4500008004100000022001400041245006300055210006300118260000800181300001400189490000800203520073300211100002400944700002100968700001700989700001901006700002101025700001801046856009501064 2019 eng d a1520-610600aArresting an unusual amide tautomer using divalent cations0 aArresting an unusual amide tautomer using divalent cations cOCT a8419-84240 v1233 a

Ion-specific effects on peptides and proteins are key to biomolecular structure and stability. The subtle roles of the cations are far less understood, compared to the pronounced effects of the anions on proteins. Most importantly, divalent cations such as Ca2+ and Mg2+ are crucial to several biological functions. Herein, we demonstrate that an amide-iminolate equilibrium is triggered by the binding of the divalent cations to the amide oxygen in aqueous solution. The excellent agreement between the experimental and theoretical results confirms the arrest of an unusual amide tautomer by the divalent cations, which is a rarely known phenomenon that might open up an array of applications in chemistry and biology.

1 aKashid, Somnath, M.1 aSingh, Reman, K.1 aKwon, Hyejin1 aKim, Yung, Sam1 aMukherjee, Arnab1 aBagchi, Sayan uhttps://library.ncl.res.in/content/arresting-unusual-amide-tautomer-using-divalent-cations02097nas a2200229 4500008004100000022001400041245015800055210006900213260000800282300001400290490000800304520125600312100002301568700001901591700001801610700001601628700002301644700002701667700002401694700001801718856013101736 2019 eng d a1520-610600aHydrocarbon chain-length dependence of solvation dynamics in alcohol-based deep eutectic solvents: a two-dimensional infrared spectroscopic investigation0 aHydrocarbon chainlength dependence of solvation dynamics in alco cNOV a9355-93630 v1233 a

Deep eutectic solvents (DESs) have gained popularity in recent years as an environmentally benign, inexpensive alternative to organic solvents for diverse applications in chemistry and biology. Among them, alcohol-based DESs serve as useful media in various applications due to their significantly low viscosity as compared to other DESs. Despite their importance as media, little is known how their solvation dynamics change as a function of the hydrocarbon chain length of the alcohol constituent. In order to obtain insights into the chain-length dependence of the solvation dynamics, we have performed two-dimensional infrared spectroscopy on three alcohol-based DESs by systematically varying the hydrocarbon chain length. The results reveal that the solvent dynamics slows down monotonically with an increase in the chain length. This increase in the dynamic timescales also shows a strong correlation with the concomitant increase in the viscosity of DESs. In addition, we have performed molecular dynamics simulations to compare with the experimental results, thereby testing the capacity of simulations to determine the amplitudes and timescales of the structural fluctuations on fast timescales under thermal equilibrium conditions.

1 aChatterjee, Srijan1 aGhosh, Deborin1 aHaldar, Tapas1 aDeb, Pranab1 aSakpal, Sushil, S.1 aDeshmukh, Samadhan, H.1 aKashid, Somnath, M.1 aBagchi, Sayan uhttps://library.ncl.res.in/content/hydrocarbon-chain-length-dependence-solvation-dynamics-alcohol-based-deep-eutectic-solvents06213nas a2200217 4500008004100000022001400041245009500055210006900150260000800219300001400227490000800241520546200249100002405711700002105735700001705756700001905773700001905792700002105811700001805832856014505850 2020 eng d a1520-610600aReply to “comment on ‘arresting an unusual amide tautomer using divalent cations’”0 aReply to comment on arresting an unusual amide tautomer using di cDEC a479–4830 v1253 a

In our publication, we assigned the blue-shifted shoulder of N-methylacetamide (NMA) in the infrared (IR) spectrum (∼1645 cm–1) to an iminolate tautomer stabilized in the presence of divalent metal cations (e.g., 5 M Ca2+).(1) Cremer and co-workers comment that this shoulder arises from the dehydration of the amide oxygen upon interaction with the metal cations.(2,3) Their assignment is based on three interesting experimental observations: (1) the IR spectrum of 15N-isotope-labeled NMA does not show any considerable red-shift compared to that of NMA; (2) a new peak appears for NMA at 1680 cm–1 in the presence of 1 M DCl, which shows a 17 cm–1 red-shift for 15N-labeled NMA; and (3) the IR spectrum of acetone C═O stretch also demonstrates a blue-shifted shoulder in the presence of a high concentration of CaCl2.

1 aKashid, Somnath, M.1 aSingh, Reman, K.1 aKwon, Hyejin1 aSeol, Jin, Gyu1 aKim, Yung, Sam1 aMukherjee, Arnab1 aBagchi, Sayan uhttps://library.ncl.res.in/content/reply-%E2%80%9Ccomment-%E2%80%98arresting-unusual-amide-tautomer-using-divalent-cations%E2%80%99%E2%80%9D