02608nas 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-interactions01854nas a2200157 4500008004100000022001400041245008200055210006900137260007100206300001400277490000600291520125500297100001801552700001801570856010801588 2016 eng d a1948-718500aElectrostatic interactions are key to C=O n-pi* shifts: an experimental proof0 aElectrostatic interactions are key to CO npi shifts an experimen a1155 16TH ST, NW, WASHINGTON, DC 20036 USAbAMER CHEMICAL SOCcJUN a2270-22750 v73 a

Carbonyl n-pi* transitions are known to undergo blue shift in polar and hydrogen-bonding solvents. Using semiempirical expressions, previous studies hypothesized several factors like change in dipole moment and hydrogen-bond strength upon excitation to cause the blue shift. Theoretically, ground-state electrostatics has been predicted to be the key to the observed shifts, however, an experimental proof has been lacking. Our experimental results demonstrate a consistent linear correlation between IR (ground-state phenomenon) and n-pi* frequency shifts (involves both ground and excited electronic-states) of carbonyls in hydrogen-bonded and non-hydrogen-bonded environments. The carbonyl hydrogen-bonding status is experimentally verified from deviation in n-pi*/fluorescence correlation. The IR/n-pi* correlation validates the key role of electrostatic stabilization of the ground state toward n-pi* shifts and demonstrates the electrostatic nature of carbonyl hydrogen bonds. n-pi* shifts show linear sensitivity to calculated electrostatic fields on carbonyls. Our results portray the potential for n-pi* absorption to estimate local polarity in biomolecules and to probe chemical reactions involving carbonyl activation/stabilization.

1 aHaldar, Tapas1 aBagchi, Sayan uhttps://library.ncl.res.in/content/electrostatic-interactions-are-key-co-n-pi-shifts-experimental-proof01875nas 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-proteins02097nas 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-solvents02238nas a2200181 4500008004100000022001400041245012800055210006900183260000900252300001400261490000800275520156400283100002301847700001801870700001901888700001801907856013101925 2020 eng d a1520-610600aElectrostatic manifestation of micro-heterogeneous solvation structures in deep-eutectic solvents: a spectroscopic approach0 aElectrostatic manifestation of microheterogeneous solvation stru cMAY  a3709-37150 v1243 a

Deep eutectic solvents have emerged as inexpensive green alternatives to conventional solvents for diverse applications in chemistry and biology. Despite their importance as useful media in various applications, little is known about the microscopic solvation structures of deep eutectic solvents around solutes. Herein, we show that the electrostatic field, which can be estimated both from infrared experiments and theory, can act as a unified concept to report on the microscopic heterogeneous solvation of deep eutectic solvents. Using a fluorophore containing the carbonyl moiety as the solute and the electrostatic field as a descriptor of the solvation structure of the deep eutectic solvents, we report the residue-specific distribution, orientation, and hydrogen bonding in deep eutectic solvents constituting of choline chloride and alcohols of varying chain-lengths. We observe that an increase in alcohol chain-length not only affects the alcohol's propensity to form hydrogen bond to the solute but also alters the spatial arrangement of choline cations around the solute, thereby leading to a microheterogeneity in the solvation structure. Moreover, to extend our electrostatic field based strategy to other deep eutectic solvents, we report an emission spectroscopy based method. We show that this method can be applied, in general, to all deep eutectic solvents, irrespective of their constituents. Overall, this work integrates experiments with molecular dynamics simulations to provide insights into the heterogeneous DES solvation.

1 aChatterjee, Srijan1 aHaldar, Tapas1 aGhosh, Deborin1 aBagchi, Sayan uhttps://library.ncl.res.in/content/electrostatic-manifestation-micro-heterogeneous-solvation-structures-deep-eutectic-solvents01915nas a2200193 4500008004100000022001400041245010900055210006900164260000800233300001600241490000800257520123200265100001801497700002301515700002201538700001801560700001801578856012501596 2022 eng d a1520-610600aBlue fluorescence of cyano-tryptophan predicts local electrostatics and hydrogen bonding in biomolecules0 aBlue fluorescence of cyanotryptophan predicts local electrostati cDEC a10732-107400 v1263 a

Cyano-tryptophan is an unnatural fluorescent amino acid that emits in the visible region. Along with the structural similarity with tryptophan, the unique photophysical properties of this fluorophore make it an ideal probe for biophysical research. Herein, combining fluorescence spectroscopy, infrared spectroscopy, and molecular dynamics simulations, we show that the cyano-tryptophan's emission energy quantifies the underlying bond-specific noncovalent interactions in terms of the electric field. We further report the use of fluorophore's emission energy to predict its hydrogen bond characteristics. We demonstrate that combining experiments with molecular dynamics simulations can provide the hydrogen bonding status of the nitrile moiety. In addition, we report a method to differentiate between aqueous and nonaqueous hydrogen-bonding partners. Using a phenomenological approach, we demonstrate that the presence of the cyano-indole moiety is responsible for the distinct correlations between the fluorophore's emission and the electrostatic forces on the nitrile bond. As indole is a privileged scaffold for both native amino acids and nucleobases, cyano-indoles will have many multifaceted applications.

1 aHaldar, Tapas1 aChatterjee, Srijan1 aAlam, Md, Nirshad1 aMaity, Pradip1 aBagchi, Sayan uhttps://library.ncl.res.in/content/blue-fluorescence-cyano-tryptophan-predicts-local-electrostatics-and-hydrogen-bonding