9 research outputs found
Experimental Determination of the Electrostatic Nature of Carbonyl Hydrogen-Bonding Interactions Using IR-NMR Correlations
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–<sup>13</sup>C 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
Cosolvent Effects on Solute-Solvent Hydrogen-Bond Dynamics: Ultrafast 2D IR Investigations
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.close0
Two-Dimensional Infrared Spectroscopy Reveals Cosolvent-Composition-Dependent Crossover in Intermolecular Hydrogen-Bond Dynamics
Cosolvents 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 two-dimensional infrared spectroscopy experiments. Our results demonstrate the cosolvent-concentration-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.clos
Effect of DMSO as a Cosolvent on Carbonyl Hydrogen-Bond Dynamics in Aqueous Solution is revealed by 2D IR
Arresting an Unusual Amide Tautomer Using Divalent Cations
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
Pick and Choose the Spectroscopic Method to Calibrate the Local Electric Field inside Proteins
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 <sup>13</sup>C 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
Correlating Nitrile IR Frequencies to Local Electrostatics Quantifies Noncovalent Interactions of Peptides and Proteins
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
Proceedings of National Conference on Relevance of Engineering and Science for Environment and Society
This conference proceedings contains articles on the various research ideas of the academic community and practitioners presented at the National Conference on Relevance of Engineering and Science for Environment and Society (R{ES}2 2021). R{ES}2 2021 was organized by Shri Pandurang Pratishthan’s, Karmayogi Engineering College, Shelve, Pandharpur, India on July 25th, 2021.
Conference Title: National Conference on Relevance of Engineering and Science for Environment and SocietyConference Acronym: R{ES}2 2021Conference Date: 25 July 2021Conference Location: Online (Virtual Mode)Conference Organizers: Shri Pandurang Pratishthan’s, Karmayogi Engineering College, Shelve, Pandharpur, India