A theoretical and matrix-isolation FT-IR investigation of the conformational landscape of N-acetylcysteine

Boeckx, Bram; Ramaekers, Riet; Maes, Guido

doi:10.1016/j.jms.2010.03.007

Cited by 27 publications

(51 citation statements)

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“…This results in a large number of possible conformations and poses a significant challenge in locating true global minima, that is, the most stable conformers. [12] The most stable conformers identified are similar to those reported in ref. [12,29] We carried out a preliminary systematic search by rotating all these internal rotational degrees of freedom involving heavy atoms by either 60 or 1808 sequentially.…”

Section: Neu-nalcsupporting

confidence: 84%

“…The Neu-NALC monomer has seven internal rotational degrees of freedom, [12] which makes it a highly flexible molecule. This results in a large number of possible conformations and poses a significant challenge in locating true global minima, that is, the most stable conformers.…”

Section: Neu-nalcmentioning

confidence: 99%

“…Conformational searches for Neu-NALC have been reported in a number of previous studies. [12], although a larger basis set has been used in the current study. While the work was in progress, an extensive search for Neu-NALC based on a similar approach was reported.…”

Section: Neu-nalcmentioning

confidence: 99%

“…Indeed, much attention has been paid to the properties of NALC from both experimental and theoretical sides. [12] VCD spectroscopy measures the differential absorption of the left versus right circularly polarized IR radiation by a chiral molecule. As a result, NALC exhibits a conformational topology that is frequently found in biological systems.…”

Section: Introductionmentioning

confidence: 99%

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Conformational Distributions of N‐Acetyl‐L‐cysteine in Aqueous Solutions: A Combined Implicit and Explicit Solvation Treatment of VA and VCD Spectra

et al. 2012

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The conformational distributions of N-acetyl-L-cysteine (NALC) in aqueous solutions at several representative pH values are investigated using vibrational absorption (VA), UV/Vis, and vibrational circular dichroism (VCD) spectroscopy, together with DFT and molecular dynamics (MD) simulations. The experimental VA and UV/Vis spectra of NALC in water are obtained under strongly acid, neutral, and strongly basic conditions, as well as the VCD spectrum at pH 7 in D(2)O. Extensive searches are carried out to locate the most stable conformers of the protonated, neutral, deprotonated, and doubly deprotonated NALC species at the B3LYP/6-311++G(d,p) level. The inclusion of the polarizable continuum model (PCM) modifies the geometries and the relative stabilities of the conformers noticeably. The simulated PCM VA spectra show significantly better agreement with the experimental data than the gas-phase ones, thus allowing assignment of the conformational distributions and dominant species under each experimental condition. To further properly account for the discrepancies noted between the experimental and simulated VCD spectra, PCM and the explicit solvent model are utilized. MD simulations are used to aid the modelling of the NALC-(water)(N) clusters. The geometry optimization, harmonic frequency calculations, and VA and VCD intensities are computed for the NALC-(water)(3,4) clusters at the B3LYP/6-311++G(d,p) level without and with the PCM. The inclusion of both explicit and implicit solvation models at the same time provides a decisively better agreement between theory and experiment and therefore conclusive information about the conformational distributions of NALC in water and hydrogen-bonding interactions between NALC and water molecules.

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Section: Neu-nalcsupporting

confidence: 84%

Section: Neu-nalcmentioning

confidence: 99%

Section: Neu-nalcmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Conformational Distributions of N‐Acetyl‐L‐cysteine in Aqueous Solutions: A Combined Implicit and Explicit Solvation Treatment of VA and VCD Spectra

et al. 2012

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“…Since then Gly (Grenie and Garrigou-Lagrange1972;Reva et al 1995;Stepanian et al 1998a;Ivanov et al 1997Ivanov et al , 1999Bazsó et al 2012a, b) and many other amino acids were thoroughly studied by MI-IR spectroscopy, including alanine (Rosado et al 1997;Stepanian et al 1998b;Lambie et al 2003;Bazsó et al 2013), valine (Stepanian et al 1999), leucine (Sheina et al 1988), isoleucine (Boeckx and Maes 2012a), proline (Reva et al 1994;Stepanian et al 2001), serine (Lambie et al 2004;Jarmelo et al 2005;Jarmelo et al 2006), phenylalanine (Kaczor et al 2006), tyrosine (Ramaekers et al 2005), tryptophan (Kaczor et al 2007), cysteine (Dobrowolski et al 2007), asparagine (Boeckx and Maes 2012b), lysine (Boeckx and Maes 2012c), and β-alanine (Rosado et al 1997;Dobrowolski et al 2008). In a step towards understanding the structure and folding of peptides, protected amino acids, the smallest peptide models, were also investigated by this technique, including N-formylglycine (For-Gly, Wierzejewska and OlbertMajkut 2009), N-acetylglycine (Ac-Gly, Boeckx and Maes2012d), N-acetylalanine (Ac-Ala, Boeckx and Maes 2012e), N-acetyproline (Ac-Pro, Boeckx et al 2011), N-acetylcysteine (Ac-Cys, Boeckx et al 2010), Nacetyl-N′-methyl-glycine-amide (Ac-Gly-NHMe, Grenie et al1975;Pohl et al 2007), N-acetyl-N′-methyl-Lalanine-amide (Ac-L-Ala-NHMe, Grenie et al 1975;Pohl et al2007), and their water complexes Pohl et al 2008)…”

Section: Introductionmentioning

confidence: 99%

Foldamers of β-peptides: conformational preference of peptides formed by rigid building blocks. The first MI-IR spectra of a triamide nanosystem

et al. 2013

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IntroductionAlthough dynamic on a large timescale of motion, some biologically active polyamide nanosystems adopt welldefined 3D structures in a time average manner, called as globular proteins; a given name reflecting to their overall shape. Other proteins called intrinsically unstructured or dynamic (IUP or IDP) are reluctant to present such an easy to characterize structural ensemble, nicknamed as proteins with random structures. Thus, proteins exist in most phases as conformational ensembles presenting lower, while in other environment higher time average deviation from their average 3D folds. The α-amino acid sequence modification of these inherently dynamic polyamide systems can lower, or increase the amplitude and frequency of such internal motion, making the protein fold less or more -mobile‖. The chemical constitution (α) and the stereochemistry (L) of proteogenic amino acid residues are under strict evolutional conservation. Unlike L-Proline, all the remaining 19 common residues in proteins have two adjacent backbone torsional angles, φ and ψ, of high rotational freedom followed by the inflexible ω. The scenario of two flexible followed by a fixed backbone torsional angles per residue determines primarily the folding ability of a proteogenic polypeptide. Cutting of a globular fold seldom results in secondary structural elements (e.g. α-helix, β-turn) of low internal dynamics! Typically the removal of any secondary structural element from its -natural environment‖ results in polypetides of very elevated internal dynamics, often characterized as unstructured subunits. However, bioengineering requires stable toolkits to design epitopes, matching complementary folds, individual foldamers, nano-lego elements etc. of traceable shape and of low internal mobility. Shedding light on folding and stability of secondary structural elements of peptides and proteins could help to design standalone foldamers. They could be composed of β-, α-and α/β-amino acid residues, the latter called chimera. A general expectation of foldamers is to present a single time average 3D-structure of lower internal dynamics over the large timescale of picoseconds to second. These fold optimized biocompatible and nonnatural peptides often have an increased proteolytic and metabolic stability and can fulfill diverse biological functions toward DNA, RNA, ATP, etc. The improved ability of β-peptides and thus β-foldamers to rapidly and spontaneously fold (

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Impact of the Acetyl Group on Cysteine: A Study of N‐Acetyl‐Cysteine through Rotational Spectroscopy

Mato,

Municio,

Alonso

et al. 2024

ChemPhysChem

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Herein, we report a spectroscopic study of N‐acetyl‐L‐cysteine, an important antioxidant drug, using Fourier‐transform microwave techniques and in isolated conditions. Two conformers are observed, where most stable structure adopts a cis disposition, and the second conformer has a lower abundance and adopts a trans disposition. The rotational constants and the barriers to methyl internal rotation are determined for each conformer, allowing a precise conformation identification. The results show that the cis form adopts an identical structure in the crystal, solution, and gas phases. Additionally, the structures are contrasted against those of cysteine

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A theoretical and matrix-isolation FT-IR investigation of the conformational landscape of N-acetylcysteine

Cited by 27 publications

References 50 publications

Conformational Distributions of N‐Acetyl‐L‐cysteine in Aqueous Solutions: A Combined Implicit and Explicit Solvation Treatment of VA and VCD Spectra

Conformational Distributions of N‐Acetyl‐L‐cysteine in Aqueous Solutions: A Combined Implicit and Explicit Solvation Treatment of VA and VCD Spectra

Foldamers of β-peptides: conformational preference of peptides formed by rigid building blocks. The first MI-IR spectra of a triamide nanosystem

Impact of the Acetyl Group on Cysteine: A Study of N‐Acetyl‐Cysteine through Rotational Spectroscopy

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