Mironel Enescu - Academia.edu (original) (raw)
Papers by Mironel Enescu
The Journal of Physical Chemistry B, Mar 4, 2010
Free energy profiles were calculated for the reduction of the four disulfide bridges in lysozyme ... more Free energy profiles were calculated for the reduction of the four disulfide bridges in lysozyme by tris(2-carboxyethyl)phosphine (TCEP). The computational method combines high-precision density functional theory (DFT) calculations performed on the core of the reactant system with classical mechanical free energy evaluations based on the sampling of the configuration space of reaction environment. The predicted reaction energy barriers are in satisfactory agreement with experimental data, proving that the present method provides a reliable description of the mechanism of reaction. The role of the protein environment in this mechanism is further emphasized by analyzing the different contributions to the free energy profiles. It is shown that the protein environment affects the reaction by three factors: polarizability, steric hindrance of the reactant site, and S-S bridge distortion due to structural constraints. The corresponding effects are quantitatively evaluated, and the results are discussed in connection with the current two-step reaction model for the reduction of S-S bridges in proteins.
Inorganic chemistry, Jan 21, 2015
We present results obtained from high energy-resolution L3-edge XANES spectroscopy and first-prin... more We present results obtained from high energy-resolution L3-edge XANES spectroscopy and first-principles calculations for the structure, bonding, and stability of mercury(II) complexes with thiolate and thioether ligands in crystalline compounds, aqueous solution, and macromolecular natural organic matter (NOM). Core-to-valence XANES features that vary in intensity differentiate with unprecedented sensitivity the number and identity of Hg ligands and the geometry of the ligand environment. Post-Hartree-Fock XANES calculations, coupled with natural population analysis, performed on MP2-optimized Hg[(SR)2···(RSR)n] complexes show that the shape, position, and number of electronic transitions observed at high energy-resolution are directly correlated to the Hg and S (l,m)-projected empty densities of states and occupations of the hybridized Hg 6s and 5d valence orbitals. Linear two-coordination, the most common coordination geometry in mercury chemistry, yields a sharp 2p to 6s + 5d ele...
The Journal of Physical Chemistry, 1995
ABSTRACT
Journal of Molecular Modeling, 2015
Parameterization of molecular complexes containing a metallic compound, such as cisplatin, is cha... more Parameterization of molecular complexes containing a metallic compound, such as cisplatin, is challenging due to the unconventional coordination nature of the bonds which involve platinum atoms. In this work, we develop a new methodology of parameterization for such compounds based on quantum dynamics (QD) calculations. We show that the coordination bonds and angles are more flexible than in normal covalent compounds. The influence of explicit solvent is also shown to be crucial to determine the flexibility of cisplatin in quantum dynamics simulations. Two empirical topologies of cisplatin were produced by fitting its atomic fluctuations against QD in vacuum and QD with explicit first solvation shell of water molecules respectively. A third topology built in a standard way from the static optimized structure was used for comparison. The later one leads to an excessively rigid molecule and exhibits much smaller fluctuations of the bonds and angles than QD reveals. It is shown that accounting for the high flexibility of cisplatin molecule is needed for adequate description of its first hydration shell. MD simulations with flexible QD-based topology also reveal a significant decrease of the barrier of passive diffusion of cisplatin accross the model lipid bilayer. These results confirm that flexibility of organometallic compounds is an important feature to be considered in classical molecular dynamics topologies. Proposed methodology based on QD simulations provides a systematic way of building such topologies.
Proceedings of SPIE - The International Society for Optical Engineering
The Journal of Physical Chemistry, 1995
ABSTRACT
Environmental science & technology, Jan 13, 2015
Methylmercury is the environmental form of neurotoxic mercury that is biomagnified in the food ch... more Methylmercury is the environmental form of neurotoxic mercury that is biomagnified in the food chain. Methylation rates are reduced when the metal is sequestered in crystalline mercury sulfides or bound to thiol groups in macromolecular natural organic matter. Mercury sulfide minerals are known to nucleate in anoxic zones, by reaction of the thiol-bound mercury with biogenic sulfide, but not in oxic environments. We present experimental evidence that mercury sulfide forms from thiol-bound mercury alone in aqueous dark systems in contact with air. The maximum amount of nanoparticulate mercury sulfide relative to thiol-bound mercury obtained by reacting dissolved mercury and soil organic matter matches that detected in the organic horizon of a contaminated soil situated downstream from Oak Ridge, Tennessee, in the USA. The nearly identical ratios of the two forms of mercury in field and experimental systems suggest a common reaction mechanism for nucleating the mineral. We identified ...
Journal of molecular modeling, 2015
The unfolding of the reduced human serum albumin (HSA) was simulated by generating four molecular... more The unfolding of the reduced human serum albumin (HSA) was simulated by generating four molecular dynamics (MD) trajectories of 160 ns each at 350, 375, 400, and 425 K, respectively. A principal components analysis (PCA) was performed on the four trajectories. Based on this analysis, 17 representative protein conformers were identified and subsequently used to construct a sequence of partially unfolded structures. They were ordered according to their decreasing α-helix fractions. The structural evolution in this unfolding sequence was found to be continuous at global but also at local level supporting the hypothesis that the protein unfolding pathway is not significantly dependent on the simulation temperature. As a result, the α-helix fraction of the protein appears to be a good reaction coordinate for the unfolding process, as it was previously suggested by experiments. Based on this observation, two conformers in the unfolding sequence were predicted to be close to the equilibriu...
Vibrational Spectroscopy, 2007
The Raman spectrum of the 1:2 zinc-cysteine complex in aqueous solution is compared to those of c... more The Raman spectrum of the 1:2 zinc-cysteine complex in aqueous solution is compared to those of cysteine zwitterion and cysteine anion in order to identify specific complexation effects. Band assignment is based on frequency calculation and normal modes analysis using the density functional theory (DFT) method. Two bands specific to the complex were detected in the 200-400 cm À1 spectral range. It is shown that the corresponding vibrations are not pure metal-ligand modes but that they result from the coupling between the Zn-S and Zn-N stretching modes with some cysteine internal modes. Raman spectra analysis also provides direct evidence for the deprotonation of the SH and NH 3 + groups of cysteine upon zinc binding. It is found in addition that complexation significantly affects the cysteine internal mode mixing in the 500-1500 cm À1 spectral range. The results are considered in connection with the spectral characterization of zinc-protein complexes of biological interest. #
ROMOPTO 2000: Sixth Conference on Optics, 2001
ABSTRACT
The disulfide bridges have a crucial role in the stability of native protein structures. The stud... more The disulfide bridges have a crucial role in the stability of native protein structures. The study of the mechanism of their reduction in biological environment is very important in order to understand their functions [1]. The aim of our study was to analyze the role that protein ...
Laser Florence 2000: A Window on the Laser Medicine World, 2001
ABSTRACT
Trends in Quantum Electronics, 1989
ABSTRACT The emission of a transversely pumped dye laser using the rate equation approximation is... more ABSTRACT The emission of a transversely pumped dye laser using the rate equation approximation is described considering both the laser and the amplified spontaneous emission (A.S.E.) modes, when a pulsed pumping laser is used. The computed results are in good agreement with the experimental data when the real spatial distribution of pumping energy is considered. A N2-laser pumped tunable dye laser useful for low concentrations measurements of complex mole-cules in solutions is described.
Le Journal de Physique Colloques, 1987
Journal of Fluorescence, 2000
We report on the application of fluorescence correlation microscopy under two-photon excitation o... more We report on the application of fluorescence correlation microscopy under two-photon excitation of fluorophores of biological interest: FITC–dextran (MW, from 20 to 150 kDa), green fluorescent protein (MW, 27 kDa), and fluorescein (MW, 330 Da). Under these experimental conditions, the translational diffusion coefficients of these molecules in aqueous solutions derived from the fluorescence intensity autocorrelation function were determined for the
Theoretical Chemistry Accounts, 2014
ABSTRACT The reliability of ab initio methods to predict accurate thermodynamic properties and co... more ABSTRACT The reliability of ab initio methods to predict accurate thermodynamic properties and coordination geometries of mercury–thiolate complexes was examined with calculations at various levels of theory. The second-order Møller–Plesset perturbation theory (MP2) method in connection with the Stuttgart–Dresden–Bonn relativistic effective core potentials and the related correlation consistent valence basis set gives optimized Hg(RS) n model structures in good agreement with experimental data. Differences in thermodynamic stability among various models can be estimated with chemical precision using single-point energy calculation at the CCSD(T) level of theory performed on the MP2-optimized structures. This computational scheme was applied next to calculate the stability of aqueous linear (two coordinated), trigonal, and tetrahedral mercury–thiolate complexes. In alkaline solutions, the difference in complexation Gibbs free energy between the most stable (trigonal) and the less stable (tetrahedral) model complexes formed with free ligands is only −4.7 kcal mol−1. At neutral pH, the linear coordination is most stable. When the thiol ligands are structurally associated, as in biological systems, the trigonal coordination is most stable from pH 4.8 to 10.6. The relative stabilities of the three Hg–(RS) n bonding configurations reported herein can be further modified in biological environment by Hg-induced folding of proteins.
The Journal of Physical Chemistry B, 2010
Free energy profiles were calculated for the reduction of the four disulfide bridges in lysozyme ... more Free energy profiles were calculated for the reduction of the four disulfide bridges in lysozyme by tris(2-carboxyethyl)phosphine (TCEP). The computational method combines high-precision density functional theory (DFT) calculations performed on the core of the reactant system with classical mechanical free energy evaluations based on the sampling of the configuration space of reaction environment. The predicted reaction energy barriers are in satisfactory agreement with experimental data, proving that the present method provides a reliable description of the mechanism of reaction. The role of the protein environment in this mechanism is further emphasized by analyzing the different contributions to the free energy profiles. It is shown that the protein environment affects the reaction by three factors: polarizability, steric hindrance of the reactant site, and S-S bridge distortion due to structural constraints. The corresponding effects are quantitatively evaluated, and the results are discussed in connection with the current two-step reaction model for the reduction of S-S bridges in proteins.
The Journal of Physical Chemistry A, 2007
In spite of the large quantity of experimental work that deals with the oxidation of thiols by su... more In spite of the large quantity of experimental work that deals with the oxidation of thiols by superoxide, the mechanism of this reaction is still controversial. The ab initio molecular orbital calculations reported here predict that the main reaction pathway includes the formation of a three-electron-bonded adduct followed by the elimination of the hydroxide anion, giving the sulfinyl radical as the reaction product. The alternative reaction pathway consisting of hydrogen atom transfer from the thiol to the protonated superoxide radical involves a reaction energy barrier that is significantly higher. The difference between the two reaction energy barriers is clearly beyond the expected computational uncertainty. The systematic scanning of the potential energy surface reveals no other competitive reaction pathways. The present results provide a useful basis for the interpretation of the complex experimental data related to thiol oxidation by superoxide radical in a biological environment.
Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, 2014
The Journal of Physical Chemistry B, Mar 4, 2010
Free energy profiles were calculated for the reduction of the four disulfide bridges in lysozyme ... more Free energy profiles were calculated for the reduction of the four disulfide bridges in lysozyme by tris(2-carboxyethyl)phosphine (TCEP). The computational method combines high-precision density functional theory (DFT) calculations performed on the core of the reactant system with classical mechanical free energy evaluations based on the sampling of the configuration space of reaction environment. The predicted reaction energy barriers are in satisfactory agreement with experimental data, proving that the present method provides a reliable description of the mechanism of reaction. The role of the protein environment in this mechanism is further emphasized by analyzing the different contributions to the free energy profiles. It is shown that the protein environment affects the reaction by three factors: polarizability, steric hindrance of the reactant site, and S-S bridge distortion due to structural constraints. The corresponding effects are quantitatively evaluated, and the results are discussed in connection with the current two-step reaction model for the reduction of S-S bridges in proteins.
Inorganic chemistry, Jan 21, 2015
We present results obtained from high energy-resolution L3-edge XANES spectroscopy and first-prin... more We present results obtained from high energy-resolution L3-edge XANES spectroscopy and first-principles calculations for the structure, bonding, and stability of mercury(II) complexes with thiolate and thioether ligands in crystalline compounds, aqueous solution, and macromolecular natural organic matter (NOM). Core-to-valence XANES features that vary in intensity differentiate with unprecedented sensitivity the number and identity of Hg ligands and the geometry of the ligand environment. Post-Hartree-Fock XANES calculations, coupled with natural population analysis, performed on MP2-optimized Hg[(SR)2···(RSR)n] complexes show that the shape, position, and number of electronic transitions observed at high energy-resolution are directly correlated to the Hg and S (l,m)-projected empty densities of states and occupations of the hybridized Hg 6s and 5d valence orbitals. Linear two-coordination, the most common coordination geometry in mercury chemistry, yields a sharp 2p to 6s + 5d ele...
The Journal of Physical Chemistry, 1995
ABSTRACT
Journal of Molecular Modeling, 2015
Parameterization of molecular complexes containing a metallic compound, such as cisplatin, is cha... more Parameterization of molecular complexes containing a metallic compound, such as cisplatin, is challenging due to the unconventional coordination nature of the bonds which involve platinum atoms. In this work, we develop a new methodology of parameterization for such compounds based on quantum dynamics (QD) calculations. We show that the coordination bonds and angles are more flexible than in normal covalent compounds. The influence of explicit solvent is also shown to be crucial to determine the flexibility of cisplatin in quantum dynamics simulations. Two empirical topologies of cisplatin were produced by fitting its atomic fluctuations against QD in vacuum and QD with explicit first solvation shell of water molecules respectively. A third topology built in a standard way from the static optimized structure was used for comparison. The later one leads to an excessively rigid molecule and exhibits much smaller fluctuations of the bonds and angles than QD reveals. It is shown that accounting for the high flexibility of cisplatin molecule is needed for adequate description of its first hydration shell. MD simulations with flexible QD-based topology also reveal a significant decrease of the barrier of passive diffusion of cisplatin accross the model lipid bilayer. These results confirm that flexibility of organometallic compounds is an important feature to be considered in classical molecular dynamics topologies. Proposed methodology based on QD simulations provides a systematic way of building such topologies.
Proceedings of SPIE - The International Society for Optical Engineering
The Journal of Physical Chemistry, 1995
ABSTRACT
Environmental science & technology, Jan 13, 2015
Methylmercury is the environmental form of neurotoxic mercury that is biomagnified in the food ch... more Methylmercury is the environmental form of neurotoxic mercury that is biomagnified in the food chain. Methylation rates are reduced when the metal is sequestered in crystalline mercury sulfides or bound to thiol groups in macromolecular natural organic matter. Mercury sulfide minerals are known to nucleate in anoxic zones, by reaction of the thiol-bound mercury with biogenic sulfide, but not in oxic environments. We present experimental evidence that mercury sulfide forms from thiol-bound mercury alone in aqueous dark systems in contact with air. The maximum amount of nanoparticulate mercury sulfide relative to thiol-bound mercury obtained by reacting dissolved mercury and soil organic matter matches that detected in the organic horizon of a contaminated soil situated downstream from Oak Ridge, Tennessee, in the USA. The nearly identical ratios of the two forms of mercury in field and experimental systems suggest a common reaction mechanism for nucleating the mineral. We identified ...
Journal of molecular modeling, 2015
The unfolding of the reduced human serum albumin (HSA) was simulated by generating four molecular... more The unfolding of the reduced human serum albumin (HSA) was simulated by generating four molecular dynamics (MD) trajectories of 160 ns each at 350, 375, 400, and 425 K, respectively. A principal components analysis (PCA) was performed on the four trajectories. Based on this analysis, 17 representative protein conformers were identified and subsequently used to construct a sequence of partially unfolded structures. They were ordered according to their decreasing α-helix fractions. The structural evolution in this unfolding sequence was found to be continuous at global but also at local level supporting the hypothesis that the protein unfolding pathway is not significantly dependent on the simulation temperature. As a result, the α-helix fraction of the protein appears to be a good reaction coordinate for the unfolding process, as it was previously suggested by experiments. Based on this observation, two conformers in the unfolding sequence were predicted to be close to the equilibriu...
Vibrational Spectroscopy, 2007
The Raman spectrum of the 1:2 zinc-cysteine complex in aqueous solution is compared to those of c... more The Raman spectrum of the 1:2 zinc-cysteine complex in aqueous solution is compared to those of cysteine zwitterion and cysteine anion in order to identify specific complexation effects. Band assignment is based on frequency calculation and normal modes analysis using the density functional theory (DFT) method. Two bands specific to the complex were detected in the 200-400 cm À1 spectral range. It is shown that the corresponding vibrations are not pure metal-ligand modes but that they result from the coupling between the Zn-S and Zn-N stretching modes with some cysteine internal modes. Raman spectra analysis also provides direct evidence for the deprotonation of the SH and NH 3 + groups of cysteine upon zinc binding. It is found in addition that complexation significantly affects the cysteine internal mode mixing in the 500-1500 cm À1 spectral range. The results are considered in connection with the spectral characterization of zinc-protein complexes of biological interest. #
ROMOPTO 2000: Sixth Conference on Optics, 2001
ABSTRACT
The disulfide bridges have a crucial role in the stability of native protein structures. The stud... more The disulfide bridges have a crucial role in the stability of native protein structures. The study of the mechanism of their reduction in biological environment is very important in order to understand their functions [1]. The aim of our study was to analyze the role that protein ...
Laser Florence 2000: A Window on the Laser Medicine World, 2001
ABSTRACT
Trends in Quantum Electronics, 1989
ABSTRACT The emission of a transversely pumped dye laser using the rate equation approximation is... more ABSTRACT The emission of a transversely pumped dye laser using the rate equation approximation is described considering both the laser and the amplified spontaneous emission (A.S.E.) modes, when a pulsed pumping laser is used. The computed results are in good agreement with the experimental data when the real spatial distribution of pumping energy is considered. A N2-laser pumped tunable dye laser useful for low concentrations measurements of complex mole-cules in solutions is described.
Le Journal de Physique Colloques, 1987
Journal of Fluorescence, 2000
We report on the application of fluorescence correlation microscopy under two-photon excitation o... more We report on the application of fluorescence correlation microscopy under two-photon excitation of fluorophores of biological interest: FITC–dextran (MW, from 20 to 150 kDa), green fluorescent protein (MW, 27 kDa), and fluorescein (MW, 330 Da). Under these experimental conditions, the translational diffusion coefficients of these molecules in aqueous solutions derived from the fluorescence intensity autocorrelation function were determined for the
Theoretical Chemistry Accounts, 2014
ABSTRACT The reliability of ab initio methods to predict accurate thermodynamic properties and co... more ABSTRACT The reliability of ab initio methods to predict accurate thermodynamic properties and coordination geometries of mercury–thiolate complexes was examined with calculations at various levels of theory. The second-order Møller–Plesset perturbation theory (MP2) method in connection with the Stuttgart–Dresden–Bonn relativistic effective core potentials and the related correlation consistent valence basis set gives optimized Hg(RS) n model structures in good agreement with experimental data. Differences in thermodynamic stability among various models can be estimated with chemical precision using single-point energy calculation at the CCSD(T) level of theory performed on the MP2-optimized structures. This computational scheme was applied next to calculate the stability of aqueous linear (two coordinated), trigonal, and tetrahedral mercury–thiolate complexes. In alkaline solutions, the difference in complexation Gibbs free energy between the most stable (trigonal) and the less stable (tetrahedral) model complexes formed with free ligands is only −4.7 kcal mol−1. At neutral pH, the linear coordination is most stable. When the thiol ligands are structurally associated, as in biological systems, the trigonal coordination is most stable from pH 4.8 to 10.6. The relative stabilities of the three Hg–(RS) n bonding configurations reported herein can be further modified in biological environment by Hg-induced folding of proteins.
The Journal of Physical Chemistry B, 2010
Free energy profiles were calculated for the reduction of the four disulfide bridges in lysozyme ... more Free energy profiles were calculated for the reduction of the four disulfide bridges in lysozyme by tris(2-carboxyethyl)phosphine (TCEP). The computational method combines high-precision density functional theory (DFT) calculations performed on the core of the reactant system with classical mechanical free energy evaluations based on the sampling of the configuration space of reaction environment. The predicted reaction energy barriers are in satisfactory agreement with experimental data, proving that the present method provides a reliable description of the mechanism of reaction. The role of the protein environment in this mechanism is further emphasized by analyzing the different contributions to the free energy profiles. It is shown that the protein environment affects the reaction by three factors: polarizability, steric hindrance of the reactant site, and S-S bridge distortion due to structural constraints. The corresponding effects are quantitatively evaluated, and the results are discussed in connection with the current two-step reaction model for the reduction of S-S bridges in proteins.
The Journal of Physical Chemistry A, 2007
In spite of the large quantity of experimental work that deals with the oxidation of thiols by su... more In spite of the large quantity of experimental work that deals with the oxidation of thiols by superoxide, the mechanism of this reaction is still controversial. The ab initio molecular orbital calculations reported here predict that the main reaction pathway includes the formation of a three-electron-bonded adduct followed by the elimination of the hydroxide anion, giving the sulfinyl radical as the reaction product. The alternative reaction pathway consisting of hydrogen atom transfer from the thiol to the protonated superoxide radical involves a reaction energy barrier that is significantly higher. The difference between the two reaction energy barriers is clearly beyond the expected computational uncertainty. The systematic scanning of the potential energy surface reveals no other competitive reaction pathways. The present results provide a useful basis for the interpretation of the complex experimental data related to thiol oxidation by superoxide radical in a biological environment.
Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, 2014