8 research outputs found
Energy Managements in the Chemical and Biochemical World, as It may be Understood from the Systems Chemistry Point of View
High Accuracy ab Initio Calculations on Reactions of OH with 1-Alkenes. The Case of Propene
The energetics of terminal, central OH-additions as well as allylic H-abstractions by OH in its reaction with propene was studied as proxies for the 1-alkenes + OH reactions using several single and multireference ab initio techniques with basis set extrapolation where possible. Selection of the localized occupied orbitals forming the active space for multireference methods is discussed. Initial geometries of the reactants, prereaction complex (Ļ-complex), and transition states were determined at the [5,5]-CASPT2/cc-pVTZ level of theory. Frequency analysis was also carried out at this level with the introduction of a scale factor. Analyzing the results, it will be concluded that multireference effects are negligible, and from the various single reference models we will opt for UCCSD(T)/cc-pVTZ for final geometry optimizations and vibrational frequency analysis. These results will be compared with those from approximate models yielding information on the reliability of the latter. Triples contributions are found to be very important, except for the Ļ-complex, which has a UCCSD(T)/CBS relative enthalpy of ā10.56 kJ/mol compared to infinitely separated propene + OH. The addition transition states are found to have relative enthalpies of ā9.93 kJ/mol for the central and ā9.84 kJ/mol for the terminal case. Allylic abstraction mechanisms, although lying significantly higher, still have only slightly positive barriers - a value of 3.21 kJ/mol for the direct and 1.67 kJ/mol for the consecutive case. Conventional transition state theory was used as a rough estimation for determining rate constants and turned out to agree well with experimental data
Computational Elucidation of the Solvent-Dependent Addition of 4āHydroxy-2-nonenal (HNE) to Cysteine and Cysteinate Residues
The lipid peroxidation end product, 4-hydroxy-2-nonenal
(HNE),
is a secondary mediator of oxidative stress due to its strong ability
to form adducts to the side chains of lysine, histidine, and cysteine
residues (Cys) at increasing reactivities. This reaction can take
place in various cellular environments and may be dependent on solvent.
Moreover, approximately 10% of cysteine residues within the cells
exist as the negatively charged cysteinate, which may also have a
distinct reactivity toward HNE. In this study, quantum chemical calculations
are used to investigate the reactivity of HNE toward Cys and cysteinate
in three distinct solvent environments to mimic the aqueous, polar,
and hydrophobic regions within the cell. Water enhances the reactivity
of HNE to cysteine compared to that of the polar and hydrophobic solvents,
and the reactivity of HNE is further augmented when Cys is first ionized
to cysteinate. This is also confirmed by the transition state rate
constant calculations. This study reveals the role of solvent polarity
in these reactions and how cysteinate can account for the seemingly
high reactivity of HNE toward Cys compared to other amino acid residues
and demonstrates how a strong nucleophile can enhance the reactivity
of an antioxidant analogue of the Cys residue
Glutathione as a Prebiotic Answer to Ī±āPeptide Based Life
The
energetics of peptide bond formation is an important factor
not only in the design of chemical peptide synthesis, but it also
has a role in protein biosynthesis. In this work, quantum chemical
calculations at 10 different levels of theory including G3MP2B3 were
performed on the energetics of glutathione formation. The strength
of the peptide bond is found to be closely related to the acid strength
of the to-be N-terminal and the basicity of the to-be C-terminal amino
acid. It is shown that the formation of the first peptide activates
the amino acid for the next condensation step, manifested in bacterial
protein synthesis where the first step is the formation of an N-formylmethionine
dipeptide. The possible role of glutathione in prebiotic molecular
evolution is also analyzed. The implications of the thermodynamics
of peptide bond formation in prebiotic peptide formation as well as
in the preference of Ī±- instead of Ī²- or Ī³-amino
acids are discussed. An empirical correction is proposed for the compensation
of the error due to the incapability of continuum solvation models
in describing the change of the first solvation shell when a peptide
bond is formed from two zwitterions accompanied by the disappearance
of one ion pair
Molecular Dynamics Simulation at High Sodium Chloride Concentration: Toward the Inactive Conformation of the Human Adenosine A2A Receptor
The recently solved crystal structure of the human adenosine A2A receptor (hA2AR) shows the characteristics of a partially activated state. Experimental data suggests that high sodium chloride concentration shifts hA2AR to the inactive state. We found that molecular dynamics simulations at high sodium chloride concentration result in an inactive form of hA2AR reflected in the reformation of the āionic lockā (Arg<sup>102</sup>(3.50)āGlu<sup>228</sup>(6.30)) as well as in the reduction of the Ī±CāĪ±C distance between the intracellular sides of transmembrane helices 3 and 6 (TM3 and TM6). Interestingly, no such stabilization effect was observed at physiological concentrations. Our results suggest that the effect of high sodium chloride concentration might be exploited to generate an inactive state of hA2AR, which is more favorable for identifying pharmacologically relevant antagonists or inverse agonists
Multiscale Modeling of Interfacial Oxidation Mechanism at Air/Organic Interface: Reactions of CH<sub>2</sub>ī»CH-Terminated Self-Assembled Monolayer with OH<sup>ā¢</sup>, O<sub>3</sub>, and HO<sub>2</sub><sup>ā¢</sup>
The
first few elementary steps of the reactions of a structurally
characterized CH<sub>2</sub>ī»CH-terminated self-assembled monolayer
(SAM) with reactive oxygen species, such as OH<sup>ā¢</sup>,
HO<sub>2</sub><sup>ā¢</sup>, and O<sub>3</sub> were investigated
using the multilayer first principle technique (ONIOMĀ[QCISDĀ(T)/cc-pVTZ:MP2/6-311GĀ(d,p):BHandHLYP/6-31GĀ(d)]//ONIOMĀ[BHandHLYP/6-311GĀ(d,p):BHandHLYP/6-31GĀ(d)])
as a proxy for the interfacial oxidation mechanism on organic aerosol
surfaces. The energetics of the reactions is compared with the analogous
QCISDĀ(T)/cc-pVTZ//BHandHLYP/6-311GĀ(d,p) gas-phase results, to measure
the energetic consequences of the presence of the surrounding alkene
chains. All of the reactions studied are affected in such a way that
the relative energies of the interfacial reactions became lower by
the average value of 11.5 Ā± 6.1 kJ/mol than the corresponding
gas-phase values. Because of this effect, interfacial H-abstractions
by OH<sup>ā¢</sup> on both allylic and vinylic positions have
submerged barriers (Ī<i>E</i><sub>0</sub><sup>ā”</sup> = ā5.4 kJ/mol and Ī<i>E</i><sub>0</sub><sup>ā”</sup> = ā5.8 kJ/mol, respectively). Also, the relative
energy of the transition state of the CāC bond scission reaction
started from the nonterminal adduct becoming negative (Ī<i>E</i><sub>0</sub> = ā0.8 kJ/mol). The latter channel
can result in a release of vinyl alcohol and formation of alkyl radical-bearing
SAM. Such lowering of the energy barriers might enhance the overall
oxidation rate and change the branching ratio of the atmospheric oxidation
of the unsaturated compound by OH<sup>ā¢</sup> at the interface
compared to the gas-phase analogues. Because of the importance of
prereaction complexes, the possible orientations of the adsorbed reactive
oxygen species on the surface are also investigated, and OāH
band shifts significantly toward lower wavenumbers in the IR spectra
for the OH<sup>ā¢</sup> and HO<sub>2</sub><sup>ā¢</sup> complexes compared to the gas-phase band, which might be used later
for the detection of these species at the interface if their lifetime
is accessible for such spectroscopy
Atropisomerism of the Asn Ī± Radicals Revealed by Ramachandran Surface Topology
C radicals are typically trigonal
planar and thus achiral, regardless
of whether they originate from a chiral or an achiral C-atom (e.g.,
CāH + <sup>ā¢</sup>OH ā Cā¢ + H<sub>2</sub>O). <b>Oxidative stress</b> could initiate radical formation
in proteins when, for example, the H-atom is abstracted from the CĪ±-carbon
of an amino acid residue. Electronic structure calculations show that
such a radical remains achiral when formed from the achiral Gly, or
the chiral but small Ala residues. However, when longer side-chain
containing proteogenic amino acid residues are studied (e.g., Asn),
they provide radicals of axis chirality, which in turn leads to <b>atropisomerism</b> observed for the first time for peptides. The
two <b>enantiomeric</b> extended backbone <b>structures</b>, ā¢Ī²<sub>L</sub> and ā¢Ī²<sub>D</sub>, interconvert
via a pair of <b>enantiotopic reaction paths</b>, monitored
on a 4D Ramachandran surface, with two distinct transition states
of very different <i>Gibbs</i>-free energies: 37.4 and 67.7
kJ/mol, respectively. This discovery requires the reassessment of
our understanding on radical formation and their conformational and
stereochemical behavior. Furthermore, the atropisomerism of proteogenic
amino acid residues should affect our understanding on radicals in
biological systems and, thus, reframes the role of the D-residues
as markers of <b>molecular aging</b>