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1.
Environ Sci Process Impacts ; 23(10): 1600-1611, 2021 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-34596189

RESUMO

In vitro and in vivo experimental models, mainly based on cell cultures, animals, healthy humans and clinical trials, are useful approaches for identifying the main metabolic pathways. However, time, cost, and matrix complexity often hinder the success of these methods. In this study, we propose an alternative non-enzymatic method, using electrochemistry (EC) coupled to liquid chromatography (LC) - high resolution mass spectrometry (HRMS) - DFT theoretical calculations (EC/LC-MS/DFT) for the mimicry/simulation of the environmental degradation of phenylurea herbicides, and for the mechanism elucidation of this class of herbicides. Fenuron, monuron, isoproturon, linuron, monolinuron, metoxuron and chlortoluron were selected as relevant model compounds. The intended compounds are oxidized by EC, separated by LC and detected using electrospray ionization HRMS. The main oxidation products were hydroxylated compounds obtained by substitution and addition reactions. Unstable quinone imines/methines, rarely observed by conventional methods, have been identified during the oxidative degradation of phenylurea herbicides for the first time in this study. Some were directly observed and the others were trapped by glutathione GSH. Reactions such as hydrolytic substitutions (-Cl/+OH and -C3H7/+OH and -CH3/+OH and -OCH3/+OH), aromatic hydroxylation, alkyl carbon hydroxylation, dehydrochlorination/dehydromethylation/dehydromethoxylation and conjugation have been successfully mimicked. The obtained results, supported by theoretical calculations, are useful for simulating/understanding and predicting the oxidative degradation pathways of pesticides in the environment.


Assuntos
Herbicidas , Animais , Cromatografia Líquida , Teoria da Densidade Funcional , Eletroquímica , Herbicidas/análise , Humanos , Compostos de Fenilureia/análise , Espectrometria de Massas por Ionização por Electrospray
2.
J Mol Model ; 27(11): 323, 2021 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-34643800

RESUMO

The world has face the COVID-19 pandemic which has already caused millions of death. Due to the urgency in fighting the virus, we study five residues of free amino acids present in the structure of the SARS-CoV-2 spike protein (S). We investigated the spontaneous interaction between amino acids and silver ions (Ag+), considering these ions as a virucide chemical agent for SARS-CoV-2. The amino acid-Ag+ systems were investigated in a gaseous medium and a simulated water environment was described with a continuum model (PCM) the calculations were performed within the framework of density functional theory (DFT). Calculations related to the occupied orbitals of higher energy showed that Ag+ has a tendency to interact with the nitrile groups (-NH). The negative values of the Gibbs free energies show that the interaction process between amino acids-Ag+ in both media occurs spontaneously. There is a decrease in Gibbs free energy from the amino acid-Ag+ interactions immersed in a water solvation simulator.


Assuntos
Aminoácidos/química , Antivirais/química , Teoria da Densidade Funcional , Prata/química , Glicoproteína da Espícula de Coronavírus/química , Aminoácidos/metabolismo , Antivirais/metabolismo , Sítios de Ligação , Cátions Monovalentes , Expressão Gênica , Humanos , Ligação Proteica , Conformação Proteica em alfa-Hélice , Conformação Proteica em Folha beta , Domínios e Motivos de Interação entre Proteínas , SARS-CoV-2/química , Prata/metabolismo , Glicoproteína da Espícula de Coronavírus/antagonistas & inibidores , Glicoproteína da Espícula de Coronavírus/genética , Glicoproteína da Espícula de Coronavírus/metabolismo , Eletricidade Estática , Termodinâmica
3.
Phys Chem Chem Phys ; 23(34): 19043-19053, 2021 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-34612442

RESUMO

Reaction pathway of prebiotic reactions for formation of the pteridines: pterin, xanthopterine, isoxanthopterine and leucopterine, as well as the purine nucleobase guanine from pure formamide are presented. In these reactions, formamide or its tautomer, formimidic acid, play the role of proton-carrying catalyst. All required raw materials, such as hydrogen cyanide, ammonia, water, formic acid, urea, 2-aminomalononitrile, glyoxal, glyoxylic acid and oxalic acid needed in the self-catalyzed reactions are obtained by partial decomposition of formamide. We show that the prebiotic formation of nucleobases and pterins is closely linked and they probably coexisted at the beginning of chemical evolution.


Assuntos
Formamidas/química , Guanina/síntese química , Prebióticos , Pterinas/síntese química , Catálise , Teoria da Densidade Funcional , Evolução Química , Guanina/química , Pterinas/química , Temperatura
4.
Phys Chem Chem Phys ; 23(37): 21148-21162, 2021 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-34528029

RESUMO

The early mechanisms by which ionizing rays damage biological structures by so-called direct effects are largely elusive. In a recent picosecond pulse radiolysis study of concentrated uridine monophosphate solutions [J. Ma, S. A. Denisov, J.-L. Marignier, P. Pernot, A. Adhikary, S. Seki and M. Mostafavi, J. Phys. Chem. Lett., 2018, 9, 5105], unexpected results were found regarding the oxidation of the nucleobase. The signature of the oxidized nucleobase could not be detected 5 ps after the electron pulse, but only the oxidized phosphate, raising intriguing questions about the identity of charge-transfer mechanisms that could explain the absence of U+. We address here this question by means of advanced first-principles atomistic simulations of solvated uridine monophosphate, combining Density Functional Theory (DFT) with polarizable embedding schemes. We contrast three very distinct mechanisms of charge transfer covering the atto-, femto- and pico-second timescales. We first investigate the ionization mechanism and subsequent hole/charge migrations on a timescale of attoseconds to a few femtoseconds under the frozen nuclei approximation. We then consider a nuclear-driven phosphate-to-oxidized-nucleobase electron transfer, showing that it is an uncompetitive reaction channel on the sub-picosecond timescale, despite its high exothermicity and significant electronic coupling. Finally, we show that non-adiabatic charge transfer is enabled by femtosecond nuclear relaxation after ionization. We show that electronic decoherence and the electronic coupling strength are the key parameters that determine the hopping probabilities. Our results provide important insight into the interplay between electronics and nuclear motions in the early stages of the multiscale responses of biological matter subjected to ionizing radiation.


Assuntos
Uridina Monofosfato/química , Água/química , Teoria da Densidade Funcional , Transporte de Elétrons , Hélio/química , Íons/química , Simulação de Dinâmica Molecular , Uridina Monofosfato/metabolismo
5.
Phys Chem Chem Phys ; 23(37): 21130-21138, 2021 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-34528038

RESUMO

As global warming due to CO2 emissions has become a widely recognized concern, CO2 capture, sequestration, neutralization, and conversion have become possible solutions to address this concern. Among these approaches, the conversion of CO2 into fuels or value-added products has attracted considerable attention. In this work, we report the high-efficiency conversion of CO2 to important industrial raw materials for pharmaceutical compounds, quinazoline-2,4(1H,3H)-diones, via reactions with 2-aminobenzonitriles at room temperature and under ambient pressure, with high conversion yields (91.5-99.3%). 1,8-Diazabicyclo-[5.4.0]-undec-7-ene (DBU), 1,1,3,3-tetramethylguanidine (TMG), and cholinium (Ch) ammonium-based ionic liquids (ILs) are employed as catalysts during the process. Cations with a pKa value near 11.9 and anions with a pKa value range of 10 to 15 are necessary for the reaction. The experimental results indicate that the ionic liquid pair [HDBU+][3-Cl-PhO-] has high efficiency under very mild conditions, obtaining high product yields of 91.5% at 25 °C and 1 atm and 99.3% at 30 °C and 1 atm. More importantly, the catalysts retain high efficiency and activity after 5 consecutive cycles. To gain insightful understanding of the reaction, density functional theory (DFT) calculations were conducted to study the reaction mechanism. The computational results indicate that the catalytic process contains three stages: cyano activation, intramolecular rearrangement, and intramolecular cyclization. Of these, the rate-determining step is cyano activation, which shows an energy barrier of 24.5 kcal mol-1. Tuning the types of ions in ILs can effectively reduce this energy barrier and allow high efficiencies.


Assuntos
Dióxido de Carbono/química , Quinazolinas/química , Compostos Bicíclicos Heterocíclicos com Pontes/síntese química , Compostos Bicíclicos Heterocíclicos com Pontes/química , Catálise , Ciclização , Teoria da Densidade Funcional , Guanidinas/síntese química , Guanidinas/química , Líquidos Iônicos/síntese química , Líquidos Iônicos/química , Nitrilas/química , Pressão , Quinazolinas/síntese química , Temperatura
6.
Phys Chem Chem Phys ; 23(37): 21207-21217, 2021 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-34533552

RESUMO

We investigate the interaction between the programmed cell death protein 1 (PD-1) and the programmed cell death ligand 1 (PD-L1), as well as the immuno-oncological drugs pembrolizumab (PEM), and nivolumab (NIV), through quantum chemistry methods based on the Density Functional Theory (DFT) and the molecular fractionation with conjugate caps (MFCC) scheme, in order to map their hot-spot regions. Our results showed that the total interaction energy order of the three complexes is in good agreement with the experimental binding affinity order: PD-1/PEM > PD-1/NIV > PD-1/PD-L1. Besides, a detailed investigation revealed the energetically most relevant residue-residue pairs-interaction for each complex. Our computational results give a better understanding of the interaction mechanism between the protein PD-1 and its ligands (natural and inhibitors), unleashing the immune surveillance to destroy the cancer cells by decreasing their immune evasion. They are also an efficient alternative towards the development of new small-molecules and antibody-based drugs, pointing out to new treatments for cancer therapy.


Assuntos
Anticorpos Monoclonais Humanizados/imunologia , Antígeno B7-H1/metabolismo , Nivolumabe/imunologia , Receptor de Morte Celular Programada 1/metabolismo , Antígeno B7-H1/química , Teoria da Densidade Funcional , Humanos , Ligantes , Receptor de Morte Celular Programada 1/química , Receptor de Morte Celular Programada 1/imunologia , Ligação Proteica , Estrutura Terciária de Proteína , Termodinâmica
7.
Phys Chem Chem Phys ; 23(37): 20919-20935, 2021 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-34541592

RESUMO

Computational studies on the pyrolysis of lignin using electronic structure methods have been largely limited to dimeric or trimeric models. In the current work we have modeled a lignin oligomer consisting of 10 syringyl units linked through 9 ß-O-4' bonds. A lignin model of this size is potentially more representative of the polymer in angiosperms; therefore, we used this representative model to examine the behavior of hardwood lignin during the initial steps of pyrolysis. Using this oligomer, the present work aims to determine if and how the reaction enthalpies of bond cleavage vary with positions within the chain. To accomplish this, we utilized a composite method using molecular mechanics based conformational sampling and quantum mechanically based density functional theory (DFT) calculations. Our key results show marked differences in bond dissociation enthalpies (BDE) with the position. In addition, we calculated standard thermodynamic properties, including enthalpy of formation, heat capacity, entropy, and Gibbs free energy for a wide range of temperatures from 25 K to 1000 K. The prediction of these thermodynamic properties and the reaction enthalpies will benefit further computational studies and cross-validation with pyrolysis experiments. Overall, the results demonstrate the utility of a better understanding of lignin pyrolysis for its effective valorization.


Assuntos
Lignina/química , Celulose/química , Celulose/metabolismo , Teoria da Densidade Funcional , Lignina/metabolismo , Conformação Molecular , Pressão , Pirólise , Temperatura , Termodinâmica
8.
Phys Chem Chem Phys ; 23(34): 18525-18534, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34581329

RESUMO

The ultrafast dynamics triggered by the photodetachment of the tyrosinate dianion in aqueous environment shed light on the elementary processes that accompany the interaction of ionizing radiation with biological matter. Photodetachment of the tryosinate dianion yields the tyrosyl radical anion, an important intermediate in biological redox reactions, although the study of its ultrafast dynamics is limited. Here, we utilize femtosecond optical pump-probe spectroscopy to investigate the ultrafast structural reorganization dynamics that follow the photodetachment of the tyrosinate dianion in aqueous solution. Photodetachment of the tyrosinate dianion leads to vibrational wave packet motion along seven vibrational modes that are coupled to the photodetachment process. The vibrational modes are assigned with the aid of density functional theory (DFT) calculations. Our results offer a glimpse of the elementary dynamics of ionized biomolecules and suggest the possibility of extending this approach to investigate the ionization-induced structural rearrangement of other aromatic amino acids and larger biomolecules.


Assuntos
Radicais Livres/química , Tirosina/química , Ânions/química , Teoria da Densidade Funcional , Hidróxido de Sódio/química , Espectrofotometria , Água/química
9.
Phys Chem Chem Phys ; 23(35): 19911-19922, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34474467

RESUMO

Green fluorescent protein (GFP), together with its family of variants, is the most widely used fluorescent protein for in vivo imaging. Numerous spectroscopic studies of the isolated GFP chromophore have been aimed at understanding the electronic properties of GFP. Here, we build on earlier work [A. V. Bochenkova, C. Mooney, M. A. Parkes, J. Woodhouse, L. Zhang, R. Lewin, J. M. Ward, H. Hailes, L. H. Andersen and H. H. Fielding, Chem. Sci., 2017, 8, 3154] investigating the impact of fluorine and methoxy substituents that have been employed to tune the electronic structure of the GFP chromophore for use as fluorescent RNA tags. We present photoelectron spectra following photoexcitation over a broad range of wavelengths (364-230 nm) together with photoelectron angular distributions following photoexcitation at 364 nm, which are interpreted with the aid of quantum chemistry calculations. The results support the earlier high-level quantum chemistry calculations that predicted how fluorine and methoxy substituents tune the electronic structure and we find evidence to suggest that the methoxy substituents enhance internal conversion, most likely from the 2ππ* state which has predominantly Feshbach resonance character, to the 1ππ* state.


Assuntos
Proteínas de Fluorescência Verde/química , RNA/química , Ânions/química , Teoria da Densidade Funcional , Espectroscopia Fotoeletrônica
10.
Phys Chem Chem Phys ; 23(35): 19130-19140, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34490865

RESUMO

Tetrapyrrole macrocycles serve a multitude of roles in biological systems, including oxygen transport by heme and light harvesting and charge separation by chlorophylls and bacteriochlorophylls. Synthetic tetrapyrroles are utilized in diverse applications ranging from solar-energy conversion to photomedicine. Nevertheless, students beginning tetrapyrrole research, as well as established practitioners, are often puzzled when comparing properties of related tetrapyrroles. Questions arise as to why optical spectra of two tetrapyrroles often shift in wavelength/energy in a direction opposite to that predicted by common chemical intuition based on the size of a π-electron system. Gouterman's four-orbital model provides a framework for understanding these optical properties. Similarly, it can be puzzling as to why the oxidation potentials differ significantly when comparing two related tetrapyrroles, yet the reduction potentials change very little or shift in the opposite direction. In order to understand these redox properties, it must be recognized that structural/electronic alterations affect the four frontier molecular orbitals (HOMO, LUMO, HOMO-1 and LUMO+1) unequally and in many cases the LUMO+1, and not the LUMO, may track the HOMO in energy. This perspective presents a fundamental framework concerning tetrapyrrole electronic properties that should provide a foundation for rational molecular design in tetrapyrrole science.


Assuntos
Tetrapirróis/química , Bacterioclorofilas/química , Clorofila/química , Teoria da Densidade Funcional , Elétrons , Oxirredução , Porfirinas/química , Teoria Quântica
11.
Phys Chem Chem Phys ; 23(35): 19729-19739, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34524307

RESUMO

The fundamental understanding of glucose conversion to 5-ethoxymethylfurfural (EMF) and ethyl levulinate (EL) (value-added chemicals from biomass) in ethanol solution catalyzed by a Brønsted acid is limited at present. Consequently, here, the reaction pathways and mechanism of glucose conversion to EMF and EL catalyzed by a Brønsted acid were studied, using an experimental method and quantum chemical calculations at the B3LYP/6-31G(D) and B2PLYPD3/Def2TZVP level under a polarized continuum model (PCM-SMD). By further verification through GC/MS tests, the mechanism and reaction pathways of glucose conversion in ethanol solution catalyzed by a Brønsted acid were revealed, showing that glucose is catalyzed by proton and ethanol, and ethanol plays a bridging role in the process of proton transfer. There are three main reaction pathways: through glucose and ethyl glucoside (G/EG), through fructose, 5-hydroxymethylfurfural (HMF), levulinic acid (LA), and EL (G/F/H/L/EL), and through fructose, HMF, EMF, and EL (G/F/H/E/EL). The G/F/H/E/EL pathway with an energy barrier of 20.8 kcal mol-1 is considered as the thermodynamic and kinetics primary way, in which the reaction rate of this is highly related to the proton transfer in the isomerization of glucose to fructose. The intermediate HMF was formed from O5 via a ring-opening reaction and by the dehydration of fructose, and was further converted to the main product of EMF by etherification or by LA through hydrolysis. EMF and LA are both unstable, and can partially be transformed to EL. This study is beneficial for the insights aiding the understanding of the process and products controlling biomass conversion in ethanol solution.


Assuntos
Etanol/química , Furaldeído/análogos & derivados , Glucose/química , Modelos Moleculares , Ácidos Sulfúricos/química , Biocombustíveis , Catálise , Teoria da Densidade Funcional , Furaldeído/química , Ácidos Levulínicos/química , Termodinâmica
12.
Phys Chem Chem Phys ; 23(38): 21568-21578, 2021 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-34550129

RESUMO

Prions have been linked to neurodegenerative diseases that affect various species of mammals including humans. The prion protein, located mainly in neurons, is believed to play the role of metal ion transporter. High levels of copper ions have been related to structural changes. A 32-residue region of the N-terminal domain, known as octarepeat, can bind up to four copper ions. Different coordination modes have been observed and are strongly dependent on Cu2+ concentration. Many theoretical studies carried out so far have focused on studying the coordination modes of a single copper ion. In this work we investigate the octarepeat region coordinated with four copper ions. Molecular dynamics (MD) and hybrid quantum mechanics/molecular mechanics (QM/MM) simulations using the polarizable AMOEBA force field have been carried out. The polarizable MD simulations starting from a fully extended conformation indicate that the tetra-Cu2+/octarepeat complex forms a globular structure. The globular form is stabilized by interactions between Cu2+ and tryptophan residues resulting in some coordination sites observed to be in close proximity, in agreement with experimental results. Subsequent QM/MM simulations on several snapshots suggests the system is in a high-spin quintet state, with all Cu2+ bearing one single electron, and all unpaired electrons are ferromagnetically coupled. NMR simulations on selected structures provides insights on the chemical shifts of the first shell ligands around the metals with respect to inter-metal distances.


Assuntos
Complexos de Coordenação/química , Cobre/química , Teoria da Densidade Funcional , Simulação de Dinâmica Molecular , Proteínas Priônicas/química , Elétrons , Conformação Molecular
13.
Phys Chem Chem Phys ; 23(38): 21840-21851, 2021 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-34554171

RESUMO

We assess computationally the adsorption of a series of nitrogen containing heterocycles and fatty acid amides from bio-oil on a model clay surface, Na-montmorillonite. The adsorption energies and conformations predicted by atomistic detail molecular dynamics (MD) simulations are compared against density functional theory (DFT) based molecular electrostatic potentials (MEP) and Hirshfeld, AIM, Merz-Singh-Kollman, and ChelpG charges. MD predicts systematically adsorption via cation bridging with adsorption strength of the heterocycles following purine > pyridine > imidazole > pyrrole > indole > quinoline. The fatty acid amides adsorption strength follows the steric availability and bulkiness of the head group. A comparison against the DFT calculations shows that MEP predicts adsorption geometries and the MD simulations reproduce the conformations for single adsorption site species. However, the DFT derived charge distibutions show that MD force-fields with non-polarizable fixed partial charge representations parametrized for aqueous environments cannot be used in apolar solvent environments without careful accuracy considerations. The overall trends in adsorption energies are reproduced by the Charmm GenFF employed in the MD simulations but the adsorption energies are systematically overestimated in this apolar solvent environment. The work has significance both for revealing nitrogen compound adsorption trends in technologically relevant bio oil environments but also as a methodological assessment revealing the limits of state of the art biomolecular force-fields and simulation protocols in apolar bioenvironments.


Assuntos
Bentonita/química , Compostos de Nitrogênio/química , Óleos Vegetais/química , Polifenóis/química , Adsorção , Teoria da Densidade Funcional , Simulação de Dinâmica Molecular , Tamanho da Partícula , Eletricidade Estática , Propriedades de Superfície
14.
Phys Chem Chem Phys ; 23(38): 21959-21971, 2021 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-34569570

RESUMO

Cisplatin, (NH3)2PtCl2, has been known as a successful metal-based anticancer drug for more than half a century. Its analogue, Argplatin, arginine-linked cisplatin, (Arg)PtCl2, is being investigated because it exhibits reactivity towards DNA and RNA that differs from that of cisplatin. In order to understand the basis for its altered reactivity, the deprotonated and sodium cationized forms of Argplatin, [(Arg-H)PtCl2]- and [(Arg)PtCl2 + Na]+, are examined by infrared multiple photon dissociation (IRMPD) action spectroscopy in the IR fingerprint and hydrogen-stretching regions. Complementary electronic structure calculations are performed using density functional theory approaches to characterize the stable structures of these complexes and to predict their infrared spectra. Comparison of the theoretical IR spectra predicted for various stable conformations of these Argplatin complexes to their measured IRMPD spectra enables determination of the binding mode(s) of Arg to the Pt metal center to be identified. Arginine is found to bind to Pt in a bidentate fashion to the backbone amino nitrogen and carboxylate oxygen atoms in both the [(Arg-H)PtCl2]- and [(Arg)PtCl2 + Na]+ complexes, the NO- binding mode. The neutral side chain of Arg also interacts with the Pt center to achieve additional stabilization in the [(Arg-H)PtCl2]- complex. In contrast, Na+ binds to both chlorido ligands in the [(Arg)PtCl2 + Na]+ complex and the protonated side chain of Arg is stabilized via hydrogen-bonding interactions with the carboxylate moiety. These findings are consistent with condensed-phase results, indicating that the NO- binding mode of arginine to Pt is preserved in the electrospray ionization process even under variable pH and ionic strength.


Assuntos
Antineoplásicos/química , Arginina/química , Cisplatino/química , Óxido Nítrico/química , Platina/química , Sítios de Ligação , Teoria da Densidade Funcional , Estrutura Molecular , Espectrofotometria Infravermelho
15.
Phys Chem Chem Phys ; 23(38): 21951-21958, 2021 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-34569577

RESUMO

In this study, charge updating schemes based on the local polarized protein-specific charge (LPPC) were introduced to vary the atomic charges of the biotin molecule and the residues in close contact during the simulation of the avidin-biotin complexes. The need of the charge variation of the ligand in response to changes in its surroundings was thoroughly studied. The results show that the calculated binding energy difference between biotin (BTN1) and 2'-iminobiotin (BTN2) and avidin is in excellent agreement with the experimental value, thus verifying the feasibility of updating the atomic charges of ligands during the simulation.


Assuntos
Avidina/química , Biotina/química , Sítios de Ligação , Teoria da Densidade Funcional , Conformação Molecular , Simulação de Dinâmica Molecular
16.
Phys Chem Chem Phys ; 23(38): 22119-22132, 2021 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-34580687

RESUMO

The investigation of the structural characteristics of chiral drugs in physiological environments is a challenging research topic, which may lead to a better understanding of how the drugs work. Raman optical activity (ROA) spectroscopy in combination with density functional theory (DFT) calculations was exploited to inspect the structural changes in penicillamine under different acid-base states in aqueous solutions. The B3LYP/aug-cc-PVDZ method was employed and the implicit solvation model density (SMD) was considered for describing the solvation effect in H2O. The conformations of penicillamine varied with pH, but penicillamine was liable to stabilize in the form of the PC conformation (the sulfur atom is in a trans orientation with respect to carboxylate) in most cases for both D- and L-isomers. The relationship between the conformations of penicillamine and the ROA peaks, as well as peak assignments, were comprehensively studied and elucidated. In the fingerprint region, two ROA couplets and one ROA triplet with different patterns were recognized. The intensity, sign and frequency of the corresponding peaks also changed with varying pH. Deuteration was carried out to identify the vibrational modes, and the ROA peaks of the deuterated amino group in particular are sensitive to change in the ambient environment. The results are expected not only to serve as a reference for the interpretation of the ROA spectra of penicillamine and other chiral drugs with analogous structures but also to evaluate the structural changes of chiral molecules in physiological environments, which will form the basis of further exploration of the effects of structural characteristics on the pharmacological and toxicological properties of chiral drugs.


Assuntos
Teoria da Densidade Funcional , Penicilamina/química , Concentração de Íons de Hidrogênio , Conformação Molecular , Análise Espectral Raman , Estereoisomerismo
17.
Phys Chem Chem Phys ; 23(38): 21690-21700, 2021 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-34581354

RESUMO

The biological importance of lanthanides, and the early lanthanides (La3+-Nd3+) in particular, has only recently been recognized, and the structural principles underlying selective binding of lanthanide ions in biology are not yet well established. Lanmodulin (LanM) is a novel protein that displays unprecedented affinity and selectivity for lanthanides over most other metal ions, with an uncommon preference for the early lanthanides. Its utilization of EF-hand motifs to bind lanthanides, rather than the Ca2+ typically recognized by these motifs in other proteins, has led it to be used as a model system to understand selective lanthanide recognition. Two-dimensional infrared (2D IR) spectroscopy combined with molecular dynamics simulations were used to investigate LanM's selectivity mechanisms by characterizing local binding site geometries upon coordination of early and late lanthanides as well as calcium. These studies focused on the protein's uniquely conserved proline residues in the second position of each EF-hand binding loop. We found that these prolines constrain the EF-hands for strong coordination of early lanthanides. Substitution of this proline results in a more flexible binding site to accommodate a larger range of ions but also results in less compact coordination geometries and greater disorder within the binding site. Finally, we identify the conserved glycine in the sixth position of each EF-hand as a mediator of local binding site conformation and global secondary structure. Uncovering fundamental structure-function relationships in LanM informs the development of synthetic biology technologies targeting lanthanides in industrial applications.


Assuntos
Proteínas de Bactérias/química , Complexos de Coordenação/química , Elementos da Série dos Lantanídeos/química , Simulação de Dinâmica Molecular , Teoria da Densidade Funcional , Espectrofotometria Infravermelho
18.
Chem Commun (Camb) ; 57(71): 8985-8988, 2021 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-34486589

RESUMO

A highly concise method for 1,4-diazabicyclo[2.2.2]octane (DABCO) catalyzed [4+2] annulations of o-amino-acylation of aryl MBH carbonates with isocyanates has been developed. For the first time, MBH carbonates served as 1,4-dipoles, providing functionalized 3,4-dihydroquinazolinones in mild conditions with good to excellent yields. The density functional theory calculations of the mechanism supports our hypothesis.


Assuntos
Ésteres/química , Isocianatos/química , Piperazinas/química , Quinazolinonas/síntese química , Catálise , Reação de Cicloadição , Teoria da Densidade Funcional , Modelos Químicos
19.
Molecules ; 26(17)2021 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-34500604

RESUMO

The aqueous synthesis of Pd(II) complexes with alkylated tripeptides led to the hydrolysis of the peptides at low pH values and mixtures of complexed peptides were formed. A non-aqueous synthetic route allowed the formation and isolation of single products and their characterization. Pd(II) complexes with α-Asp(OR)AlaGly(OR), ß-Asp(OR)AlaGly(OR), and TrpAlaGly(OR) (R = H or alkyl) as tri and tetradentate chelates were characterized. The tridentate coordination mode was accompanied by a fourth monodentate ligand that was shown to participate in both ligand exchange reactions and a direct removal to form the tetradentate coordination mode. The tetradentate coordination revealed a rare a hemi labile carbonyl goup coordination mode to Pd(II). Reactivity with small molecules such as ethylene, acids, formate, and episulfide was investigated. Under acidic conditions and in the presence of ethylene; acetaldehyde was formed. The Pd(II) is a soft Lewis acid and thiophilic and the complexes abstract sulfur from episulfide at apparent modest catalytic rates. The complexes adopt a square planar geometry according to a spectroscopic analysis and DFT calculations that were employed to evaluate the most energetically favorable coordination geometry and compared with the observed infrared and NMR data.


Assuntos
Paládio/química , Peptídeos/química , Quelantes/química , Complexos de Coordenação/química , Teoria da Densidade Funcional , Ligantes , Espectroscopia de Ressonância Magnética/métodos
20.
Int J Mol Sci ; 22(18)2021 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-34575970

RESUMO

Using molecular dynamics, we demonstrated that in the mixture of carbon dioxide and ethanol (25% molar fraction) there are three pronounced regions on the p-T diagram characterized by not only high-density fluctuations but also anomalous behavior of thermodynamic parameters. The regions are interpreted as Widom deltas. The regions were identified as a result of analyzing the dependences of density, density fluctuations, isobaric thermal conductivity, and clustering of a mixture of carbon dioxide and ethanol in a wide range of pressures and temperatures. Two of the regions correspond to the Widom delta for pure supercritical carbon dioxide and ethanol, while the third region is in the immediate vicinity of the critical point of the binary mixture. The origin of these Widom deltas is a result of the large mixed linear clusters formation.


Assuntos
Dióxido de Carbono/química , Etanol/química , Simulação de Dinâmica Molecular , Termodinâmica , Teoria da Densidade Funcional , Pressão , Temperatura , Condutividade Térmica
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