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1.
Phys Chem Chem Phys ; 21(37): 21038-21048, 2019 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-31528920

RESUMO

Dramatically different properties have been observed for two types of osmolytes, i.e., trimethylamine N-oxide (TMAO) and urea, in a protein folding process. Great progress has been made in revealing the potential underlying mechanism of these two osmolyte systems. However, many problems still remain unsolved. In this paper, we propose to use the persistent homology to systematically study the osmolytes' molecular aggregation and their hydrogen-bonding network from a global topological perspective. It has been found that, for the first time, TMAO and urea show two extremely different topological behaviors, i.e., an extensive network and local clusters, respectively. In general, TMAO forms highly consistent large loop or circle structures in high concentrations. In contrast, urea is more tightly aggregated locally. Moreover, the resulting hydrogen-bonding networks also demonstrate distinguishable features. With a concentration increase, TMAO hydrogen-bonding networks vary greatly in their total number of loop structures and large-sized loop structures consistently increase. In contrast, urea hydrogen-bonding networks remain relatively stable with slight reduction of the total loop number. Moreover, the persistent entropy (PE) is, for the first time, used in characterization of the topological information of the aggregation and hydrogen-bonding networks. The average PE systematically increases with the concentration for both TMAO and urea, and decreases in their hydrogen-bonding networks. But their PE variances have totally different behaviors. Finally, topological features of the hydrogen-bonding networks are found to be highly consistent with those from the ion aggregation systems, indicating that our topological invariants can characterize intrinsic features of the "structure making" and "structure breaking" systems.


Assuntos
Metilaminas/química , Ureia/química , Entropia , Hidrogênio/química , Ligações de Hidrogênio , Simulação de Dinâmica Molecular , Agregação Patológica de Proteínas , Homologia Estrutural de Proteína
2.
Acta Crystallogr C Struct Chem ; 75(Pt 8): 1031-1035, 2019 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-31380784

RESUMO

Mycobacterium tuberculosis (Mtb), the principal etiological agent of tuberculosis (TB), infects over one-quarter of humanity and is now the leading cause of infectious disease mortality by a single pathogen. Macozinone {2-[4-(cyclohexylmethyl)piperazin-1-yl]-8-nitro-6-(trifluoromethyl)-4H-1,3-benzothiazin-4-one, C20H23F3N4O3S} is a promising new drug for treating drug-sensitive and drug-resistant TB that has successfully completed phase I clinical trials. We report the complete spectroscopic and structural characterization by 1H NMR, 13C NMR, HRMS, IR, and X-ray crystallography. The cyclohexyl moiety is observed to be nearly perpendicular to the core formed by the 1,3-benzothiazin-4-one and piperazine groups. The central piperazine ring adopts a slightly distorted chair conformation caused by sp2-hybridization of the nitro N atom, which donates into the electron-deficient 1,3-benzothiazin-4-one group.


Assuntos
Antituberculosos/química , Antituberculosos/síntese química , Cristalografia por Raios X , Farmacorresistência Bacteriana , Ligações de Hidrogênio , Conformação Molecular , Tuberculose Pulmonar/tratamento farmacológico
3.
Acta Crystallogr C Struct Chem ; 75(Pt 8): 1091-1101, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31380792

RESUMO

A new set of differently hydrated barium and strontium squarates, namely poly[[triaqua(µ-1,2-dioxocyclobut-3-ene-1,2-diolato)barium] monohydrate], {[Ba(C4O4)(H2O)3]·H2O}n (1), poly[[diaqua(µ-1,2-dioxocyclobut-3-ene-1,2-diolato)strontium] monohydrate], {[Sr(C4O4)(H2O)2]·H2O}n (2), and poly[[triaqua(µ-1,2-dioxocyclobut-3-ene-1,2-diolato)barium/strontium(0.85/0.15)] monohydrate], {[Ba0.85Sr0.15(C4O4)(H2O)3]·H2O}n (3), is reported. The study of their crystal structures indicates that all the complexes crystallize in the triclinic space group P-1. Complexes 1 and 3 have a rare combination of squarate units coordinated through monodentate O atoms to two different metal atoms and through two bidentate O atoms to three different metal atoms. Furthermore, they have three coordinated water molecules to give a coordination number of nine. The squarate ligands in complex 2 exhibit two different coordination modes: (i) monodentate O atoms coordinated to four different Sr atoms and (ii) two monodentate O atoms coordinated to two different metal atoms with the other two O atoms bidentate to four different Sr atoms. All the compounds decompose to give the respective carbonates when heated to 800 °C, as evidenced by thermogravimetry/differential thermal analysis (TG-DTA), which are clusters of nanoparticles. Complexes 1 and 3 show additional endothermic peaks at 811 and 820 °C, respectively, indicating the phase transition of BaCO3 from an orthorhombic (α-Pmcn) to a trigonal phase (ß-R3m). All three complexes have significant DNA-binding constants, ranging from 2.45 × 104 to 9.41 × 104 M-1 against EB-CT (ethidium bromide-calf thymus) DNA and protein binding constants ranging from 1.1 × 105 to 8.6 × 105 with bovine serum albumin. The in vitro cytotoxicity of the complexes is indicated by the IC50 values, which range from 128.8 to 261.3 µg ml-1. Complex 3 shows better BSA binding, antioxidant activity against the DPPH radical and cytotoxicity than complexes 1 and 2.


Assuntos
Antineoplásicos/farmacologia , Complexos de Coordenação/farmacologia , Ciclobutanos/farmacologia , Depuradores de Radicais Livres/farmacologia , Substâncias Intercalantes/farmacologia , Animais , Antineoplásicos/síntese química , Antineoplásicos/química , Antineoplásicos/metabolismo , Bário/química , Bovinos , Complexos de Coordenação/síntese química , Complexos de Coordenação/química , Complexos de Coordenação/metabolismo , Cristalografia por Raios X , Ciclobutanos/síntese química , Ciclobutanos/química , Ciclobutanos/metabolismo , DNA/metabolismo , Depuradores de Radicais Livres/síntese química , Depuradores de Radicais Livres/química , Depuradores de Radicais Livres/metabolismo , Humanos , Ligações de Hidrogênio , Substâncias Intercalantes/síntese química , Substâncias Intercalantes/química , Substâncias Intercalantes/metabolismo , Ligantes , Células MCF-7 , Estrutura Molecular , Ligação Proteica , Soroalbumina Bovina/metabolismo , Estrôncio/química , Água/química
4.
Phys Chem Chem Phys ; 21(33): 18105-18118, 2019 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-31396604

RESUMO

With the emergence of drug-resistant Plasmodium falciparum, the treatment of malaria has become a significant challenge; therefore, the development of antimalarial drugs acting on new targets is extremely urgent. In Plasmodium falciparum, type II nicotinamide adenine dinucleotide (NADH) dehydrogenase (NDH-2) is responsible for catalyzing the transfer of two electrons from NADH to flavin adenine dinucleotide (FAD), which in turn transfers the electrons to coenzyme Q (CoQ). As an entry enzyme for oxidative phosphorylation, NDH-2 has become one of the popular targets for the development of new antimalarial drugs. In this study, reliable motion trajectories of the NDH-2 complex with its co-factors (NADH and FAD) and inhibitor, RYL-552, were obtained by comparative molecular dynamics simulations. The influence of cofactor binding on the global motion of NDH-2 was explored through conformational clustering, principal component analysis and free energy landscape. The molecular interactions of NDH-2 before and after its binding with the inhibitor RYL-552 were analyzed, and the key residues and important hydrogen bonds were also determined. The results show that the association of RYL-552 results in the weakening of intramolecular hydrogen bonds and large allosterism of NDH-2. There was a significant positive correlation between the angular change of the key pocket residues in the NADH-FAD-pockets that represents the global functional motion and the change in distance between NADH-C4 and FAD-N5 that represents the electron transfer efficiency. Finally, the possible non-competitive inhibitory mechanism of RYL-552 was proposed. Specifically, the association of inhibitors with NDH-2 significantly affects the global motion mode of NDH-2, leading to widening of the distance between NADH and FAD through cooperative motion induction; this reduces the electron transfer efficiency of the mitochondrial respiratory chain. The simulation results provide useful theoretical guidance for subsequent antimalarial drug design based on the NDH-2 structure and the respiratory chain electron transfer mechanism.


Assuntos
Antimaláricos/química , Cetonas/química , NADH Desidrogenase/antagonistas & inibidores , Plasmodium falciparum/enzimologia , Proteínas de Protozoários/antagonistas & inibidores , Proteínas de Protozoários/química , Quinolinas/química , Transporte de Elétrons , Flavina-Adenina Dinucleotídeo/química , Ligações de Hidrogênio , Modelos Moleculares , Estrutura Molecular , NAD/química , NADH Desidrogenase/química , Oxirredução , Ligação Proteica , Relação Estrutura-Atividade , Termodinâmica
5.
Pharm Res ; 36(10): 150, 2019 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-31428879

RESUMO

PURPOSE: The unconventional tabletability of the indomethacin polymorphs - α and γ - are investigated from a topological and mechanical perspective using powder Brillouin light scattering (p-BLS) to identify the specific structure-performance relationship in these materials. METHOD: Indomethacin (γ-form) was purchased and used to prepare the α polymorph. Powder X-ray diffraction was used to confirm phase identity, while p-BLS was used to obtain the mechanical properties. Energy frameworks were determined with Crystal Explorer to visualize the interaction topologies. Using a Carver press and a stress-strain analyzer, the tableting performance of each polymorph was determined. RESULTS: Polymorph-specific acoustic frequency distributions were observed with distinct, zero-porosity, aggregate elastic moduli determined. The p-BLS spectra for α-indomethacin display a population of low-velocity shear modes, indicating a direction of facilitated shear. This improves slip-mediated plasticity and tabletability. Our p-BLS spectra experimentally indicates that a low-energy slip system is available to α-indomethacin which supports ours and previous energy framework calculations. Despite a 2d-layered crystal motif favorable for shear deformation, the γ-form displays a higher shear modulus that is supported by our hydrogen-bonding analysis of γ-indomethacin. CONCLUSION: Our experimental, mechanical data is consistent with the predicted interaction topologies and these two inputs combined permit a comprehensive, molecular understanding of polymorph-specific tabletability.


Assuntos
Indometacina/química , Cristalização , Dimerização , Composição de Medicamentos , Ligações de Hidrogênio , Luz , Fenômenos Mecânicos , Porosidade , Pós , Espalhamento de Radiação , Comprimidos , Termodinâmica
6.
Phys Chem Chem Phys ; 21(32): 17893-17900, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31380529

RESUMO

The dispersion interaction was reported to play a critical role in the stabilization of model dipeptide Z-Arg-OH, even greater than the conventional hydrogen bond (HB), which is opposite to the traditional opinion. Here the conformation of Z-Arg-OH has been systematically searched by the effective fragment based step-by-step strategy. All the newly-found low-energy conformers determined at the advanced DSD-PBEP86-D3(BJ)/aug-cc-pVTZ level are clearly in the stretched form with strong conventional HBs, rather than the reported folded structures with emphasis on the dispersion interactions. The simulated IR spectra of the stretched conformers fit better than those of the folded ones compared with the previous experimental observations. Near-edge X-ray absorption fine-structure (NEXAFS) spectra and X-ray photoelectron spectra (XPS) at C, N and O K-edges have also been simulated to unambiguously identify different isomers. This work thus provides valuable insight into the competitions between the conventional HB and the dispersion interactions and demonstrates that the conventional hydrogen bonding is still more important for such small peptides.


Assuntos
Arginina/análogos & derivados , Arginina/química , Dipeptídeos/química , Modelos Moleculares , Ligações de Hidrogênio , Isomerismo , Fenômenos Físicos , Conformação Proteica , Estabilidade Proteica , Solventes/química , Termodinâmica
7.
J Phys Chem A ; 123(32): 7087-7103, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31323178

RESUMO

The Cremer-Pople ring puckering analysis and the Konkoli-Cremer local mode analysis supported by the topological analysis of the electron density were applied for the first comprehensive analysis of the interplay between deoxyribose ring puckering and intramolecular H-bonding in 2'-deoxycytidine, 2'-deoxyadenosine, 2'-deoxythymidine, and 2'-deoxyguanosine. We mapped for each deoxyribonucleoside the complete conformational energy surface and the corresponding pseudorotation path. We found only incomplete pseudorotation cycles, caused by ring inversion, which we coined as pseudolibration paths. On each pseudolibration path a global and a local minimum separated by a transition state were identified. The investigation of H-bond free deoxyribonucleoside analogs revealed that removal of the H-bond does not restore the full conformational flexibility of the sugar ring. Our work showed that ring puckering predominantly determines the conformational energy; the larger the puckering amplitude, the lower the conformational energy. In contrast no direct correlation between conformational energy and H-bond strength was found. The longest and weakest H-bonds are located in the local minimum region, whereas the shortest and strongest H-bonds are located outside the global and local minimum regions at the turning points of the pseudolibration paths, i.e., H-bonding determines the shape and length of the pseudolibration paths. In addition to the H-bond strength, we evaluated the covalent/electrostatic character of the H-bonds applying the Cremer-Kraka criterion of covalent bonding. H-bonding in the puric bases has a more covalent character whereas in the pyrimidic bases the H-bond character is more electrostatic. We investigated how the mutual orientation of the CH2OH group and the base influences H-bond formation via two geometrical parameters describing the rotation of the substituents perpendicular to the sugar ring and their tilting relative to the ring center. According to our results, rotation is more important for H-bond formation. In addition we assessed the influence of the H-bond acceptor, the lone pair (N, respectively O), via the delocalization energy. We found larger delocalization energies corresponding to stronger H-bonds for the puric bases. The global minimum conformation of 2'-deoxyguanosine has the strongest H-bond of all conformers investigated in this work with a bond strength of 0.436 which is even stronger than the H-bond in the water dimer (0.360). The application of our new analysis to DNA deoxyribonucleotides and to unnatural base pairs, which have recently drawn a lot of attention, is in progress.


Assuntos
Desoxirribonucleosídeos/química , DNA/química , Ligações de Hidrogênio , Conformação de Ácido Nucleico , Termodinâmica
8.
Molecules ; 24(13)2019 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-31288375

RESUMO

Ureido-N-iso-propyl,N'-4-(3-pyridin-2-one)pyrimidine (1) and its 2-methoxy pyridine derivative (1Me) has been designed and prepared. The conformational equilibrium in urea moiety and tautomerism in the pyrimidine part have been investigated by variable temperature and 1H NMR titrations as well as DFT quantum chemical calculations. The studied compounds readily associate by triple hydrogen bonding with 2-aminonaphthyridine (A) and/or 2,6-bis(acetylamino)pyridine (B). In 1, the proton is forced to 1,3-tautomeric shift upon stimuli and keeps it position, even when one of the partners in the complex was replaced by another molecule. The observed tautomerism controlled by conformational state (kinetic trapping effect) opens new possibilities in molecular sensing that are based on the fact that reverse reaction is not preferred.


Assuntos
Pirimidinas/síntese química , Ureia/análogos & derivados , Ureia/síntese química , Catálise , Ligações de Hidrogênio , Isomerismo , Cinética , Conformação Molecular , Prótons , Teoria Quântica , Temperatura Ambiente , Termodinâmica
9.
Nat Commun ; 10(1): 2915, 2019 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-31266946

RESUMO

The bile acid-sensing transcription factor farnesoid X receptor (FXR) regulates multiple metabolic processes. Modulation of FXR is desired to overcome several metabolic pathologies but pharmacological administration of full FXR agonists has been plagued by mechanism-based side effects. We have developed a modulator that partially activates FXR in vitro and in mice. Here we report the elucidation of the molecular mechanism that drives partial FXR activation by crystallography- and NMR-based structural biology. Natural and synthetic FXR agonists stabilize formation of an extended helix α11 and the α11-α12 loop upon binding. This strengthens a network of hydrogen bonds, repositions helix α12 and enables co-activator recruitment. Partial agonism in contrast is conferred by a kink in helix α11 that destabilizes the α11-α12 loop, a critical determinant for helix α12 orientation. Thereby, the synthetic partial agonist induces conformational states, capable of recruiting both co-repressors and co-activators leading to an equilibrium of co-activator and co-repressor binding.


Assuntos
Receptores Citoplasmáticos e Nucleares/agonistas , Receptores Citoplasmáticos e Nucleares/química , Animais , Linhagem Celular , Proteínas Correpressoras/genética , Proteínas Correpressoras/metabolismo , Humanos , Ligações de Hidrogênio , Ligantes , Fígado/metabolismo , Espectroscopia de Ressonância Magnética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Ligação Proteica , Conformação Proteica em alfa-Hélice , Receptores Citoplasmáticos e Nucleares/genética , Receptores Citoplasmáticos e Nucleares/metabolismo
10.
Science ; 365(6449): 124-125, 2019 07 12.
Artigo em Inglês | MEDLINE | ID: mdl-31296757
11.
Chem Commun (Camb) ; 55(66): 9761-9764, 2019 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-31355386

RESUMO

The effect of ions on the structure and dynamics of a spider silk protein is elucidated. Chaotropic ions prevent intra- and inter-molecular interactions on the repetitive domain, which are required to maintain the solubility, while kosmotropic ions promote hydrogen bond interactions in the glycine-rich region, which are a prerequisite for ß-sheet formation.


Assuntos
Conformação Proteica em Folha beta , Seda/química , Animais , Cloretos/química , Ligações de Hidrogênio , Concentração de Íons de Hidrogênio , Ressonância Magnética Nuclear Biomolecular/métodos , Proteínas Recombinantes/química , Sódio/química , Solubilidade , Aranhas
12.
Chem Commun (Camb) ; 55(66): 9797-9800, 2019 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-31360962

RESUMO

Molecular tubes with hydrogen bonding donors in their deep hydrophobic cavities are able to selectively bind organophosphorus compounds in water through hydrogen bonding and the hydrophobic effect. They can also be used as a fluorescent sensor for nerve agent simulants and as an inhibitor to reduce the toxicity of paraoxon to acetylcholinesterase.


Assuntos
Acetilcolinesterase/efeitos dos fármacos , Inibidores da Colinesterase/química , Inibidores da Colinesterase/toxicidade , Agentes Neurotóxicos/química , Agentes Neurotóxicos/toxicidade , Paraoxon/química , Paraoxon/toxicidade , Calorimetria , Corantes Fluorescentes/química , Ligações de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Espectroscopia de Ressonância Magnética/métodos , Termodinâmica , Água/química
13.
Phys Chem Chem Phys ; 21(29): 15988-16004, 2019 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-31297500

RESUMO

S-Sulfhydration of cysteine to the Cys-SSH persulfide is an oxidative post-translational modification that plays an important regulatory role in many physiological systems. Though hydrogen persulfide (H2S2) has recently been established as a signaling and cellular sulfhydration reagent, the chemistry and chemical biology of persulfides remain poorly explored. We first report an extensive high-level ab initio quantum chemical investigation of (H2S2)n, (H2S2)m·H2O, and (H2O)m·H2S2 clusters (n = 1-3 and m = 1, 2) and of H2S2 complexes with 19 compounds that model the side chains of naturally-occurring amino acids. The high polarizability of S necessitates the use of large, very diffuse, basis sets for proper description of H2S2 and its complexes. H2S2 possesses a skewed equilibrium geometry, with nonpolar trans and more polar cis conformers 6 and 8 kcal mol-1 higher in energy, respectively; the skewed conformation is preserved in all neutral and cationic complexes while a cis geometry prevails in some anionic complexes. H2S2 is found to be a better H-bond donor and a poorer acceptor than H2S, and that in complexes with H2O, alcohols and amines, H2S2 is a better H-bond donor. Radical delocalization on both S atoms stabilizes the perthiyl (HSS˙) over the thiyl (HS˙) radical and results in a ∼20 kcal mol-1 lower S-H homolytic bond dissociation in H2S2, making it a potential antioxidant. A simple additive model is optimized for H2S2 and used together with the TIP3P model and the CHARMM36 all-atom force field (FF) to investigate the structure and thermodynamic properties of liquid H2S2 and the solubility of H2S2 in water, and to model H2S2-protein interactions (for which new FF parameters are further developed). Very weak H-bonding characterizes liquid H2S2 and it is found immiscible in liquid water with a trend in H-bonding strengths between H2S2 and H2O in the order O-HO ≫ S-HO > O-HS. This work does not only provide a thorough description of the structure and energetics of H2S2 and its various complexes, but also yields a reliable FF for investigating H2S2 in chemistry and biology.


Assuntos
Simulação por Computador , Modelos Químicos , Sulfetos/química , Hidrogênio/química , Ligações de Hidrogênio , Termodinâmica
14.
Food Chem ; 299: 125108, 2019 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-31310914

RESUMO

Macroporous resins have been employed in the effective recovery of flavonoids from plants. In this study, S8 polar resins were used to recover flavonoids and procyanidins from lotus seedpods. Adsorption kinetics, isotherms, and thermodynamics studies revealed that the adsorption process involved physico-chemical interactions, including flavonoid-resin and flavonoid-flavonoid electrostatic interactions, π-π aromatic stacking, moderate and strong hydrogen bonding, and repulsive forces. These forces worked complementarily in adsorption, except for the repulsive force, which opposed the adsorption. Further, adsorption temperature determined the adsorption behavior, with multilayer adsorption enhancing adsorption capacity. In dynamic desorption tests, an acetone/water/acetic acid mixture (58.77: 39.34: 1.89) designed by the D-optimal design method was able to desorb 95.57% and 89.85% of total flavonoids and procyanidins, respectively, using less than two bed volumes of solvent. Ultra-performance liquid chromatography triple-time of flight/mass spectrometry (UPLC-TOF/MS) analysis showed that 26 flavonoids, including 5 procyanidins, were detected after the recovery.


Assuntos
Flavonoides/isolamento & purificação , Nelumbo/química , Resinas Sintéticas/química , Sementes/química , Adsorção , Cromatografia Líquida de Alta Pressão/métodos , Flavonoides/análise , Flavonoides/química , Ligações de Hidrogênio , Espectrometria de Massas , Proantocianidinas/análise , Proantocianidinas/química , Proantocianidinas/isolamento & purificação , Eletricidade Estática
15.
Phys Chem Chem Phys ; 21(28): 15463-15470, 2019 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-31257373

RESUMO

Effective treatment of disorders of the central nervous system can often be achieved using bioactive molecules of similar moieties to those known to be tolerable. A better understanding of the solid-state characteristics of such molecules could thereby create new opportunities for research on pharmaceutical preparations and drug prescriptions, while information about their rich intramolecular dynamics may well add an important aspect in the field of in silico drug discovery. We have therefore investigated three different antipsychotic drugs: haloperidol (C21H23ClFNO2, HAL), aripiprazole (C23H27Cl2N3O2, APZ) and quetiapine hemifumarate (C21H25N3O2S·0.5C4H4O4, QTP) based on similarities either in their structures, hydrophobic and hydrophilic moieties, or in their modes of action, typical or atypical. Our aim was to test the structural and molecular stability of these three different antipsychotics. To this end, we compared the molecular vibrations observed by inelastic neutron spectroscopy of these systems with those from theoretical periodic calculations of the crystalline antipsychotics using the Vienna ab initio simulation package (VASP). While most of the observed features in the lattice region were reasonably well represented by the calculations, the overall spectra were relatively complex, and hence traditional assignment procedures for the approximately 600 normal modes in the unit cell were not possible. These results indicate that in the search for new drug candidates, not only analysis of the flexibility of the receptor, but also the dynamics of the active molecules play a role in improving the prediction of binding affinities.


Assuntos
Antipsicóticos/química , Conformação Molecular , Ligações de Hidrogênio
16.
J Phys Chem A ; 123(28): 5995-6002, 2019 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-31268326

RESUMO

High-resolution X-ray crystallography and two-dimensional NMR studies demonstrate that water-mediated conventional hydrogen-bonding interactions (N-H···N, O-H···N, etc.) bridging two or more amino acid residues contribute to the stability of proteins and protein-ligand complexes. In this work, we have investigated single water-mediated selenium hydrogen-bonding interactions (unconventional hydrogen-bonding) between amino acid residues in proteins through extensive protein data bank (PDB) analysis coupled with gas-phase spectroscopy and quantum chemical calculation of a model complex consisting of indole, dimethyl selenide, and water. Here, indole and dimethyl selenide represent the amino acid residues tryptophan and selenomethionine, respectively. The current investigation demonstrates that the most stable structure of the model complex observed in the IR spectroscopy mimics single water-mediated selenium hydrogen-bonded structural motifs present in the crystal structures of proteins. The present work establishes that water-mediated Se hydrogen-bonding interactions are ubiquitous in proteins and the number of these interactions observed in the PDB is more than that of direct Se hydrogen-bonds present there.


Assuntos
Proteínas/química , Selênio/química , Água/química , Biologia Computacional , Cristalografia por Raios X , Bases de Dados de Proteínas , Ligações de Hidrogênio , Indóis/química , Ligantes , Modelos Moleculares , Compostos Organosselênicos/química , Teoria Quântica , Selenometionina/química , Espectrofotometria Infravermelho , Triptofano/química
17.
Chem Commun (Camb) ; 55(65): 9697-9700, 2019 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-31347623

RESUMO

An ultra-high sensitivity sensor with the function of chiral signal amplification has been proposed for the enantiomer discrimination of various amino acid enantiomers based on charge transfer (CT)-induced SERS spectroscopy. The introduced TiO2 in this sensor improves the CT behavior and discrimination efficiency distinctly and enantiomeric discrimination is realized even at low concentration.


Assuntos
Compostos de Anilina/química , Nanopartículas Metálicas/química , Compostos de Sulfidrila/química , Triptofano/análise , beta-Ciclodextrinas/química , Ligações de Hidrogênio , Fenilalanina/análise , Fenilalanina/química , Prata/química , Análise Espectral Raman/métodos , Estereoisomerismo , Titânio/química , Triptofano/química , Tirosina/análise , Tirosina/química
18.
Phys Chem Chem Phys ; 21(31): 17142-17151, 2019 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-31339149

RESUMO

In this work we compute high-coverage hydrogen adsorption energies and geometries on the stepped platinum surfaces Pt(211) and Pt(533) which contain a (100)-step type and the Pt(221) and Pt(553) surface with a (111) step edge. We discuss these results in relation to ultra-high-vacuum temperature programmed desorption (TPD) data to elucidate the origin of the desorption features. Our results indicated that on surfaces with a (100)-step type, two distinct ranges of adsorption energy for the step and terrace are observed, which mirrors the TPD spectra for which we find a clear separation of the desorption peaks. For the (111) step type, the TPD spectra show much less separation of the step and terrace features, which we assign to the low individual adsorption energies for H atoms on this step edge. From our results we obtain a much clearer understanding of the surface-hydrogen bonding at high coverages and the origin of the different TPD features present for the two step types studied.


Assuntos
Teoria da Densidade Funcional , Hidrogênio/química , Platina/química , Adsorção , Cristalização , Ligações de Hidrogênio , Temperatura Ambiente , Termodinâmica
19.
J Phys Chem Lett ; 10(15): 4278-4284, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31318218

RESUMO

Silk continues to amaze: over the past decade, new research threads have emerged that include the use of silk fibroin for advanced pharmaceutics, including its suitability for drug delivery. Despite this ongoing interest, the details of silk fibroin structures and their subsequent drug interactions at the molecular level remain elusive, primarily because of the difficulties encountered in modeling the silk fibroin molecule. Here, we generated an atomistic silk model containing amorphous and crystalline regions. We then exploited advanced well-tempered metadynamics simulations to generate molecular conformations that we subsequently exposed to classical molecular dynamics simulations to monitor both drug binding and release. Overall, this study demonstrated the importance of the silk fibroin primary sequence, electrostatic interactions, hydrogen bonding, and higher-order conformation in the processes of drug binding and release.


Assuntos
Doxorrubicina/química , Portadores de Fármacos/química , Fibroínas/química , Animais , Bombyx/química , Cristalização , Liberação Controlada de Fármacos , Ligações de Hidrogênio , Simulação de Dinâmica Molecular , Conformação Proteica , Eletricidade Estática , Termodinâmica , Água/química
20.
Plant Foods Hum Nutr ; 74(3): 328-333, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31172349

RESUMO

Rutin possesses a wide range of application prospects with various bioactivities. However, its bitter and water-insoluble properties restrict its application in the field of functional foods. A new complex of rutin and chitooligosaccharide (Rutin-COS) was prepared via spray-drying method (100 °C, 1 L/h) and freeze-drying method (-80 °C, 24 h), respectively. The water solubility, bitterness, antioxidant and antibacterial activities of Rutin-COS were evaluated, and the complexation of Rutin-COS was characterized by SEM, 1H-NMR and ROESY. Compared to freeze-drying method, spray-drying method was more effective for preparing stable Rutin-COS complex. The spray-dried Rutin-COS showed increased water solubility, weakened bitterness, enhanced antioxidant and antibacterial activity compared to rutin. The Rutin-COS complex was demonstrated to be formed through hydrogen bonds between the A, B rings of rutin and COS.


Assuntos
Antibacterianos/farmacologia , Antioxidantes/farmacologia , Quitina/análogos & derivados , Dessecação/métodos , Rutina/química , Quitina/química , Quitina/farmacologia , Liofilização/métodos , Ligações de Hidrogênio , Rutina/farmacologia , Solubilidade , Paladar , Água/química
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