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1.
Mar Drugs ; 17(12)2019 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-31795126

RESUMO

KTM is a 16 amino acid peptide with the sequence WCCSYPGCYWSSSKWC. Here, we present the nuclear magnetic resonance (NMR) structure and bioactivity of this rationally designed α-conotoxin (α-CTx) that demonstrates potent inhibition of rat α3ß2-nicotinic acetylcholine receptors (rα3ß2-nAChRs). Two bioassays were used to test the efficacy of KTM. First, a qualitative PC12 cell-based assay confirmed that KTM acts as a nAChR antagonist. Second, bioactivity evaluation by two-electrode voltage clamp electrophysiology was used to measure the inhibition of rα3ß2-nAChRs by KTM (IC50 = 0.19 ± 0.02 nM), and inhibition of the same nAChR isoform by α-CTx MII (IC50 = 0.35 ± 0.8 nM). The three-dimensional structure of KTM was determined by NMR spectroscopy, and the final set of 20 structures derived from 32 distance restraints, four dihedral angle constraints, and two disulfide bond constraints overlapped with a mean global backbone root-mean-square deviation (RMSD) of 1.7 ± 0.5 Å. The structure of KTM did not adopt the disulfide fold of α-CTx MII for which it was designed, but instead adopted a flexible ribbon backbone and disulfide connectivity of C2-C16 and C3-C8 with an estimated 12.5% α-helical content. In contrast, α-CTx MII, which has a native fold of C2-C8 and C3-C16, has an estimated 38.1% α-helical secondary structure. KTM is the first reported instance of a Framework I (CC-C-C) α-CTx with ribbon connectivity to display sub-nanomolar inhibitory potency of rα3ß2-nAChR subtypes.

2.
J Phys Chem A ; 123(32): 6937-6947, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31099570

RESUMO

Solid-state density functional theory (DFT), molecular dynamics (MD), and terahertz (THz) spectroscopy were used to study the formation of enantiotropically related conformational Form I and Form II polymorphs of the pharmaceutical compound, probucol. DFT calculations were performed on the crystal systems to compare relative lattice energies and the solvent stabilization of the metastable Form II structure. The thermodynamics of solvent inclusion in the Form II·MeOH crystal system were determined from MD simulations, as was the favored conformation of molecular probucol in methanol and ethanol solutions. The findings from both solid-state DFT and MD calculations suggest that the preferred molecular orientations of the probucol molecule in solution and the probable inclusion of methanol in the crystal lattice during the crystallization process lead to the solvent selectivity of the probucol polymorph formation. The additional stabilization energy provided by the crystallization solvent facilitates the nucleation and growth of the Form II polymorph under conditions that favor this metastable crystal form over the thermodynamically stable Form I, despite the higher energy molecular and crystalline configurations of probucol Form II. We demonstrate the influence of solvent on the formation of pharmaceutical polymorphs and provide a molecular-level view of complex interactions leading to polymorphism using a combination of computational methods and THz spectral data.


Assuntos
Teoria da Densidade Funcional , Simulação de Dinâmica Molecular , Preparações Farmacêuticas/química , Cristalização , Solventes/química , Espectroscopia Terahertz , Termodinâmica
3.
Inorg Chem ; 58(12): 8130-8139, 2019 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-31124666

RESUMO

An investigation of supramolecular phenomena involving zerovalent transition metal complexes was facilitated by the production of the ditopic isocyanide ligand 1,3-bis( p-isocyanophenyl)urea, which was synthesized via substoichiometric phosgenation of 4-isocyanophenylamine and used to coordinate group VI metal carbonyl fragments. The resulting binuclear organometallic complexes were observed to pack into ladder-like anisotropic arrays in the solid state. Crystallographic and computational evidence suggests that this packing motif can be attributed to a combination of intermolecular π-π and urea-π interactions. Similar to other N, N'-diarylureas bearing electron-withdrawing groups, 1,3-bis( p-isocyanophenyl)urea and the organometallic complexes prepared therefrom also exhibit an affinity toward anion binding in nonaqueous solution. Equilibrium constants ( K) for the formation of host-guest complexes between the organometallic derivatives of 1,3-bis( p-isocyanophenyl)urea and chloride, nitrate, and acetate anions exceed 103, 104, and 105 M-1, respectively.

4.
BMC Bioinformatics ; 19(1): 138, 2018 04 16.
Artigo em Inglês | MEDLINE | ID: mdl-29661129

RESUMO

BACKGROUND: Conventional de novo drug design is costly and time consuming, making it accessible to only the best resourced research organizations. An emergent approach to new drug development is drug repurposing, in which compounds that have already gone through some level of clinical testing are examined for efficacy against diseases divergent than their original application. Repurposing of existing drugs circumvents the time and considerable cost of early stages of drug development, and can be accelerated by using software to screen existing chemical databases to identify suitable drug candidates. RESULTS: Small-molecule Peptide-Influenced Drug Repurposing (SPIDR) was developed to identify small molecule drugs that target a specific receptor by exploring the conformational binding space of peptide ligands. SPIDR was tested using the potent and selective 16-amino acid peptide α-conotoxin MII ligand and the α3ß2-nicotinic acetylcholine receptor (nAChR) isoform. SPIDR incorporates a genetic algorithm-based, heuristic search procedure, which was used to explore the ligand binding domain of the α3ß2-nAChR isoform using a library consisting of 640,000 α-conotoxin MII peptide analogs. The peptides that exhibited the highest affinity for α3ß2-nAChR were used as models for a small-molecule structure similarity search of the PubChem Compound database. SPIDR incorporates the SimSearcher utility, which generates shape distribution signatures of molecules and employs multi-level K-means clustering to insure fast database queries. SPIDR identified non-peptide drugs with estimated binding affinities nearly double that of the native α-conotoxin MII peptide. CONCLUSIONS: SPIDR has been generalized and integrated into DockoMatic v 2.1. This software contains an intuitive graphical interface for peptide mutant screening workflow and facilitates mapping, clustering, and searching of local molecular databases, making DockoMatic a valuable tool for researchers in drug design and repurposing.


Assuntos
Reposicionamento de Medicamentos , Peptídeos/farmacologia , Bibliotecas de Moléculas Pequenas/farmacologia , Software , Sequência de Aminoácidos , Conotoxinas/química , Conotoxinas/metabolismo , Ligantes , Modelos Moleculares , Conformação Molecular , Peptídeos/química , Receptores Nicotínicos/química , Receptores Nicotínicos/metabolismo
5.
Nat Commun ; 8(1): 18, 2017 05 26.
Artigo em Inglês | MEDLINE | ID: mdl-28550308

RESUMO

The endoplasmic reticulum, the cytoplasmic organelle that matures a massive amount of nascent secretory polypeptides, is particularly sensitive to stress. Endoplasmic reticulum stress causes unfolded proteins to populate the organelle, eliciting the unfolded protein response. During the unfolded protein response, GRP78-an endoplasmic reticulum master stress regulator-detaches from three endoplasmic reticulum stress sensors (IRE1α, PERK, and ATF6) and allows them to activate the apoptotic signaling pathway. Fortilin, a pro-survival molecule, is known to inhibit apoptosis by binding and inhibiting p53, but its role in endoplasmic reticulum stress-induced apoptosis remains unknown. Here, we report that fortilin directly interacts with the cytoplasmic domain of IRE1α, inhibits both kinase and endoribonuclease (RNase) activities of the stress sensor, and protects cells against apoptotic cell death at both cellular and whole animal levels. Our data support a role of fortilin in the unfolded protein response and its potential participation in human diseases caused by unfolded protein response.IRE1α is an ER stress sensor, whose activity induces apoptosis. Here, the authors report that fortilin, a pro-survival factor, with yet unknown roles in ER stress, interacts with active IRE1α, inhibits both its kinase end RNase activities, and protects cells from apoptosis both in vitro and in vivo.


Assuntos
Biomarcadores Tumorais/genética , Estresse do Retículo Endoplasmático/genética , Endorribonucleases/genética , Proteínas de Choque Térmico/genética , Proteínas Serina-Treonina Quinases/genética , Resposta a Proteínas não Dobradas , Fator 6 Ativador da Transcrição/genética , Fator 6 Ativador da Transcrição/metabolismo , Animais , Apoptose , Biomarcadores Tumorais/metabolismo , Linhagem Celular Tumoral , Retículo Endoplasmático/genética , Retículo Endoplasmático/metabolismo , Endorribonucleases/metabolismo , Células Epiteliais/citologia , Células Epiteliais/metabolismo , Regulação da Expressão Gênica , Proteínas de Choque Térmico/metabolismo , Humanos , Camundongos , Osteoblastos/citologia , Osteoblastos/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Transdução de Sinais , Transdução Genética , eIF-2 Quinase/genética , eIF-2 Quinase/metabolismo
6.
J Chem Inf Model ; 56(12): 2378-2387, 2016 12 27.
Artigo em Inglês | MEDLINE | ID: mdl-28024403

RESUMO

This study demonstrates the utility of genetic algorithms to search exceptionally large and otherwise intractable mutant libraries for sequences with optimal binding affinities for target receptors. The Genetic Algorithm Managed Peptide Mutant Screening (GAMPMS) program was used to search an α-conotoxin (α-CTx) MII mutant library of approximately 41 billion possible peptide sequences for those exhibiting the greatest binding affinity for the α3ß2-nicotinic acetylcholine receptor (nAChR) isoform. A series of top resulting peptide ligands with high sequence homology was obtained, with each mutant having an estimated ΔGbind approximately double that of the potent native α-CTx MII ligand. A consensus sequence from the top GAMPMS results was subjected to more rigorous binding free energy calculations by molecular dynamics and compared to α-CTx MII and other related variants for binding with α3ß2-nAChR. In this study, the efficiency of GAMPMS to substantially reduce the sample population size through evolutionary selection criteria to produce ligands with higher predicted binding affinity is demonstrated.


Assuntos
Conotoxinas/farmacologia , Antagonistas Nicotínicos/farmacologia , Biblioteca de Peptídeos , Receptores Nicotínicos/metabolismo , Algoritmos , Sequência de Aminoácidos , Animais , Conotoxinas/química , Conotoxinas/genética , Descoberta de Drogas , Humanos , Modelos Moleculares , Mutação , Antagonistas Nicotínicos/química , Antagonistas Nicotínicos/metabolismo , Ligação Proteica , Ratos , Software
7.
Bioorg Med Chem ; 24(16): 3752-7, 2016 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-27338657

RESUMO

Veratrum californicum, commonly referred to as corn lily or Californian false hellebore, grows in high mountain meadows and produces the steroidal alkaloid cyclopamine, a potent inhibitor of the Hedgehog (Hh) signaling pathway. The Hh pathway is a crucial regulator of many fundamental processes during vertebrate embryonic development. However, constitutive activation of the Hh pathway contributes to the progression of various cancers. In the present study, a direct correlation was made between the extraction efficiency for cyclopamine from root and rhizome by eight methods, and the associated biological activity in Shh-Light II cells using the Dual-Glo® Luciferase Assay System. Alkaloid recovery ranged from 0.39 to 8.03mg/g, with ethanol soak being determined to be the superior method for obtaining biologically active cyclopamine. Acidic ethanol and supercritical extractions yielded degraded or contaminated cyclopamine with lower antagonistic activity towards Hh signaling.


Assuntos
Alcaloides de Veratrum/farmacologia , Veratrum/química , Biomassa , Linhagem Celular , Cromatografia Líquida de Alta Pressão , Proteínas Hedgehog/antagonistas & inibidores , Proteínas Hedgehog/metabolismo , Transdução de Sinais/efeitos dos fármacos , Alcaloides de Veratrum/isolamento & purificação
8.
Nat Prod Commun ; 11(5): 607-9, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-27319129

RESUMO

Current United States regulatory policies allow for the addition of pharmacologically active substances in dietary supplements if derived from a botanical source. The inclusion of certain nootropic drugs, such as vinpocetine, in dietary supplements has recently come under scrutiny due to the lack of defined dosage parameters and yet unproven short- and long-term benefits and risks to human health. This study quantified the concentration of vinpocetine in several commercially available dietary supplements and found that a highly variable range of 0.6-5.1 mg/serving was present across the tested products, with most products providing no specification of vinpocetine concentrations.


Assuntos
Suplementos Nutricionais/análise , Nootrópicos/análise , Alcaloides de Vinca/análise
9.
Biochem Mol Biol Educ ; 44(1): 63-7, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26537635

RESUMO

Computational molecular docking is a fast and effective in silico method for the analysis of binding between a protein receptor model and a ligand. The visualization and manipulation of protein to ligand binding in three-dimensional space represents a powerful tool in the biochemistry curriculum to enhance student learning. The DockoMatic tutorial described herein provides a framework by which instructors can guide students through a drug screening exercise. Using receptor models derived from readily available protein crystal structures, docking programs have the ability to predict ligand binding properties, such as preferential binding orientations and binding affinities. The use of computational studies can significantly enhance complimentary wet chemical experimentation by providing insight into the important molecular interactions within the system of interest, as well as guide the design of new candidate ligands based on observed binding motifs and energetics. In this laboratory tutorial, the graphical user interface, DockoMatic, facilitates docking job submissions to the docking engine, AutoDock 4.2. The purpose of this exercise is to successfully dock a 17-amino acid peptide, α-conotoxin TxIA, to the acetylcholine binding protein from Aplysia californica-AChBP to determine the most stable binding configuration. Each student will then propose two specific amino acid substitutions of α-conotoxin TxIA to enhance peptide binding affinity, create the mutant in DockoMatic, and perform docking calculations to compare their results with the class. Students will also compare intermolecular forces, binding energy, and geometric orientation of their prepared analog to their initial α-conotoxin TxIA docking results.


Assuntos
Bioquímica/educação , Biologia Computacional , Peptídeos/metabolismo , Receptores de Superfície Celular/metabolismo , Estudantes , Sítios de Ligação , Simulação de Acoplamento Molecular
10.
Opt Express ; 21(7): 8269-75, 2013 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-23571917

RESUMO

Vibrational spectroscopy has been widely applied in different fields due to its label-free chemical-sensing capability. Coherent anti-Stokes Raman scattering (CARS) provides stronger signal and faster acquisition than spontaneous Raman scattering, making it especially suitable for molecular imaging. Coherently-controlled single-beam CARS simplifies the conventional multi-beam setup, but the vibrational bandwidth and non-trivial spectrum retrieval have been limiting factors. In this work, a coherent supercontinuum generated in an all-normal-dispersion nonlinear fiber is phase-shaped within a narrow bandwidth for broadband vibrational spectroscopy. The Raman spectra can be directly retrieved from the CARS measurements, covering the fingerprint regime up to 1750 cm(-1). The retrieved spectra of several chemical species agree with their spontaneous Raman data. The compact fiber supercontinuum source offers broad vibrational bandwidth with high stability and sufficient power, showing the potential for spectroscopic imaging in a wide range of applications.


Assuntos
Tecnologia de Fibra Óptica/instrumentação , Imagem Molecular/instrumentação , Análise Espectral Raman/instrumentação , Desenho de Equipamento , Análise de Falha de Equipamento , Dinâmica não Linear , Vibração
11.
J Phys Chem A ; 116(25): 6927-34, 2012 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-22646794

RESUMO

Dispersion forces are critical for defining the crystal structures and vibrational potentials of molecular crystals. It is, therefore, important to include corrections for these forces in periodic density functional theory (DFT) calculations of lattice vibrational frequencies. In this study, DFT was augmented with a correction term for London-type dispersion forces in the simulations of the structures and terahertz (THz) vibrational spectra of the dispersion-bound solids naphthalene and durene. The parameters of the correction term were modified to best reproduce the experimental crystal structures and THz spectra. It was found that the accurate reproduction of the lattice dimensions by adjusting the magnitude of the applied dispersion forces resulted in the highest-quality fit of the calculated vibrational modes with the observed THz absorptions. The method presented for the modification of the dispersion corrections provides a practical approach to accurately simulating the THz spectra of molecular crystals, accounting for inherent systematic errors imposed by computational and experimental factors.

12.
Phys Chem Chem Phys ; 14(3): 1113-6, 2012 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-22143120

RESUMO

Solid-state density functional theory can be used for crystal structure determination from powder X-ray diffraction data of molecular crystals that are too large and complex for conventional refinement methods.


Assuntos
Modelos Moleculares , Fenilalanina/química , Cristalografia por Raios X , Conformação Molecular
13.
J Phys Chem A ; 115(50): 14391-6, 2011 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-22107026

RESUMO

Modified cytosine and guanine nucleobases cocrystallize in a hydrogen bonding configuration similar to that observed in native DNA. The noncovalent interactions binding these base pairs in the crystalline solid were investigated using terahertz (THz) spectroscopy and solid-state density functional theory (DFT). While stronger hydrogen bonding interactions are responsible for the general molecular orientations in the crystalline state, it is the weaker dipole-dipole and dispersion forces that determine the overall packing arrangement. The inclusion of dispersion interactions in the DFT calculations was found to be necessary to accurately simulate the unit cell structure and THz vibrational spectrum. Using properly modeled intermolecular potentials, the lattice vibrational motions of the cytosine and guanine derivatives were calculated. The vibrational characters of the modes exhibited by the DNA base pair mimic in the THz region were primarily rotational motions and are indicative of the energies and the nature of vibrations that would likely be observed between similar base pairs in DNA molecules.


Assuntos
Citosina/química , DNA/química , Guanina/química , Pareamento de Bases , Físico-Química , Cristalização , Cristalografia por Raios X , Ligação de Hidrogênio , Modelos Moleculares , Conformação de Ácido Nucleico , Teoria Quântica , Estereoisomerismo , Espectroscopia Terahertz , Vibração
14.
J Phys Chem A ; 115(40): 11039-44, 2011 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-21923096

RESUMO

The terahertz (THz) spectra of crystalline solids are typically uniquely sensitive to the molecular packing configurations, allowing for the detection of polymorphs and hydrates by THz spectroscopic techniques. It is possible, however, that coincident absorptions may be observed between related crystal forms, in which case careful assessment of the lattice vibrations of each system must be performed. Presented here is a THz spectroscopic investigation of citric acid in its anhydrous and monohydrate phases. Remarkably similar features were observed in the THz spectra of both systems, requiring the accurate calculation of the low-frequency vibrational modes by solid-state density functional theory to determine the origins of these spectral features. The results of the simulations demonstrate the necessity of reliable and rigorous methods for THz vibrational modes to ensure the proper evaluation of the THz spectra of molecular solids.


Assuntos
Ácido Cítrico/química , Ácido Cítrico/análogos & derivados , Cristalografia por Raios X , Modelos Moleculares , Espectroscopia Terahertz , Água/química
15.
Anal Chem ; 83(10): 3786-92, 2011 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-21480654

RESUMO

Polymorph detection and quantification in crystalline materials is a principle interest of the pharmaceutical industry. Terahertz (THz) spectroscopy can be used for such analytical applications since this technique is sensitive to the intermolecular interactions of molecules in the solid state. Understanding the fundamental nature of the lattice vibrational motions leading to absorptions in THz spectra is challenging, but may be achieved through computational approaches. In this study, the THz spectra of two diclofenac acid polymorphs were obtained by THz spectroscopy, and the vibrational characters of the observed absorptions were analyzed using solid-state density functional theory (DFT). The results demonstrate the quantitative capacity of THz spectroscopy and the reliability and utility of solid-state DFT in the calculation of low-frequency vibrational motions.


Assuntos
Diclofenaco/análise , Espectroscopia Terahertz/métodos , Cristalografia por Raios X , Diclofenaco/química , Modelos Moleculares , Vibração
16.
J Phys Chem A ; 115(34): 9467-78, 2011 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-21446683

RESUMO

Cocrystallized adenine and thymine derivatives, along with the pure monomeric crystals, were investigated by terahertz spectroscopy and solid-state density functional theory (DFT). The methylated nucleobase derivatives crystallize in planar hydrogen-bonded adenine-thymine pairs similar to the manner found in DNA. The spectra obtained for 1-methylthymine, 9-methyladenine, and the 1:1 cocrystal in the range of 10-100 cm(-1) clearly demonstrate that absorptions in this spectral range originate from the uniquely ordered assembly and the intermolecular interactions found in each individual crystal system. The quality of spectral reproduction for the DFT simulations of each system was clearly improved by the inclusion of an empirical correction term for London-type dispersion forces to the calculations. Notably, it was found that these weak dispersion forces in the adenine-thymine cocrystal were necessary to produce a properly converged crystal structure and meaningful simulation of the terahertz vibrational spectrum.


Assuntos
Adenina/análogos & derivados , Físico-Química , DNA/química , Timina/análogos & derivados , Adenina/análise , Adenina/química , Adenina/metabolismo , Pareamento de Bases , Cristalização , Cristalografia por Raios X , DNA/análise , Ligação de Hidrogênio , Modelos Moleculares , Estereoisomerismo , Espectroscopia Terahertz , Termodinâmica , Timina/análise , Timina/química , Timina/metabolismo , Vibração
17.
Phys Chem Chem Phys ; 13(10): 4250-9, 2011 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-21225035

RESUMO

The effects of applying an empirical dispersion correction to solid-state density functional theory methods were evaluated in the simulation of the crystal structure and low-frequency (10 to 90 cm(-1)) terahertz spectrum of the non-steroidal anti-inflammatory drug, naproxen. The naproxen molecular crystal is bound largely by weak London force interactions, as well as by more prominent interactions such as hydrogen bonding, and thus serves as a good model for the assessment of the pair-wise dispersion correction term in systems influenced by intermolecular interactions of various strengths. Modifications to the dispersion parameters were tested in both fully optimized unit cell dimensions and those determined by X-ray crystallography, with subsequent simulations of the THz spectrum being performed. Use of the unmodified PBE density functional leads to an unrealistic expansion of the unit cell volume and the poor representation of the THz spectrum. Inclusion of a modified dispersion correction enabled a high-quality simulation of the THz spectrum and crystal structure of naproxen to be achieved without the need for artificially constraining the unit cell dimensions.


Assuntos
Anti-Inflamatórios não Esteroides/química , Naproxeno/química , Teoria Quântica , Análise Espectral/métodos , Cristalografia por Raios X , Modelos Moleculares , Conformação Molecular
18.
J Pharm Sci ; 100(3): 1116-29, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-20815081

RESUMO

The potential applications of terahertz (THz) spectroscopy in the analysis of pharmaceutical products in their crystalline state have prompted the need for a more thorough understanding of the fundamental vibrational motions contributing to the THz spectra. The detection of variations in crystal structure and the reliable assignment of observed THz absorption features can be aided by the use of solid-state density functional theory (DFT). In this study, solid-state DFT with periodic boundary conditions was used to simulate the crystalline structure and assign the experimental THz spectra (10-90 cm(-1)) of the enantiomerically pure and racemic forms of the common pharmaceutical compound ibuprofen. The results clearly demonstrate the capabilities of DFT methodologies to accurately reproduce the THz spectra of large complicated molecular systems and provide insight into the internal and external vibrational motions that form the basis of THz spectroscopy.


Assuntos
Ibuprofeno/química , Espectroscopia Terahertz/métodos , Cristalização , Modelos Moleculares , Estrutura Molecular , Software , Estereoisomerismo , Vibração
19.
J Phys Chem A ; 114(35): 9570-8, 2010 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-20715798

RESUMO

The influence of cocrystallized H(2)O molecules on the terahertz (THz) spectra and corresponding computational treatment of hydrated molecular crystals was investigated in the study of protonated and deuterium-substituted l-serine.H(2)O. The THz spectra of both solids have been measured in the range of 10 to 90 cm(-1), with simulations of the crystalline structure and THz vibrational modes performed using solid-state density functional theory. Significant and systematic overestimations of the predicted vibrational frequencies were observed in all calculations. Evidence provided by the comparison of the experimental and calculated vibrational frequencies for both the protonated and deuterated l-serine.H(2)O solids indicates the presence of significant anharmonicity in the observed lattice vibrations. The results suggest that vibrational anharmonicity may play a much larger role in the interpretation of the THz spectra of hydrates in contrast to their corresponding anhydrous forms.


Assuntos
Serina/química , Espectroscopia Terahertz/métodos , Água/química , Cristalografia por Raios X , Ligação de Hidrogênio , Modelos Moleculares , Simulação de Dinâmica Molecular , Estrutura Molecular , Serina/análogos & derivados , Vibração
20.
J Phys Chem A ; 114(26): 7127-38, 2010 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-20536195

RESUMO

Oxalic acid and oxalic acid dihydrate were studied using terahertz spectroscopy and solid-state density functional theory (DFT) in the spectral range 10-100 cm(-1). The size of the oxalic acid molecule and its limited internal degrees of freedom make it ideal for evaluating the performance of computational methods for the structural and dynamical simulation of strongly hydrogen-bonded solids. Calculations of the solid-state structures and terahertz spectra of oxalic acid and oxalic acid dihydrate were performed using the hybrid B3LYP and B3PW91 and the nonhybrid BLYP and PW91 density functionals employing the 6-311G(2d,2p) basis set. When these simulations were compared to the experimental spectra of the oxalic acid solids, a constant overprediction of the dihydrate frequencies was observed in contrast to the results of the anhydrous system. This change in behavior is connected to the nature of the vibrational motions being accessed. The primary molecular motion contributions to the terahertz vibrations of oxalic acid dihydrate were found to originate in the external motions of the cocrystallized H(2)O molecules. The observed overestimation of the vibrational energies in the simulated terahertz spectra is attributed to increased anharmonicity of the vibrational motions in the dihydrate system versus the anhydrous, resulting from weaker hydrogen bonding through the networked water molecules.


Assuntos
Ácido Oxálico/química , Análise Espectral , Água/química , Absorção , Cristalização , Ligação de Hidrogênio , Modelos Moleculares , Conformação Molecular , Teoria Quântica , Análise Espectral Raman , Vibração
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