Anharmonic vibrational probe for N-methylacetamide in different micro-environments

In the present study, anharmonic vibrational properties of the amide modes in N-methylacetamide (NMA), a model molecule for peptide vibrational spectroscopy, are examined by DFT calculations. The 3N-6 normal mode frequencies, diagonal and off-diagonal anharmonicities are evaluated by means of the second order vibrational perturbation theory (VPT2). Good performance of B3LYP/6-31+G** is found for predicting vibrational frequencies in comparison with gas phase experimental data. The amide vibrational modes are assigned through potential energy distribution analysis (PED). The solvation effect on the amide vibrational modes is modeled within the PCM method. From gas phase to polar solvents, red shifts are observed for both harmonic and anharmonic vibrational frequency of amide I mode while the CO bond length increases upon the solvent polarity. Cubic and quartic force constants are further calculated to evaluate the origin of the anharmonicity for the amide I mode of NMA in different micro-environments.     

Vibrational spectroscopic determination of local solvent electric field, solute-solvent electrostatic interaction energy, and their fluctuation amplitudes

IR probes have been extensively used to monitor local electrostatic and solvation dynamics. Particularly, their vibrational frequencies are highly sensitive to local solvent electric field around an IR probe. Here, we show that the experimentally measured vibrational frequency shifts can be inversely used to determine local electric potential distribution and solute-solvent electrostatic interaction energy. In addition, the upper limits of their fluctuation amplitudes are estimated by using the vibrational bandwidths. Applying this method to fully deuterated N-methylacetamide (NMA) in D(2)O and examining the solvatochromic effects on the amide I' and II' mode frequencies, we found that the solvent electric potential difference between O(═C) and D(-N) atoms of the peptide bond is about 5.4 V, and thus, the approximate solvent electric field produced by surrounding water molecules on the NMA is 172 MV/cm on average if the molecular geometry is taken into account. The solute-solvent electrostatic interaction energy is estimated to be -137 kJ/mol, by considering electric dipole-electric field interaction. Furthermore, their root-mean-square fluctuation amplitudes are as large as 1.6 V, 52 MV/cm, and 41 kJ/mol, respectively. We found that the water electric potential on a peptide bond is spatially nonhomogeneous and that the fluctuation in the electrostatic peptide-water interaction energy is about 10 times larger than the thermal energy at room temperature. This indicates that the peptide-solvent interactions are indeed important for the activation of chemical reactions in aqueous solution.     

Simulations of the temperature dependence of amide I vibration

For spectroscopic studies of peptide and protein thermal denaturation it is important to single out the contribution of the solvent to the spectral changes from those originated in the molecular structure. To obtain insights into the origin and size of the temperature solvent effects on the amide I spectra, combined molecular dynamics and density functional simulations were performed with the model N-methylacetamide molecule (NMA). The computations well reproduced frequency and intensity changes previously observed in aqueous NMA solutions. An empirical correction of vacuum frequencies in single NMA molecule based on the electrostatic potential of the water molecules provided superior results to a direct density functional average obtained for a limited number of solute-solvent clusters. The results thus confirm that the all-atom quantum and molecular mechanics approach captures the overall influence of the temperature dependent solvent properties on the amide I spectra and can improve the accuracy and reliability of molecular structural studies.     

Electrostatic DFT map for the complete vibrational amide band of NMA

An anharmonic vibrational Hamiltonian for the amide I, II, III, and A modes of N-methyl acetamide (NMA), recast in terms of the 19 components of an external electric field and its first and second derivative tensors (electrostatic DFT map), is calculated at the DFT(BPW91/6-31G(d,p)) level. Strong correlations are found between NMA geometry and the amide frequency fluctuations calculated using this Hamiltonian together with the fluctuating solvent electric field obtained from the MD simulations in TIP3 water. The amide I and A frequencies are strongly positively correlated with the C=O and N-H bond lengths. The C=O and C-N amide bond lengths are negatively correlated, suggesting the solvent-induced fluctuations of the contribution of zwitterionic resonance form. Sampling the global electric field in the entire region of the transition charge densities (TCDs) is required for accurate infrared line shape simulations. Collective electrostatic solvent coordinates which represent the fluctuations of the 10 lowest amide fundamental and overtone states are reported. Normal-mode analysis of an NMA-3H(2)O cluster shows that the 660 cm(-1) to 1100 cm(-1) oscillation found in the frequency autocorrelation functions of the amide modes may be ascribed to the two bending vibrations of intermolecular hydrogen bonds with the amide oxygen of NMA.     

Amide I vibrational dynamics of N-methylacetamide in polar solvents: the role of electrostatic interactions

The vibrational frequency of the amide I transition of peptides is known to be sensitive to the strength of its hydrogen bonding interactions. In an effort to account for interactions with hydrogen bonding solvents in terms of electrostatics, we study the vibrational dynamics of the amide I coordinate of N-methylacetamide in prototypical polar solvents: D2O, CDCl3, and DMSO-d6. These three solvents have varying hydrogen bonding strengths, and provide three distinct solvent environments for the amide group. The frequency-frequency correlation function, the orientational correlation function, and the vibrational relaxation rate of the amide I vibration in each solvent are retrieved by using three-pulse vibrational photon echoes, two-dimensional infrared spectroscopy, and pump-probe spectroscopy. Direct comparisons are made to molecular dynamics simulations. We find good quantitative agreement between the experimentally retrieved and simulated correlation functions over all time scales when the solute-solvent interactions are determined from the electrostatic potential between the solvent and the atomic sites of the amide group.     

Dependence of amide vibrations on hydrogen bonding

The effect of hydrogen bonding on the amide group vibrational spectra has traditionally been rationalized by invoking a resonance model where hydrogen bonding impacts the amide functional group by stabilizing its [(-)O-C=NH (+)] structure over the [O=C-NH] structure. However, Triggs and Valentini's UV-Raman study of solvation and hydrogen bonding effects on epsilon-caprolactum, N, N-dimethylacetamide (DMA), and N-methylacetamide (NMA) ( Triggs, N. E.; Valentini, J. J. J. Phys. Chem. 1992, 96, 6922-6931) casts doubt on the validity of this model by demonstrating that, contrary to the resonance model prediction, carbonyl hydrogen bonding does not impact the AmII' frequency of DMA. In this study, we utilize density functional theory (DFT) calculations to examine the impact of hydrogen bonding on the C=O and N-H functional groups of NMA, which is typically used as a simple model of the peptide bond. Our calculations indicate that, as expected, the hydrogen bonding frequency dependence of the AmI vibration predominantly derives from the C=O group, whereas the hydrogen bonding frequency dependence of the AmII vibration primarily derives from N-H hydrogen bonding. In contrast, the hydrogen bonding dependence of the conformation-sensitive AmIII band derives equally from both C=O and N-H groups and thus, is equally responsive to hydrogen bonding at the C=O or N-H site. Our work shows that a clear understanding of the normal mode composition of the amide vibrations is crucial for an accurate interpretation of the hydrogen bonding dependence of amide vibrational frequencies.     

Theoretical study of internal field effects on peptide amide I modes

Charged terminal groups or polar side chains of amino acids create spatially nonuniform electrostatic potential around intramolecular peptide bonds and induce amide I mode frequency shifts in polypeptides. By carrying out a series of quantum chemistry calculation studies of various ionic di- and tripeptides as well as dipeptides of 20 different amino acids, these internal field effects on vibrational properties are theoretically investigated. The amide I local and normal mode frequencies and dipole and rotational strengths determining IR and vibrational circular dichroism intensities, respectively, are found to depend on the polar nature of side chains, whereas the vibrational coupling strength weakly does so. The empirical correction and fragment analysis methods were used to theoretically calculate the amide I local mode frequencies and dipole and rotational strengths. These values were directly compared with ab initio and density functional theory calculation results, and the agreements were found to be quantitative.     

Solvent effects on infrared spectra of 2-acetylthiophene in organic solvents

Infrared spectroscopy studies of 2-acetylthiophene (ACTH) in 18 different organic solvents, both polar and non-polar, were undertaken to investigate the solvent-solute interactions. The frequencies of carbonyl stretching vibration upsilon(C=O) of ACTH were correlated with the properties such as the solvent acceptor number (AN) and the linear solvation energy relationships (LSER). The solvent-induced stretching vibration frequency shifts showed a better correlation with the LSER than the AN. A six-membered ring-like hydrogen bonding structure was presented and the solvent effects of ACTH in alcohol solvents were investigated in detail.     

Solvatochromic behavior of donor-acceptor-polyenes: dimethylamino-cyano-diphenylbutadiene

4-(Dimethylamino)-4'-cyano-1,4-diphenylbutadiene (DCB) and 4-(dimethylamino)-2,6-dimethyl-4'-cyano-1,4-diphenylbutadiene (DMDCB) have been characterized spectroscopically. Quantum chemical calculations were performed for comparison. Solvatochromic shifts of the fluorescence were strong and showed a linear dependence on the solvent polarity parameters, whereas shifts in the absorption spectra are very weak only correlate better with the polarizability of the solvents. Excited state dipole moments derived from fluorescence using the Onsager model are very large and similar for both compounds. It is concluded that a strongly allowed and highly dipolar pi, pi* state is the lowest excited state in polar solvents. The strong difference in absorption and fluorescence solvatochromic slopes suggests that the simple Onsager model with a point dipole approximation is not sufficient here.     

Simulation protocols for coherent femtosecond vibrational spectra of peptides

Two algorithms for simulating the response of peptides to sequences of IR pulses are developed and applied to N-methyl acetamide (NMA) and a 17 residue alpha-helical peptide (YKKKH17) in D(2)O. A fluctuating vibrational-exciton Hamiltonian for the amide I mode is constructed from molecular dynamics trajectories. Coupling with the environment is described using a density functional theory electrostatic map. The cumulant expansion of Gaussian fluctuation incorporates motional narrowing due to fast frequency fluctuations and is adequate for NMA and for isotopically labeled bands in large peptides. Real-space truncation of the scattering matrix of the nonlinear exciton equations significantly reduces the computational cost, making it particularly attractive for slow fluctuations in large globular proteins.     

Theory supplemented by experiment. Electronic effects on the rotational stability of the amide group in p-substituted acetanilides

The electronic effect of polar substituents on the barrier of internal rotation around the amide carbon-nitrogen bond in a series of 10 p-substituted acetanilides is studied by applying density functional theory at the B3LYP/6-31G(d,p) level. The theoretical results are supplemented by experimental data on the amide C=O and N-H stretching mode frequency shifts. It is shown that computations at the theoretical level employed provide a valuable approach in studying the factors determining the conformational stability of the studied series of compounds. It is found that an excellent linear dependence between the barriers of rotation and frequency shifts exists. It is concluded that the variations of the amide C=O stretching mode frequency can be used for quantitative characterization of the amide group conformational flexibility in the studied series of acetanilides.     

Ab initio studies of solvent effect on molecular conformation and vibrational spectra of diacetamide

The conformational equilibria and vibrational spectra of diacetamide have been investigated by ab initio molecular orbital studies using the basis sets 6-31g(d,p) and 6-31++g(d,p) at Hartree-Fock and MP2 levels. The vibrational spectra of diacetamide have been satisfactorily interpreted taking into consideration the agreement between the calculated harmonic vibrational frequencies, infrared and Raman band intensities and shifts in deuterated molecules with those observed. The solvent effects were investigated by the self-consistent reaction field (SCRF) theory. The effect of solvent on the conformational equilibria and vibrational spectra is discussed. The calculated changes in the geometry and vibrational spectra on going from the gas phase to the solvent medium are in accord with the increasing weight of the dipolar resonance structure of the amide group in more polar solvents.     

A transferable electrostatic map for solvation effects on amide I vibrations and its application to linear and two-dimensional spectroscopy

A method for modeling infrared solvent shifts using the electrostatic field generated by the solvent is presented. The method is applied to the amide I vibration of N-methyl acetamide. Using ab initio calculations the fundamental frequency, anharmonicity, and the transition dipoles between the three lowest vibrational states are parametrized in terms of the electrostatic field. The generated map, which takes into account the electric field and its gradients at four molecular positions, is tested in a number of common solvents. Agreement of solvent shift and linewidths with experimental Fourier transform infrared (FTIR) data is found to within seven and four wave numbers, respectively, for polar solvents. This shows that in these solvents electrostatic contributions dominate solvation effects and the map is transferable between these types of solvents. The effect of motional narrowing arising from the fast solvent fluctuations is found to be substantial for the FTIR spectra. Also the two-dimensional infrared (2DIR) spectra, simulated using the constructed map, reproduce experimental results very well. The effect of anharmonicity fluctuations on the 2DIR spectra was found to be negligible.     

Understanding the dielectric properties of liquid amides from a polarizable force field

The role played by electronic polarization in the dielectric properties of liquid N-methyl acetamide (NMA) is examined using molecular dynamics simulations with a polarizable force field based on classical Drude oscillators. The model presented is the first force field shown to reproduce the anomalously large dielectric constant of liquid NMA. Details of the molecular polarizability are found to be important. For instance, all elements of the polarizability tensor, rather then just the trace, impact on the condensed phase properties. Two factors related to electronic polarizability are found to contribute to this large dielectric constant. First is the significant enhancement of the mean amide molecular dipole magnitude, which is 50% larger in the liquid than in the gas phase. Second is the consequent strong hydrogen bonding between molecular neighbors that enhances the orientational alignment of the molecular dipoles. Polarizable models of amide compounds that have two (acetamide) and zero (N,N-dimethyl acetamide) polar hydrogen-bond donor atoms are also investigated. Experimentally, the neat liquid dielectric constants at 373 K are 100 for NMA, 66 for acetamide and 26 for N,N-dimethyl acetamide. The polarizable models replicate this trend, predicting a dielectric constant of 92+/-5 for NMA, 66+/-3 for acetamide and 23+/-1 for N,N-dimethyl acetamide.     

UV raman examination of alpha-helical peptide water hydrogen bonding

UV resonance Raman spectra (UVRS) of an alpha-helical, 21 residue, mainly Ala peptide (AP) in the dehydrated solid state were compared to those in aqueous solution at different temperatures. The UVRS amide band frequencies of a dehydrated solid alpha-helix peptide show frequency shifts compared to those in aqueous solution due to the loss of amide backbone hydrogen bonding to water; the amide II and amide III bands of the solid alpha-helix downshift, while the amide I band upshifts. The shifts are identical in direction but smaller than those that occur for alpha-helices in aqueous solution as the temperature increases; water hydrogen bonding strengths decrease as the temperature increases. The UV Raman amide band frequency shifts can be used to monitor alpha-helix hydrogen bonding.     

在酰胺-盐溶剂体系中对苯二甲酰氯与对苯二胺的缩聚反应

本文研究了在酰胺-盐溶剂体系中对苯二胺与对苯二甲酰氯的缩聚反应,溶剂对缩聚反应的影响以及溶剂体系与对苯二甲酰氯的副反应。由NMR实验结果表明,聚对苯二甲酰对苯二胺分子中酰胺基团的氢质子由于溶剂化作用向低场方向位移,位移的大小与溶剂的种类及盐的浓度有关。DMAc与NMP两种溶剂体系在缩聚反应过程中皆与对苯二甲酰氟有竞争反应。在该溶剂体系中可得到适于加工成纤的高分子量聚合物。     

THE PHOTOPHYSICS OF p-AMINOBENZOIC ACID

Abstract— The lowest-lying allowed UV transition in p -aminobenzoic acid (PABA) is assigned Γ→¹L_a based on quantitative absorption and fluorescence studies, as well as semiempirical PM3 multielec-tron configuration interaction calculations. The oscillator strengths, fluorescence quantum efficiencies and lifetimes are reported for PABA in several polar, nonpolar, protic and aprotic solvents (aerated) at 296 K. Reasonable agreement is found between the observed radiative rate constant and that calculated from the absorption and fluorescence spectra. Shifts in the absorption and fluorescence spectra in aprotic solvents are analyzed in terms of the Onsager reaction field model; results are consistent with an increase in dipole moment of ca 4 D between the relaxed S₀ and S₁, states. No evidence is found for the emission from the amino-twisted form of PABA in all solvents studied although calculations show that the amino-twisted S, state is highly polar, but higher in energy by ca 35 kJ/mol ( in vacuo ). The fluorescence efficiency is excitation wavelength independent in both methylcyclohexane and water. The temperature dependence of the nonradiative rate constant (from S₁) was studied in several solvents. Nonradiative decay may be due to intersystem crossing, which would be fast enough to compete with thermally activated intramolecular NH₂ twisting. The phosphorescence spectrum and lifetime obtained in an EPA glass at 77 K are reported, and the triplet energy of PABA is estimated.     

Infrared study of intercomponent interactions in a switchable hydrogen-bonded rotaxane

The macrocycle in rotaxane 1 is preferentially hydrogen bonded to the succinamide station in the neutral form, but can be moved to the naphthalimide station by one-electron reduction of the latter. The hydrogen bonding between the amide NH groups of the macrocycle and the C double bond O groups in the binding stations in the thread was studied with IR spectroscopy in different solvents in both states. In addition, the solvent effect on the vibrational frequencies was analyzed; a correlation with the solvent acceptor number (AN) was observed. The conformational switching upon reduction could be detected by monitoring the hydrogen-bond-induced shifts of the nu(CO) frequencies of the C double bond O groups of the succinamide and the reduced naphthalimide stations. The macrocycle was found to shield the encapsulated station from the solvent: wavenumbers of nu(CO) bands of the C double bond O groups residing inside the macrocycle cavity remain unaffected by the solvent polarity.     

The anharmonic vibrational potential and relaxation pathways of the amide I and II modes of N-methylacetamide

We investigate the influence of isotopic substitution and solvation of N-methylacetamide (NMA) on anharmonic vibrational coupling and vibrational relaxation of the amide I and amide II modes. Differences in the anharmonic potential of isotopic derivatives of NMA in D2O and DMSO-d6 are quantified by extraction of the anharmonic parameters and the transition dipole moment angles from cross-peaks in the two-dimensional infrared (2D-IR) spectra. To interpret the effects of isotopic substitution and solvent interaction on the anharmonic potential, density functional theory and potential energy distribution calculations are performed. It is shown that the origin of anharmonic variation arises from differing local mode contributions to the normal modes of the NMA isotopologues, particularly in amide II. The time domain manifestation of the coupling is the coherent exchange of excitation between amide modes seen as the quantum beats in femtosecond pump-probes. The biphasic behavior of population relaxation of the pump-probe and 2D-IR experiments can be understood by the rapid exchange of strongly coupled modes within the peptide backbone, followed by picosecond dissipation into weakly coupled modes of the bath.