Solvent effects on electronic structures and chain conformations of alpha-oligothiophenes in polar and apolar solutions

Solvent effects on electronic structures and chain conformations of alpha-oligothiophenes nTs (n = 1 to 10) are investigated in solvents of n-hexane, 1,4-dioxane, carbon tetrachloride, chloroform, and water by using density functional theory (DFT) and molecular dynamics (MD) simulations. Both implicit and explicit solvent models are employed. The polarized continuum model (PCM) calculations and MD simulations demonstrate the weak solvent effects on the electronic structures of alpha-oligothiophenes. The lowest dipole-allowed vertical excitation energies of nTs, obtained from time-dependent DFT/PCM calculations at the B3LYP/6-31G(d) level, exhibit a red shift as the solvent polarity increases, in agreement with experiments. The studied solvents have little impact on the state order of the low-lying excited states provided that the nTs are kept in C2h or C2v symmetry. The MD simulations demonstrate that the chain conformations are distorted to some extent in polar and nonpolar solvents. A qualitative picture of the distribution of solvent molecules around the solvated nTs is drawn by means of radial and spatial distribution functions. The S...H-O and pi...H-O solute-solvent interactions are insignificant in aqueous solution.     

Optical rotation calculation of a highly flexible molecule: the case of paraconic acid

The absolute configuration of (S)-(-)-paraconic acid is correctly assigned on the basis of ab initio calculations of the specific optical rotation (OR) at the sodium D line, carried out both in vacuum and in methanol. Density functional theory (DFT) and M?ller-Plesset second-order perturbation theory (MP2) are used to determine the most stable conformational structures, whose OR values are then calculated using DFT linear response theory and London atomic orbitals. The total OR is obtained by averaging these values using the population fractions determined from Boltzmann's statistics. The total OR of the MP2 structures has the correct sign both in vacuum and in solution, whereas only the solvent-relaxed DFT structures correctly reproduce the experimental sign. The strong solvent effect on the total OR is shown to arise primarily due to the variations in the relative energies of the various conformations.     

A joint QM/MD study on α-, β- and γ-cyclodextrins in selective complexation with cathinone

In this article, density functional theory (DFT) calculations and 30 ns molecular dynamic (MD) simulations were performed to investigate the ability of α-, β- and γ-cyclodextrins (CDs) to form selective complexes with cathinone. DFT calculations in the gas phase, water, chloroform and methanol reveal that the solvents, reduce the stability of the complexes. Optimized structures confirm that α-CD cannot encapsulate cathinone, completely, while other CDs showed an opposite behavior. DFT calculations indicate that cathinone has the most stable complex with γ-CD in comparison to the α- and β-CDs. Natural bond orbital and quantum theory of atoms in molecules analyses reveal that the electrostatic interactions between cathinone and CDs are the driving force of the complex formation. MD simulations confirm that different solvents play an important role in the stability of the cathinone complexes and the obtained MD results are in good agreement with the DFT calculations.     

Hybrid QM/MM simulation of the hydration phenomena of dipalmitoylphosphatidylcholine headgroup

The polar headgroup of dipalmitoylphosphatidylcholine (DPPC) molecule both in gas phase and aqueous solution is investigated by the hybrid quantum mechanical/molecular mechanical (QM/MM) method, in which the polar head of DPPC molecule and the bound water molecules are treated with density functional theory (DFT), while the apolar hydrocarbon chain of DPPC molecule is treated with MM method. It is demonstrated that the hybrid QM/MM method is both accurate and efficient to describe the conformations of DPPC headgroup. Folded structures of headgroup are found in gas phase calculations. In this work, both monohydration and polyhydration phenomena are investigated. In monohydration, different water association sites are studied. Both the hydration energy and the quantum properties of DPPC and water molecules are calculated at the DFT level of theory after geometry optimization. The binding force of monohydration is estimated by using the scan method. In polyhydration, more extended conformations are found and hydration energies in different polyhydration styles are estimated.     

Synthesis, spectroscopic characterizations and quantum chemical computational studies of (Z)-4-[(E)-(4-fluorophenyl)diazenyl]-6-[(3-hydroxypropylamino)methylene]-2-methoxycyclohexa-2,4-dienone

In this study, the molecular structure and spectroscopic properties of the title compound were characterized by X-ray diffraction, FT-IR and UV-vis spectroscopies. These properties were also investigated using DFT method. The most convenient conformation of title compound was firstly determined. The geometry optimizations in gas phase and solvent media were performed by DFT methods with B3LYP adding 6-31G(d) basis set. The differences between crystal and computational structures are due to crystal packing in which hydrogen bonds play an important role. UV-vis spectra were recorded in different organic solvents. The results show that title compound exists in both keto and enol forms in DMSO, EtOH but it tends to shift towards enol form in benzene. The polar solvents facilitate the proton transfer by decreasing the activation energy needed for Transition State. The formation of both keto and enol forms in DMSO and EtOH is due to decrease in the activation energy. TD-DFT calculations starting from optimized geometry were carried out in both gas and solution phases to calculate excitation energies of the title compound. The non-linear optical properties were computed at the theory level and the title compound showed a good second order non-linear optical property. In addition, thermodynamic properties were obtained in the range of 100-500K.     

Exploring the dynamics of calix[4]pyrrole: effect of solvent and fluorine substitution

Molecular dynamics simulations show that calix[4]pyrrole (CP) and octafluorocalix[4]pyrrole (8F-CP) are extremely flexible molecules. CP mainly adopts the 1,3-alternate conformation in all the solvents, although the percentage of alternative conformations increases in polar solvents, especially those with good hydrogen-bonding acceptor properties. However, in the case of 8F-CP, the cone conformation is the most populated in some solvents. Transitions between conformers are common and fast, and both CP and 8F-CP can adopt the cone conformation needed for optimum interaction with anions more easily than would be predicted on the basis of previous gas-phase calculations. Furthermore, the present studies show that when a fluoride anion is specifically placed initially in close proximity to CP and 8F-CP in their respective 1,3-alternate conformations, an extremely fast change to the cone conformation is observed in both cases. The results suggest that preorganization does not represent a major impediment to anion-binding for either CP or 8F-CP, and that ion-induced conformational changes can follow different mechanisms depending on the solvent and the chemical substituents present on the calix[4]pyrrole beta-pyrrolic positions.     

Spin states at a tipping point: what determines the dz2(1) ground state of nickel(III) tetra(tbutyl)porphyrin dicyanide?

Density functional theory (DFT) calculations, regardless of the exchange-correlation functional, have long failed to reproduce the observed dz2(1) ground state of the [NiIII(TtBuP)(CN)2]- anion (where TtBuP is the strongly ruffled tetra(tbutyl)porphyrin ligand), predicting instead a dx2-y2(1) ground state. Normally, such failures are associated with DFT calculations on spin states of different multiplicity, which is not the case here. The calculations reported here strongly suggest that the problem does not lie with DFT. Instead environmental factors need to be taken into account, such as counterions and solvents. Counterions such as K+ placed against the cyanide nitrogens and polar solvents both result in a dz2(1) ground state, thus finally reconciling theory and experiment.     

Proline-based chiral stationary phases: a molecular dynamics study of the interfacial structure

Proline chains have generated considerable interest as a possible basis for new selectors in chiral chromatography. In this article, we employ molecular dynamics simulations to examine the interfacial structure of two diproline chiral selectors, one with a terminal trimethylacetyl group and one with a terminal t-butyl carbamate group. The solvents consist of a relatively apolar n-hexane/2-propanol and a polar water/methanol mixture. We begin with electronic structure calculations for the two chiral selectors to assess the energetics of conformational changes, particularly along the backbone where the amide bonds can alternate between cis and trans conformations. Force fields have been developed for the two selectors, based on these ab initio calculations. Molecular dynamics simulations of the selective interfaces are performed to examine the preferred backbone conformations, as a function of end-group and solvent. The full chiral surface includes the diproline selectors, trimethylsilyl end-caps, and silanol groups. Connection is made with selectivity measurements on these interfaces, where significant differences are observed between these two very similar selectors.     

Secondary fluorescences of 4'-(1-pyrenyl)acetophenone and p-dimethylaminoacetophenone

4'-(1-Pyrenyl)acetophenone (PYRA) and p-dimethylaminoacetophenone (DMAA) were investigated in nonpolar and polar protic and aprotic solvents over a wide temperature range. Quantum chemical (INDO/S) calculations of the energies of electronic transitions, oscillator strengths and dipole moments were performed for planar and twisted conformations of both compounds. For DMAA, the experimental results are well explained in terms of the TICT state. In the case of PYRA in polar aprotic solvents, two alternative models are discussed: TICT state formation or inversion of the two low lying singlet states.     

Conformation-specific spectroscopy of 4-phenyl-1-butyne and 5-phenyl-1-pentyne

4-Phenyl-1-butyne and 5-phenyl-1-pentyne were studied by a combination of methods including resonance-enhanced-two-photon ionization, UV-UV hole-burning spectroscopy, and rotational band contour studies. There are two conformations of 4-phenyl-1-butyne observed in the expansion with their S1<-- S0 origins occurring at 37617 and 37620 cm(-1). MP2 and DFT calculations identify these two low energy conformations (with the acetylenic group anti or gauche with respect to the ring) and confirm that these are the only two low energy conformations anticipated to have population in them. The experimental rotational band contours of the origin bands were compared to simulations based on transition moment directions and rotational constants predicted by CIS calculations. This comparison leads to definitive assignments for the bands, with the gauche and anti conformations assigned to the red and blue-shifted conformers, respectively. Three conformations of 5-phenyl-1-pentyne were observed in the expansion with their S1<-- S0 origins occurring at 37538, 37578, and 37601 cm(-1). MP2 and DFT calculations predict four low energy structures arising from gauche or anti conformations about each of the Calpha-Cbeta and Cbeta-Cgamma bonds. Rotational band contour analysis was used to assign the above transitions to gauche-anti (ga), gauche-gauche (gg), and anti-gauche (ag) structures, respectively.     

An ab initio SCF study on the tautomerisation of the 8-oxo-guanine and xanthine

All possible H₉-tautomers of 8-oxo-guanine and xanthine were studied by means of PM3 semiempirical and DFT (density functional theory) quantum chemistry methods. Additionally, the five most stable tautomers of both guanine derivatives were estimated on 3-21G, 6-31G, 6-31G^** and MP2 (6-31G^**) ab initio levels. The impact of the environment polarity on the tautomeric equilibrium was also taken into account. Among the variety of tautomeric isomers most probable are diketo forms of both studied derivatives in non-polar and polar surroundings.

The tautomeric equilibrium was unchanged after connection of the sugar backbone. The most preferred diketo forms of 8-oxo-guanosine and xanthidine are in syn conformations both in polar and non-polar environments. The increase of the syn conformations over anti ones may have the source in the formation of the internal hydrogen bonds between H′5 and N₃ atoms. The calculated values of the pseudorotation phase angle were between 144 and 180° in all cases. This corresponds to C′2-endo conformations of all optimised structures.

The N-glycosidic bond stability of most stable tautomers was compared to standard guanosine. Most tautomers of 8-oxo-guanosine and xanthidine are characterised by more stable C₁′-N₉ bond. This indicates that both these derivatives are hardly susceptible to spontaneous depurination and its removal from the DNA will depend mostly on the activity of DNA repair enzymes.     

Tautomerism in 7-hydroxyquinoline: a combined experimental and theoretical study in water

Tautomerism in the ground and excited states of 7-hydroxyquinoline (7HQ) was studied in different solvents using steady-state and lifetime spectroscopic measurements, density functional theory (DFT) calculations, and molecular dynamics (MD) simulations. Equilibrium between the enol and the keto/zwitterion tautomers exists in 7HQ, which is solvent-dependent. Of the solvents used in this study, only in water does the absorbance spectrum of 7HQ show absorption from both the enol and zwitterion tautomers. In addition, in aqueous media, fluorescence is observed from the zwitterion tautomer only, which is attributed to self-quenching of the enol fluorescence by energy transfer to the ground-state zwitterion tautomer and energetically favorable excited-state proton transfer. Solvation of the hydrogen bonding sites of 7HQ was studied in binary mixtures of 1,4-dioxane and water, and three water molecules were estimated to connect the polar sites and induce intermolecular proton transfer. The results are confirmed by DFT calculations showing that three water molecules are the minimum number required to form a stable solvent wire. Mapping the water density around the polar sites using MD simulations shows well-defined hydrogen bonds around the amino and hydroxyl groups of the enol tautomer and slightly less well-defined hydrogen bonds for the zwitterion tautomer. The presence of three-member water wires connecting the polar centers in 7HQ is evident in the MD simulations. The results point to the unique spectral signatures of 7HQ in water, which make this molecule a potential probe to detect the presence of water in nanocavities of macromolecules.     

Helical molecular programming: folding of oligopyridine-dicarboxamides into molecular single helices

Molecular strands composed of alternating 2,6-diaminopyridine and 2,6-pyridinedicarbonyl units have been designed to self-organize into single stranded helical structures upon forming intramolecular hydrogen bonds. Pentameric strands 11, 12, and 14, heptameric strands 1 and 20, and undecameric strand 15 have been synthesized using stepwise convergent strategies. Single helical conformations have been characterized in the solid state by single crystal X-ray diffraction analysis for four of these compounds. Helices from pentameric strands 12 and 14 extend over one turn, and helices from heptameric 20 and undecameric 15 species extend to one and a half and two and a half turns, respectively. Intramolecular hydrogen bonds are responsible for the strong bending of the strands. 1H NMR shifts both in polar and nonpolar organic solvents indicate intramolecular overlap between the peripheral aromatic groups. Thus, helical conformations also predominate in solution. Molecular stochastic dynamic simulations of strand folding starting from a high energy extended linear conformer show a rapid (600 ps at 300 K) conversion into a stable helical conformation.     

Continuum treatment of electronic polarization effect

A continuum treatment of electronic polarization has been explored for in molecular mechanics simulations in implicit solvents. The dielectric constant for molecule interior is the only parameter in the continuum polarizable model. A value of 4 is found to yield optimal agreement with high-level ab initio quantum mechanical calculations for the tested molecular systems. Interestingly, its performance is not sensitive to the definition of molecular volume, in which the continuum electronic polarization is defined. In this model, quantum mechanical electrostatic field in different dielectric environments from vacuum, low-dielectric organic solvent, and water can be used simultaneously in atomic charge fitting to achieve consistent treatment of electrostatic interactions. The tests show that a single set of atomic charges can be used consistently in different dielectric environments and different molecular conformations, and the atomic charges transfer well from training monomers to tested dimers. The preliminary study gives us the hope of developing a continuum polarizable force field for more consistent simulations of proteins and nucleic acids in implicit solvents.     

Study of the formamide–methanol dimer with ab initio and density functional theory methods

For the first time, the structures and energies for the hydrogen bonding of a 1:1 complex formed between formamide and methanol molecules have been computed with various pure and hybrid density functional theory (DFT) and ab initio methods at varied basis set levels from 6‐31g to 6‐31+g(d,p). Five reasonable geometries on the potential energy surface of methanol and formamide system are considered and their relative stability is discussed. The infrared (IR) spectrum frequencies, IR intensities, and vibrational frequency shifts are reported. From the systematic studies, it is found that all the DFT methods selected here correctly compute the dimerization energies and geometries, with the B3P86 method predicting the hydrogen bond lengths relatively shorter and BPW91 yielding the interaction energies relatively lower. Finally, the solvent effects on the geometries of the formamide–methanol complexes have also been investigated using self‐consistent reaction field (SCRF) calculations with five different DFT methods at the 6‐31+g(d,p) basis set level. The results indicate that the polarity of the solvent has played an important role on the structures and relative stabilities of different isomers. Moreover, the basis set superposition error correction is critical to the interaction energies in the polar solvents. © 2003 Wiley Periodicals, Inc. Int J Quantum Chem, 2004     

Theoretical studies of the solvent effect on the conformation of the HO-C-C-X (X = F, NH2, NO2) moiety with competing intra- and intermolecular hydrogen bonds

Theoretical calculations up to the ab initio IEF-PCM/CCSD(T)/CBS//IEF-PCM/B3LYP/6-311++G** and IEF-PCM/B97D/aug-cc-pvtz levels have been performed for 2X-ethanol and 2X-phenol systems with X = F, NH(2), NO(2) in chloroform and aqueous solution. The calculated relative free energies by means of the IEF-PCM continuum dielectric method do not differ very much at the DFT and ab initio levels. Application of explicit solvent models and the FEP/MC method for determining relative solvation free energies causes, however, large deviations in the predicted equilibrium compositions, although the predominant conformation for the solute is generally in agreement with that from the corresponding IEF-PCM calculations. Existence of an intramolecular hydrogen bond (HB structure) for species with the HO-C-C-X moiety is preferred compared with a conformation when the hydrogen bond is disrupted (NoHB) for the considered F- and NO(2)-substituted molecules both in chloroform and aqueous solution. For 2NH(2)-ethanol, the HB structure is predominant in chloroform, whereas the 93:7 ratio for the OCCN trans/gauche species was obtained in aqueous solution. 2NH(2)-phenol exhibits a subtle equilibrium of the HB and NoHB conformations in both solvents. Potential of mean force calculations predict about a 10% solute association for the trans 2NH(2)-ethanol solute even in the fairly dilute 0.22 molar solution, whereas direct MC simulations do not support the maintenance of a doubly hydrogen-bonded dimer. Aqueous solution characteristics, as coordination numbers and numbers of strongly bound water molecules to the solute at T = 298 K and p = 1 atm, correspond reasonably to the derived molecular structures.     

All‐Atom Molecular Dynamics Simulation of Structure and Diffusion of Hydrophilic Antistatic Agents in Polypropylene

Glycerol monostearate (GMS) is an additive widely used in plastic industry for its good ability to improve the wettability and antistatic property of polymer surfaces. Based on GMS, we propose five additives of different polarity by attuning the number of oxyethyl groups. All‐atom molecular dynamics simulations of these additives in polypropylene (PP) matrix are carried out at temperatures of 300 K, 350 K and 400 K. Detailed molecular conformations are obtained and analyzed. Due to the gauche effect of the dihedral angles, the polar parts of these additives form helix structures. The diffusion coefficient of the additives depends on their molecular conformations and decreases monotonously with increasing polarity. These results are expected to be helpful in rational design of hydrophilic antistatic agents in polymeric materials.     

Quantum mechanical calculations of tryptophan and comparison with conformations in native proteins

We report a detailed analysis of the potential energy surface of N-acetyl-l-tryptophan-N-methylamide, (NATMA) both in the gas phase and in solution. The minima are identified using the density-functional-theory (DFT) with the 6-31g(d) basis set. The full potential energy surface in terms of torsional angles is spanned starting from various initial configurations. We were able to locate 77 distinct L-minima. The calculated energy maps correspond to the intrinsic conformational propensities of the individual NATMA molecule. We show that these conformations are essentially similar to the conformations of tryptophan in native proteins. For this reason, we compare the results of DFT calculations in the gas and solution phases with native state conformations of tryptophan obtained from a protein library. In native proteins, tryptophan conformations have strong preferences for the beta sheet, right-handed helix, tight turn, and bridge structures. The conformations calculated by DFT, the solution-phase results in particular, for the single tryptophan residue are in agreement with native state values obtained from the Protein Data Bank.     

Is Poisson-Boltzmann theory insufficient for protein folding simulations?

The Poisson-Boltzmann theory has been widely used in the studies of energetics and conformations of biological macromolecules. Recently, introduction of the efficient generalized Born approximation has greatly extended its applicability to areas such as protein folding simulations where highly efficient computation is crucial. However, limitations have been found in the folding simulations of a well-studied beta hairpin with several generalized Born implementations and different force fields. These studies have raised the question whether the underlining Poisson-Boltzmann theory, on which the generalized Born model is calibrated, is adequate in the treatment of polar interactions for the challenging protein folding simulations. To address the question whether the Poisson-Boltzmann theory in the current formalism might be insufficient, we directly tested our efficient numerical Poisson-Boltzmann implementation in the beta-hairpin folding simulation. Good agreement between simulation and experiment was found for the beta-hairpin equilibrium structures when the numerical Poisson-Boltzmann solvent and a recently improved generalized Born solvent were used. In addition simulated thermodynamic properties also agree well with experiment in both solvents. Finally, an overall agreement on the beta-hairpin folding mechanism was found between the current and previous studies. Thus, our simulations indicate that previously observed limitations are most likely due to imperfect calibration in previous generalized Born models but not due to the limitation of the Poisson-Boltzmann theory.