Conformational landscape of (R,R)-pterocarpans with biological activity in vacuo and in aqueous solution (PCM and/or water clusters)

All possible combinations of stable dihedral values have been considered in vacuo at the B3LYP/6-31G level for 3,9-dihydroxy-4,8-diprenylpterocarpan (erybraedin C), whose hydroxy out-out conformation had been examined earlier together with the conformational preferences of 3,9-dimethoxy-4-prenylpterocarpan (bitucarpin A) at the same level (Phys. Chem. Chem. Phys. 2004, 6, 2849). The structure with O5 trans with respect to H6a (O(t)) is about 2 kcal/mol less stable in vacuo than that with one of the H6 trans to it (H(t)); in aqueous solution its energy gap is nearly conserved. The in-in arrangement of the hydroxyl groups of erybraedin turns out to be preferred in vacuo (even considering zero point and thermal effects), where pseudo H-bonds are formed between hydroxy hydrogens and pi electron distributions of prenyl groups. The continuum solvent effect (water) at the IEF-PCM/B3LYP/6-31G level on the relative stability of the various rotamers is very limited both on bitucarpin and erybraedin. Considering the dihydrated derivatives, significant differences in the solvation energy are found between the distinct hydration sites, increasing in the order: methoxy O, ring O, hydroxy O, and hydroxy H. In hydroxy-water interactions, in fact, water prefers to behave as an H-bond acceptor unless nearby bulky groups prevent its approach. Interestingly enough, a bridging water molecule between the hydroxy H of erybraedin and the prenyl group can be found. The inclusion of BSSE corrections in hydroxy-water interactions decidedly favors out-out hydrated arrangements, followed by out-in and in-out ones. Bulk solvent effects with IEF-PCM about the dihydrated systems almost invert the stability order found in vacuo. When a four-water cluster is considered using QM methods, waters gather in H-bonded pairs around the solute OH groups. MD simulations, carried out on a pterocarpan solute (J. Phys. Chem. B 2005, 109, 16918), supply water adducts consistent with a liquid state that have also been embedded in the continuum solvent.     

Excluded volume effect for large and small solutes in water

The cavitation effect, i.e., the process of the creation of a void of excluded volume in bulk solvent (a cavity), is considered. The cavitation free energy is treated in terms of the information theory (IT) approach [Hummer, G.; Garde, S.; Garcia, A. E.; Paulaitis, M. E.; Pratt, L. R. J. Phys. Chem. B 1998, 102, 10469]. The binomial cell model suggested earlier is applied as the IT default distribution p(m) for the number m of solute (water) particles occupying a cavity of given size and shape. In the present work, this model is extended to cover the entire range of cavity size between small ordinary molecular solutes and bulky biomolecular structures. The resulting distribution consists of two binomial peaks responsible for producing the free energy contributions, which are proportional respectively to the volume and to the surface area of a cavity. The surface peak dominates in the large cavity limit, when the two peaks are well separated. The volume effects become decisive in the opposite limit of small cavities, when the two peaks reduce to a single-peak distribution as considered in our earlier work. With a proper interpolation procedure connecting these two regimes, the MC simulation results for model spherical solutes with radii increasing up to R = 10 A [Huang, D. H.; Geissler, P. L.; Chandler, D. J. Phys. Chem. B 2001, 105, 6704] are well reproduced. The large cavity limit conforms to macroscopic properties of bulk water solvent, such as surface tension, isothermal compressibility and Tolman length. The computations are extended to include nonspherical solutes (hydrocarbons C1-C6).     

Long-range proton transfer in aqueous Acid-base reactions

We study the mechanism of proton transfer (PT) in the aqueous acid-base reaction between the photoacid 8-hydroxy-1,3,6-pyrenetrisulfonic acid (HPTS) and acetate by probing the vibrational resonances of HPTS, acetate, and the hydrated proton with femtosecond mid-infrared laser pulses. We find that PT takes place in a distribution of hydrogen-bound reaction complexes that differ in the number of water molecules separating the acid and the base. The number of intervening water molecules ranges from 0 to 5, which, together with a strongly distance-dependent PT rate, explains the observed highly nonexponential reaction kinetics. The kinetic isotope effect for the reaction is determined to be 1.5, indicating that tunneling does not play a significant role in the transfer of the proton. Rather, the transfer mechanism is best described in terms of the adiabatic PT picture as it has been formulated by Hynes and co-workers [Staib, A.; Borgis, D.; Hynes, J. T. J. Chem. Phys. 1995, 102, 2487. Ando, K.; Hynes, J. T. J. Phys. Chem. B 1997, 101, 10464.], where solvent fluctuations play an essential role in forming the correct hydrogen-bond configuration and solvent polarization to facilitate PT.     

Design of surface active soluble peptide molecules at the air/water interface

Surface active molecules collect at interfaces and have the potential to be used for water evaporation reduction. The objective of this work is to design surface active soluble peptides that collect at the air/water interface using molecular simulations. Rotational isomeric state Monte Carlo (RISMC) sampling together with a solvation model that we recently invented, the AAD solvation model [Gu, C.; Lustig, S.; Trout, B. J. Phys. Chem. B 2006, 110 (3), 1476-1484] was applied to calculate the adsorption free energy of the peptide molecule at the air/water interface. The results were validated by both molecular dynamics simulations with an explicit solvent model and surface tension measurements on synthesized peptides. It was demonstrated that this approach is able to give a reasonable prediction of surface activity with an approximately 50% hit rate in terms of designed surface active molecules actually being surface active. The relationship between the chemical composition and the surface morphology is also discussed.     

The ionic work function and its role in estimating absolute electrode potentials

The experimental determination of the ionic work function is briefly described. Data for the proton, alkali metal ions, and halide ions in water, originally published by Randles (Randles, J. E. B. Trans Faraday Soc. 1956, 52, 1573) are recalculated on the basis of up-to-date thermodynamic tables. These calculations are extended to data for the same ions in four nonaqueous solvents, namely, methanol, ethanol, acetonitrile, and dimethyl sulfoxide. The ionic work function data are compared with estimates of the absolute Gibbs energy of solvation obtained by an extrathermodynamic route for the same ions. The work function data for the proton are used to estimate the absolute potential of the standard hydrogen electrode in each solvent. The results obtained here are compared with those published earlier by Trasatti (Trasatti, S. Electrochim. Acta 1987, 32, 843) and more recently by Kelly et al. (Kelly, C. P.; Cramer, C. J.; Truhlar, D. G. J. Phys. Chem. B 2006, 110, 16066. Kelly, C. P.; Cramer, C. J.; Truhlar, D. G. J. Phys. Chem. B 2007, 111, 408). A comparison of the ionic work function with the absolute Gibbs solvation energy permits an estimation of the surface potential of the solvent. The results show that the surface potential of water is small and positive whereas the surface potential of the nonaqueous solvents considered is negative. The sign of the surface potential is consistent with the known structure of each solvent.     

Molecular dynamics simulation of the energetic room-temperature ionic liquid, 1-hydroxyethyl-4-amino-1,2,4-triazolium nitrate (HEATN)

Molecular dynamics (MD) simulations have been performed to investigate the structure and dynamics of an energetic ionic liquid, 1-hydroxyethyl-4-amino-1,2,4-triazolium nitrate (HEATN). The generalized amber force field (GAFF) was used, and an electronically polarizable model was further developed in the spirit of our previous work (Yan, T.; Burnham, C. J.; Del Popolo, M. G.; Voth, G. A. J. Phys. Chem. B 2004, 108, 11877). In the process of simulated annealing from a liquid state at 475 K down to a glassy state at 175 K, the MD simulations identify a glass-transition temperature region at around 250-275 K, in agreement with experiment. The self-intermediate scattering functions show vanishing boson peaks in the supercooled region, indicating that HEATN may be a fragile glass former. The coupling/decoupling of translational and reorientational ion motion is also discussed, and various other physical properties of the liquid state are intensively studied at 400 K. A complex hydrogen bond network was revealed with the calculation of partial radial distribution functions. When compared to the similarly sized 1-ethyl-4-methyl-1,4-imidazolium nitrate ionic liquid, EMIM+/NO3-, a hydrogen bond network directly resulting in the poorer packing efficiency of ions is observed, which is responsible for the lower melting/glass-transition point. The structural properties of the liquid/vacuum interface shows that there is vanishing layering at the interface, in accordance with the poor ion packing. The effects of electronic polarization on the self-diffusion, viscosity, and surface tension of HEATN are found to be significant, in agreement with an earlier study on EMIM+/NO3- (Yan, T.; Burnham, C. J.; Del Popolo, M. G.; Voth, G. A. J. Phys. Chem. B 2004, 108, 11877).     

VBSM: a solvation model based on valence bond theory

A new solvation model, called VBSM, is presented. The model combines valence bond (VB) theory with parameters determined for the SM6 solvation model (Kelly, C. P.; Cramer, C. J.; Truhlar, D. G. J. Chem. Theo. Comp. 2005, 1, 1133-1152). VBSM, like SM6, is based on the generalized Born (GB) approximation for bulk electrostatics and atomic surface tensions to account for cavitation, dispersion, and solvent structure (CDS). The solvation free energy of VBSM includes (i) a self-consistent polarization term obtained by using VB atomic charges in a GB reaction field with a VB self-consistent field procedure that minimizes the total energy of the system with respect to the valence bond orbitals and (ii) a geometry-dependent CDS term to account for deviations from bulk-electrostatic solvation. Test calculations for a few systems show that the liquid-phase partial atomic charges obtained by VBSM are in good agreement with liquid-phase charges obtained by charge model CM4 (Kelly, C. P.; Cramer, C. J.; Truhlar, D. G. J. Chem. Theo. Comp. 2005, 1, 1133-1152). Free energies of solvation are calculated for two prototype test cases, namely, for the degenerate S(N)2 reaction of Cl(-) with CH(3)Cl in water and for a Menshutkin reaction in water. These calculations show that the VBSM method provides a practical alternative to single-configuration self-consistent field theory for solvent effects in molecules and chemical reactions.     

Role of hydration in determining the structure and vibrational spectra of L-alanine and N-acetyl L-alanine N′-methylamide in aqueous solution: a combined theoretical and experimental approach

In this work we have utilized recent density functional theory Born-Oppenheimer molecular dynamics simulations to determine the first principles locations of the water molecules in the first solvation shell which are responsible for stabilizing the zwitterionic structure of L-alanine. Previous works have used chemical intuition or classical molecular dynamics simulations to position the water molecules. In addition, a complete shell of water molecules was not previously used, only the water molecules which were thought to be strongly interacting (H-bonded) with the zwitterionic species. In a previous work by Tajkhorshid et al. (J Phys Chem B 102:5899) the L-alanine zwitterion was stabilized by 4 water molecules, and a subsequent work by Frimand et al. (Chem Phys 255:165) the number was increased to 9 water molecules. Here we found that 20 water molecules are necessary to fully encapsulate the zwitterionic species when the molecule is embedded within a droplet of water, while 11 water molecules are necessary to encapsulate the polar region with the methyl group exposed to the surface, where it migrates during the MD simulation. Here we present our vibrational absorption, vibrational circular dichroism and Raman and Raman optical activity simulations, which we compare to the previous simulations and experimental results. In addition, we report new VA, VCD, Raman and ROA measurements for L-alanine in aqueous solution with the latest commercially available FTIR VA/VCD instrument (Biotools, Jupiter, FL, USA) and Raman/ROA instrument (Biotools). The signal to noise of the spectra of L-alanine measured with these new instruments is significantly better than the previously reported spectra. Finally we reinvestigate the causes for the stability of the P_π structure of the alanine dipeptide, also called N-acetyl-L-alanine N′-methylamide, in aqueous solution. Previously we utilized the B3LYP/6-31G* + Onsager continuum level of theory to investigate the stability of the NALANMA4WC Han et al. (J Phys Chem B 102:2587) Here we use the B3PW91 and B3LYP hybrid exchange correlation functionals, the aug-cc-pVDZ basis set and the PCM and CPCM (COSMO) continuum solvent models, in addition to the Onsager and no continuum solvent model. Here by the comparison of the VA, VCD, Raman and ROA spectra we can confirm the stability of the NALANMA4WC due to the strong hydrogen bonding between the four water molecules and the peptide polar groups. Hence we advocate the use of explicit water molecules and continuum solvent treatment for all future spectral simulations of amino acids, peptides and proteins in aqueous solution, as even the structure (conformer) present cannot always be found without this level of theory. Festschift in Honor of Philip J. Stephens’ 65th Birthday. During the proof stage of this article a very relevant article has been published by M. Losada and Y. Xu titled “Chirality transfer through hydrogen-bonding: Experimental and ab initio analyses of vibrational circular dichroism spectra of methyl lactate in water” in Phys Chem Chem Phys 2007, 9: 3127–3135. In that work they confirm that the effects of water are seen in the VCD spectra and hence it is fundamental to include explicit water molecules in modeling studies of the vibrational spectra of biomolecules in aqueous solution.     

Mixed atomistic and coarse-grained molecular dynamics: simulation of a membrane-bound ion channel

The recently developed multiscale coarse-graining (MS-CG) method (Izvekov, S.; Voth, G. A. J. Phys. Chem. B 2005, 109, 2469; J. Chem. Phys. 2005, 123, 134105) is used to build a mixed all-atom and coarse-grained (AA-CG) model of the gramicidin A (gA) ion channel embedded in a dimyristoylphosphatidylcholine (DMPC) lipid bilayer and water environment. In this model, the gA peptide was described in full atomistic detail, while the lipid and water molecules were described using coarse-grained representations. The atom-CG and CG-CG interactions in the mixed AA-CG model were determined using the MS-CG method. Molecular dynamics (MD) simulations were performed using the resulting AA-CG model. The results from simulations of the AA-CG model compare very favorably to those from all-atom MD simulations of the entire system. Since the MS-CG method employs a general and systematic approach to obtain effective interactions from the underlying all-atom models, the present approach to rigorously develop mixed AA-CG models has the potential to be extended to many other systems.     

Equation of state for the phase coexistence region of insoluble monolayers under consideration of the entropy nonideality

The equation of state for the monolayer with a fluid (G, LE)/condensed (LC) phase transition derived earlier (Fainerman, V.B.; Vollhardt, D. J. Phys. Chem. B 1999, 103, 145) in the framework of a quasichemical approach is generalized. A term is added that takes into account the entropy nonideality of mixing of the monomers and clusters of amphiphilic molecules. The results calculated from the proposed equations agree well with the experimental Pi-A isotherms obtained for various types of amphiphilic monolayers. The values of molecular areas of the amphiphilic molecules estimated from the fitting of experimental data to the proposed equation are quite similar to the real values. Another equation of state capable of describing the fluid state of insoluble monolayers and based on equations for the chemical potential of the solvent in the bulk phase and in the surface layer (Fainerman, V. B.; Vollhardt, D. J. Phys. Chem. B 2006, 110, 10436) is also generalized to be extended to the fluid/condensed phase transition region (A < A(c)), taking into account entropy nonideality for mixing solvent molecules, monomers, and clusters of amphiphilic molecules. The values calculated on this basis agree also well with the experimental data.     

Molecular insights into the heterogeneous crystal growth of si methane hydrate

In this paper we report a successful molecular simulation study exploring the heterogeneous crystal growth of sI methane hydrate along its [001] crystallographic face. The molecular modeling of the crystal growth of methane hydrate has proven in the past to be very challenging, and a reasonable framework to overcome the difficulties related to the simulation of such systems is presented. Both the microscopic mechanisms of heterogeneous crystal growth as well as interfacial properties of methane hydrate are probed. In the presence of the appropriate crystal template, a strong tendency for water molecules to organize into cages around methane at the growing interface is observed; the interface also demonstrates a strong affinity for methane molecules. The maximum growth rate measured for a hydrate crystal is about 4 times higher than the value previously determined for ice I in a similar framework (Gulam Razul, M. S.; Hendry, J. G.; Kusalik, P. G. J. Chem. Phys. 2005, 123, 204722).     

Calculated and experimental NMR chemical shifts of p-menthane-3,9-diols. A combination of molecular dynamics and quantum mechanics to determine the structure and the solvent effects

NMR chemical shifts have been experimentally measured and theoretically estimated for all the carbon atoms of (1R,3S,4S,8S)-p-menthane-3,9-diol in chloroform solution. Theoretical estimations were performed using a combination of molecular dynamics simulations and quantum mechanical calculations. Molecular dynamics simulations were used to obtain the most populated conformations of the (1R,3S:4S,8S)-p-menthane-3,9-diol as well as the distribution of the solvent molecules around it. Quantum mechanical calculations of NMR chemical shifts were performed on the most relevant conformations employing the GIAO-DFT formalism. A special emphasis was put in evaluating the effects of the surrounding solvent molecules. For this purpose, supermolecule calculations were performed on complexes constituted by the solute and n chloroform molecules, where n ranges from 3 to 16. An excellent agreement with experimental data has been obtained following this computational strategy.     

Determinants of cyanuric acid and melamine assembly in water

While the recognition of cyanuric acid (CA) by melamine (M) and their derivatives has been known to occur in both water and organic solvents for some time, analysis of CA/M assembly in water has not been reported (Ranganathan, A.; Pedireddi, V. R.; Rao, C. N. R. J. Am. Chem. Soc.1999, 121, 1752-1753; Mathias, J. P.; Simanek, E. E.; Seto, C. T.; Whitesides, G. M. Macromol. Symp.1994, 77, 157-166; Zerkowski, J. A.; MacDonald, J. C.; Seto, C. T.; Wierda, D. A.; Whitesides, G. M. J. Am. Chem. Soc.1994, 116, 2382-2391; Mathias, J. P.; Seto, C. T.; Whitesides, G. M. Polym. Prepr.1993, 34, 92-93; Seto, C. T.; Whitesides, G. M. J. Am. Chem. Soc.1993, 115, 905-916; Zerkowski, J. A.; Seto, C. T.; Whitesides, G. M. J. Am. Chem. Soc.1992, 114, 5473-5475; Seto, C. T.; Whitesides, G. M. J. Am. Chem. Soc.1990, 112, 6409-6411; Wang, Y.; Wei, B.; Wang, Q. J. Chem. Cryst.1990, 20, 79-84; ten Cate, M. G. J.; Huskens, J.; Crego-Calama, M.; Reinhoudt, D. N. Chem.-Eur. J.2004, 10, 3632-3639). We have examined assembly of CA/M, as well as assembly of soluble trivalent CA and M derivatives (TCA/TM), in aqueous solvent, using a combination of solution phase NMR, isothermal titration and differential scanning calorimetry (ITC/DSC), cryo-transmission electron microscopy (cryo-TEM), and synthetic chemistry. While the parent heterocycles coprecipitate in water, the trivalent system displays more controlled and cooperative assembly that occurs at lower concentrations than the parent and yields a stable nanoparticle suspension. The assembly of both parent and trivalent systems is rigorously 1:1 and proceeds as an exothermic, proton-transfer coupled process in neutral pH water. Though CA and M are considered canonical hydrogen-bonding motifs in organic solvents, we find that their assembly in water is driven in large part by enthalpically favorable surface-area burial, similar to what is observed with nucleic acid recognition. There are currently few synthetic systems capable of robust molecular recognition in water that do not rely on native recognition motifs, possibly due to an incomplete understanding of recognition processes in water. This study establishes a detailed conceptual framework for considering CA/M heterocycle recognition in water which enables the future design of molecular recognition systems that function in water.     

On the Use of Accelerated Molecular Dynamics to Enhance Configurational Sampling in Ab Initio Simulations

We have implemented the accelerated molecular dynamics approach (Hamelberg, D.; Mongan, J.; McCammon, J. A. J. Chem. Phys. 2004, 120 (24), 11919) in the framework of ab initio MD (AIMD). Using three simple examples, we demonstrate that accelerated AIMD (A-AIMD) can be used to accelerate solvent relaxation in AIMD simulations and facilitate the detection of reaction coordinates: (i) We show, for one cyclohexane molecule in the gas phase, that the method can be used to accelerate the rate of the chair-to-chair interconversion by a factor of ～1 × 10(5), while allowing for the reconstruction of the correct canonical distribution of low-energy states; (ii) We then show, for a water box of 64 H(2)O molecules, that A-AIMD can also be used in the condensed phase to accelerate the sampling of water conformations, without affecting the structural properties of the solvent; and (iii) The method is then used to compute the potential of mean force (PMF) for the dissociation of Na-Cl in water, accelerating the convergence by a factor of ～3-4 compared to conventional AIMD simulations.(2) These results suggest that A-AIMD is a useful addition to existing methods for enhanced conformational and phase-space sampling in solution. While the method does not make the use of collective variables superfluous, it also does not require the user to define a set of collective variables that can capture all the low-energy minima on the potential energy surface. This property may prove very useful when dealing with highly complex multidimensional systems that require a quantum mechanical treatment.     

Polarizable and flexible model for ethanol

A polarizable, flexible model for ethanol is obtained based on an extensive series of B3LYP/6-311++G(d,p) calculations and molecular dynamics simulations. The ethanol model includes electric-field dependence in both the atomic charges and the intramolecular degrees of freedom. Field-dependent intramolecular potentials have been attempted only once previously, for OH and HH stretches in water [P. Cicu et al., J. Chem. Phys. 112, 8267 (2000)]. The torsional potential involving the hydrogen-bonding hydrogen in ethanol is found to be particularly field sensitive. The methodology for developing field-dependent potentials can be readily generalized to other molecules and is discussed in detail. Molecular dynamics simulations of bulk ethanol are performed and the results are assessed based on comparisons with the self-diffusion coefficient [N. Karger et al., J. Chem. Phys. 93, 3437 (1990)], dielectric constant [J. T. Kindt and C. A. Schmuttenmaer, J. Phys. Chem. 100, 10373 (1996)], enthalpy of vaporization [R. C. Wilhoit and B. J. Zwolinski, J. Phys. Chem. Ref. Data, Suppl. 2, 2 (1973)], and experimental interatomic distributions [C. J. Benmore and Y. L. Loh, J. Chem. Phys. 112, 5877 (2000)]. The simultaneous variation of the atomic charges and the intramolecular potentials requires modified equations of motion and a multiple time step algorithm has been implemented to solve these equations. The article concludes with a discussion of the bulk structure and properties with an emphasis on the hydrogen bonding network.     

Hydroxyl radical and hydroxide ion in liquid water: a comparative electron density functional theory study

Ab initio density functional theory molecular dynamics simulations of the solvated states of the hydroxyl radical and hydroxide ion are performed using the Becke-Lee-Yang-Parr (BLYP) exchange-correlation functional (Becke, A. D. Phys. Rev. A 1988, 38, 3098. Lee, C.; Yang, W.; Parr, R. G. Phys. Rev. B 1988, 37, 785). The structures of the solvation shells of the two species are examined. It is found that the OH radical forms a relatively well-defined solvation complex with four neighboring water molecules. Three of these molecules are hydrogen bonded to the OH, while the fourth is hemibonded via a three-electron two-centered bond between the oxygen atoms of the OH and water. The activity and the diffusion mechanism of the OH radical in water is discussed in comparison with the OH- ion. Although the results are partially influenced by the tendency of the BLYP density functional to overestimate hemibonded structure, the present simulations suggest that the widely accepted picture of rapid diffusion of OH radical in water through hydrogen exchange reaction may need to be reconsidered.     

Small-angle neutron scattering studies of charged carboxyl-terminated dendrimers in solutions

Small-angle neutron scattering was used to characterize the solution behavior of charged carboxylic acid terminated "cascade" dendrimers (Z-Cascade/methane [4]/3-oxo-6-oxa-2-azaheptylidyne/3-oxo-2-azaheptylidyne/propanoic acids) of third (G3) and fifth (G5) generations as a function of dendrimer concentration, pH, and ionic strength. An increase in dendrimer concentration leads to a single broad peak in the scattering profile arising from interdendrimer interaction. The dissociation of terminal carboxylate groups also gives rise to an interdendrimer interaction peak, which could be suppressed by the addition of excess salt. The results of contrast matching measurements indicate the accumulation of an excess concentration of tetramethylammonium counterions around the surface of these highly charged particles, and the thickness of these counterions lies somewhere between 4 and 6 A. This conclusion is consistent with our previous potentiometric titration (Zhang, H.; et al. J. Phys. Chem. B 1997, 101, 3494) and capillary electrophoresis (Huang, Q. R.; et al. J. Phys. Chem. B 2000, 104, 898) data.     

From homogeneous dispersion to micelles-a molecular dynamics simulation on the compromise of the hydrophilic and hydrophobic effects of sodium dodecyl sulfate in aqueous solution

The structural and functional diversity of surfactant systems has attracted simulation works in atomistic, coarse grain, and mesoscopic models (Bandyopadhyay, S.; et al. Langmuir 2000, 16, 942; Senapati, S.; et al. J. Phys. Chem. B 2003, 107, 12906; Maiti, P. K.; et al. Langmuir 2002, 18, 1908; Srinivas, G.; et al. J. Phys. Chem. B 2004, 108, 8153; Groot, R. D.; et al. J. Chem. Phys. 1999, 110, 9739; Rekvig, L.; et al. Langmuir 2003, 19, 8195). However, atomistic models have suffered from their tremendous computational cost and are, so far, not able to simulate the structural behaviors in sufficient spatio-temporal scales (Shelley, J. C.; Shelley, M. Y. Curr. Opin. Colloid Interface Sci. 2000, 5, 101). The other two approaches are not microscopic enough to describe the configurations of the surfactants that determine their behaviors (Shelley and Shelley). In this study, we propose to simplify atomistic models based on the observation that the compromise of the hydrophilic and hydrophobic effects (Li, J.; Kwauk, M. Chem. Eng. Sci. 2003, 58, 521-535) and molecular structures of surfactants are the dominant factors shaping their structures in the systems. With this simplification, we are able to simulate with moderate computing cost the whole process of micelle formation from an initially uniform dispersion of sodium dodecyl sulfate (SDS) in aqueous solution. The resulting micelle structures are different from those predicted by atomistic simulations that started with a predefined micelle configuration at the same surfactant concentrations. However, if we use their initial micelle configuration, micelle structures the same as theirs are obtained. Analyses show that our results are more realistic and that the results of the atomistic simulations suffer from artificial initial conditions. Therefore, our model may serve as a reasonable simplification of atomistic models in terms of the general structure of micelles.     

How does trimethylamine N-oxide counteract the denaturing activity of urea?

Trimethylamine N-oxide, TMAO, stabilizes globular proteins and is able to counteract the denaturing activity of urea. The mechanism of this counteraction has remained elusive up to now. A rationalization is proposed grounded on the same theoretical model used to clarify the origin of cold denaturation, and the denaturing activity of GdmCl versus the stabilizing one of Gdm(2)SO(4) [G. Graziano, Phys. Chem. Chem. Phys., 2010, 12, 14245-14252; G. Graziano, Phys. Chem. Chem. Phys., 2011, 13, 12008-12014]. The fundamental quantities are: (a) the difference in the solvent-excluded volume on passing from the N-state to the D-state, calculated in water and in aqueous osmolyte solution; (b) the difference in energetic attractions of the N-state and the D-state with the surrounding solvent molecules, calculated in water and in aqueous osmolyte solution. In aqueous 8 M urea + 4 M TMAO solution, the first quantity is so large and positive to counteract the second one that is large and negative due to preferential binding of urea molecules to the protein surface. This happens because aqueous 8 M urea + 4 M TMAO solution has a volume packing density markedly larger than that of water, rendering the cavity creation process much more costly. The volume packing density increase reflects the strength of the attractions of water molecules with both urea and TMAO molecules. This mechanism readily explains why TMAO counteraction is operative even though urea molecules are preferentially located on the protein surface.     

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.