Role of Terminal Groups of cis-1,4-Polyisoprene Chains in the Formation of Physical Junction Points in Natural Rubber.

The terminal structures of cis-1,4-polyisoprene (PI) chains play a vital role in the excellent comprehensive performance of Hevea natural rubber (NR) with properties such as high toughness, tear-resistance, and wet skid resistance. The cis-1,4-polyisoprene chain constituting NR exhibits a distinct composition of terminal groups comprising two distinct types, namely, the ω and α terminal groups. The structures of the ω terminal [dimethyl allyl (DMA)-(trans-1,4-isoprene)2] and six kinds of α end groups of the polymer chain of NR have been explored by utilizing a newly developed 2D NMR method. In the present work, we examine different kinds of PI melt systems, and we choose various combinations of terminal groups: Hydrogen, one DMA unit with two trans isoprene units as ω end groups and ester-terminated isopentene (α1), hydroxy-terminated isopentene (α2), ester-terminated isobutane (α3), hydroxy-terminated isobutane (α4), ester-terminated 1,4-cis-isoprene (α5), and hydroxy-terminated 1,4-cis-isoprene (α6), i.e., HPIH (PI0)-pure PI (Hydrogen terminal), ωPIα1 (PII), ωPIα2 (PIII), ωPIα3 (PIIII), ωPIα4 (PIIV), ωPIα5 (PIV), and ωPIα6 (PIVI). We evaluated dynamic and static properties of PI chains such as the end-to-end vector autocorrelation function (C(t)), its average relaxation time (τ), end-to-end distance (Ree), and radius of gyration (Rg). We also estimated the diffusion coefficients of polyisoprene chains and pair correlation functions [radial distribution functions (RDFs)], potentials of mean force (PMFs) in between end residues, and survival probability (P(τ)) of end groups around the end group by analyzing the equilibrated trajectories of full-atom MD simulations. As per the examination of C(t), rotational relaxation time τ, and RDFs, we discovered that the existence of a strong hydrogen bond in α2-α2, α4-α4, and α6-α6 residues makes the dynamics of hydroxy-terminated polyisoprene chains in ωPIα2,α4,α6 melt systems slower. From the analyses of RDFs and PMFs (W(r)), the association between [α2]-[α2], [α4]-[α4], and [α6]-[α6] terminals in ωPIα2,α4,α6 melt systems is significantly stronger than in [ISO]-[ISO] [Hydrogen terminated 1,4-cis-isoprene:(ISO)] in HPIH and ω-ω, [α1]-[α1], [α3]-[α3], and [α5]-[α5] in ωPIα1,α3,α5 systems. We quantified the fraction of cluster formation of terminal groups of a given size in the seven PI melt systems by employing the criteria of PMFs. It is revealed that no stable cluster exists in the HPIH, ωPIα1, ωPIα3, and ωPIα5 melt systems. Conversely, in the ωPIα2, ωPIα4, and ωPIα6 systems, we perceived stable clusters of [(α2)p] [(α4)p] and [(α6)p] end groups where p (2 ≤ x ≤ 6). These stable clusters validate the presence of physical junction points in between hydroxy-terminated polyisoprene chains through their α2, α4, and α6 terminals. These physical junction points might be crucial for superior properties of NR such as high toughness, crack growth resistance, and strain-induced crystallization.

Hydrophobic association and solvation of neopentane in urea, TMAO and urea-TMAO solutions.

A detailed knowledge of hydrophobic association and solvation is crucial for understanding the con-formational stability of proteins and polymers in osmolyte solutions. Using molecular dynamics simulations, it is found that the hydrophobic association of neopentane molecules is greater in a mixed urea-TMAO-water solution in comparison to that in 8 M urea solution, 4 M TMAO solution and neat water. The neopentane association in urea solution is greater than that in TMAO solution or neat water. We find the association is even less in TMAO solution than pure water. From free energy calculations, it is revealed that the neopentane sized cavity creation in mixed urea-TMAO-water is most unfavorable and that causes the highest hydrophobic association. The cavity formation in urea solution is either more unfavorable or comparable to that in TMAO solution. Importantly, it is found that the population of neopentane-neopentane contact pair and the free energy contribution for the cavity formation step in TMAO solution are very sensitive towards the choice of TMAO force-fields. A careful construction of TMAO force-fields is important for studying the hydrophobic association. Interestingly it is observed that the total solute-solvent dispersion interaction energy contribution is always the most favorable in mixed urea-TMAO-water. The magnitude of this interaction energy is greater in urea solution relative to TMAO solution for two different force-fields of TMAO, whereas the lowest value is obtained in pure water. It is revealed that the extent of the overall hydrophobic association in osmolyte solutions is mainly governed by the cavity creation step and it nullifies the contribution coming from the solute-solvent interaction contribution.

Free energy of hydrophilic and hydrophobic pores in lipid bilayers by free energy perturbation of a restraint.

The free energy of pore formation in lipid bilayers has been previously calculated using a variety of reaction coordinates. Here, we use free energy perturbation of a cylindrical lipid exclusion restraint to compute the free energy profile as a function of pore radius in dimyristoylphosphatidylcholine (DMPC) and dioleoylphosphatidylcholine (DOPC) bilayers. Additionally restraining the headgroups to lie on the membrane surface allows us to also calculate the free energy profile of hydrophobic pores, i.e., cylindrical pores lined by acyl chains. For certain pore radii, the free energy of wetting of hydrophobic pores is calculated using the density bias method. It is found that wetting of hydrophobic pores becomes thermodynamically favorable at 5.0 Å for DMPC and 6.5 Å for DOPC, although significant barriers prevent spontaneous wetting of the latter on a nanosecond time scale. The free energy of transformation of hydrophilic pores to hydrophobic ones is also calculated using free energy perturbation of headgroup restraints along the bilayer normal. This quantity, along with wetting and pore growth free energies, provides complete free energy profiles as a function of radius. Pore line tension values for the hydrophilic pores obtained from the slope of the free energy profiles are 37.6 pN for DMPC and 53.7 pN for DOPC. The free energy profiles for the hydrophobic pores are analyzed in terms of elementary interfacial tensions. It is found that a positive three-phase line tension is required to explain the results. The estimated value for this three-phase line tension (51.2 pN) lies within the expected range.

Ionic Pairing and Selective Solvation of Butylmethylimidazolium Chloride Ion Pairs in DMSO-Water Mixtures: A Comprehensive Examination via Molecular Dynamics Simulations and Potentials of Mean Force Analysis.

Ionic liquids (ILs) with dimethyl sulfoxide (DMSO) and water act as a promising solvent medium for the dissolution of cellulose in an efficient manner. To develop a proper solvent system, it is really important to understand the thermodynamics of the molecular solutions consisting of ILs, DMSO, and water. The ion-pairing propensity of the ILs in the presence of DMSO and water plays a crucial role in governing the property of the solvent mixtures. Employing all-atom molecular dynamics simulations, we estimate the potentials of mean force between BMIM+ and Cl- ions in DMSO-water mixtures. Analysis reveals a significant increase in the thermodynamic stability of both contact ion pair (CIP) and solvent-assisted ion pair (SAIP) states with a rising DMSO mole fraction. Thermodynamic assessments highlight the entropic stabilization of CIP states and SAIP states in pure water, in DMSO-water mixtures, and in pure DMSO. The structural analysis reveals that in comparison to the DMSO local density, the local water density is relatively very high around ion pairs, more specifically in the solvation shell of a chloride ion. Preferential binding coefficients also consistently indicate exclusion of DMSO from the ion pair in DMSO-water mixtures. To enhance our understanding regarding the solvent molecules kinetics around the ion pairs, the survival probabilities of DMSO and water are computed. The calculations reveal that the water molecules prefer a prolonged stay in the solvation shell of Cl- ions.

Solvation structures and dynamics of the magnesium chloride (Mg(2+)-Cl(-)) ion pair in water-ethanol mixtures.

We have performed constrained molecular dynamics simulations of magnesium chloride in water-ethanol mixtures. From the potentials of mean force (PMFs) of the Mg(2+)-Cl(-) ion pair, we notice that, as the mole fraction of ethanol increases, the depths of the minima of the contact ion pair (CIP) and solvent assisted ion pair (SAIP) increase, but the depth of the CIP minimum increases more in comparison to the SAIP minimum. This shows that ion pairing becomes more favorable with an increase in the mole fraction of ethanol. Significant differences in the PMFs between the Mg(2+) and the Cl(-) ion (depending upon whether the second Cl(-) ion is present in the first coordination shell of the Mg(2+) ion or not) seem to have been reported for the first time in this work. The local mole fraction of water molecules in the first solvation shell of ions is generally greater than in the bulk. The diffusional behavior of solvent molecules in solvation shells of the ion-pair indicates that the ions as well as the first solvation shells of the ions diffuse at much slower rates. Also, the diffusion constant of bulk water in the mixtures is greatly reduced compared to the pure solvent value.

SPICA Force Field for Proteins and Peptides.

A coarse-grained (CG) model for peptides and proteins was developed as an extension of the Surface Property fItting Coarse grAined (SPICA) force field (FF). The model was designed to examine membrane proteins that are fully compatible with the lipid membranes of the SPICA FF. A preliminary version of this protein model was created using thermodynamic properties, including the surface tension and density in the SPICA (formerly called SDK) FF. In this study, we improved the CG protein model to facilitate molecular dynamics (MD) simulations with a reproduction of multiple properties from both experiments and all-atom (AA) simulations. An elastic network model was adopted to maintain the secondary structure within a single chain. The side-chain analogues reproduced the transfer free energy profiles across the lipid membrane and demonstrated reasonable association free energy (potential of mean force) in water compared to those from AA MD. A series of peptides/proteins adsorbed onto or penetrated into the membrane simulated by the CG MD correctly predicted the penetration depths and tilt angles of peripheral and transmembrane peptides/proteins as comparable to those in the orientations of proteins in membranes (OPM) database. In addition, the dimerization free energies of several transmembrane helices within a lipid bilayer were comparable to those from experimental estimation. Application studies on a series of membrane protein assemblies, scramblases, and poliovirus capsids demonstrated the good performance of the SPICA FF.

Amphotericin B assembles into seven-molecule ion channels: An NMR and molecular dynamics study.

Amphotericin B, an antifungal drug with a long history of use, forms fungicidal ion-permeable channels across cell membranes. Using solid-state nuclear magnetic resonance spectroscopy and molecular dynamics simulations, we experimentally elucidated the three-dimensional structure of the molecular assemblies formed by this drug in membranes in the presence of the fungal sterol ergosterol. A stable assembly consisting of seven drug molecules was observed to form an ion conductive channel. The structure is somewhat similar to the upper half of the barrel-stave model proposed in the 1970s but substantially different in the number of molecules and in their arrangement. The present structure explains many previous findings, including structure-activity relationships of the drug, which will be useful for improving drug efficacy and reducing adverse effects.

Uterine and ovarian parameters in healthy North Indian girls from 5 to 16 years by ultrasonography.

INTRODUCTION: Knowledge of uterine and ovarian growth patterns during early age and puberty helps in investigating disorders of pubertal development i.e. precocious puberty, premature thelarche, or pubarche. There is a paucity of data for uterine and ovarian parameters. Aim of the study: The aim of this study is to present normative data for Uterine length, Mean ovarian volume (MOV), and fundo cervical ratio (FCR) from 5 to 16 years in healthy girls from north India and to correlate these parameters with age, weight, height, and pubertal Tanner staging. MATERIAL AND METHODS: A cross-sectional observational study was performed on 130 healthy girls age 5 to 16 years. Age, anthropometric parameters were measured and the pubertal stage was categorized using Tanner staging. All subjects underwent pelvic ultrasonography for the measurement of uterine and ovarian parameters. RESULTS: Normative data of uterine length, MOV, and FCR were presented as mean, SD, median, and 95% confidence interval as per age and Tanner stage. A progressive increase in uterine length, MOV & FCR was observed with increasing age, weight, height, and Tanner stage (p < 0.001). A sudden significant increment in uterine length and MOV was observed between the age of 11-12 and 12-13 years (p < 0.001). Uterine length of < 4 cm, MOV < 2 cm3 and FCR < 1 were specific to identify pre-pubertal girls. CONCLUSIONS: Normative data of uterine and ovarian parameters generated in our study by ultrasonography would be useful for screening girls with abnormalities of pubertal development.

Progressive Hydrophobicity of Fluorobenzenes.

The potentials of mean force for the dimers of fluorobenzenes sample both π-stacked and T-shaped structures for partially fluorinated benzenes, namely, 1,4-difluorobenzene, 1,3,5-trifluorobenzene, and 1,2,4,5-tetrafluorobenzene, and sample only the T-shaped structures for benzene and hexafluorobenzene. While the free energy for the dimerization in water is very weakly dependent on the number of fluorine atoms, the formation of π-stacked structures is entropy-driven and the T-shaped structures appear due to an enthalpic minimum. Interestingly, the solvation behavior suggests that the accumulation of water around the contact and solvent-separated pairs decreases with the increase in the number of fluorine atoms, which signifies progressive hydrophobicity of fluorobenzenes.

Salting-Out of Methane in the Aqueous Solutions of Urea and Glycine-Betaine.

We have studied the hydrophobic association and solvation of methane molecules in aqueous solutions of urea and glycine betaine (GB). We have calculated the potentials of mean force (PMFs) between methane molecules in water, aqueous GB, aqueous urea and aqueous urea-GB mixtures. The PMFs and equilibrium constants indicate that both urea and GB increase the hydrophobic association of methane. Calculation of thermodynamic parameters shows that the association of methane is stabilized by entropy whereas solvation is favored by enthalpy. In the case of the water-urea-GB mixture, both hydrophobic association and solvation are stabilized by entropy. From the investigation of radial distribution functions, running coordination numbers and excess coordination numbers, we infer that both urea and GB are preferentially excluded from methane surface in the mixtures of osmolytes and methane is preferentially solvated by water molecules in all the mixtures. The favorable exclusion of both urea and GB from the methane surface suggests that both urea and GB increase the interaction between methane molecules, i.e., salting-out of methane. We observe that addition of both urea and GB to water enhances local water structure. The calculated values of diffusion constants of water also suggest enhanced water-water interactions in the presence of urea and GB. The calculated free energies of methane in these mixtures show that methane is less soluble in the mixtures of urea and GB than in water. The data on solvation free energies support the observations obtained from the PMFs of methane molecules.