Abstract  The objective of this study was to investigate the percutaneous absorption of metronidazole (MTZ) in the topical formulations containing a combination of 1,4-cyclohexanediol and 1,2-hexanediol. Six formulations were studied in an in vitro hairless mouse skin model using Franz Diffusion Cell. MTZ was applied at infinite doses (50mg and 100mg of the formulations, which correspond to 375 and 750 μg of MTZ, respectively). Based on the flux values and retardation ratio (RR), a synergistic retardation effect on percutaneous absorption of MTZ was observed for the formulations containing a combination of 1,4-cyclohexanediol and 1,2-hexanediol (RRs are 0.40 for 375 μg dose and 0.69 for 750 μg dose, respectively). Interestingly, retention of MTZ in epidermis and dermis layer showed no significant differences (p>0.05) between the formulations containing the retardant combination and control formulations. In other words, the retardant combination in the formulation decreases MTZ fluxes while maintaining similar level of retention in epidermis and dermis layer when compared to the control formulations. These observations provide insight in formulating superior topical formulations with minimized potential systematic toxicity while maintaining therapeutic efficiency. A mechanistic explanation of the observed synergistic effect is proposed.

Abstract  Several studies have reported that 1,2-alkanediols show increasing anti-microbial activity as their alkane chain length increases. However, there are no reports on the influence of alkane chain length on the skin irritation potential of 1,2-alkanediols. To investigate the influence of alkane chain length on the skin irritation potential of 1,2-alkanediols. The objective and subjective (sensory) skin irritation potentials of five 1,2-alkanediols - 1,2-butanediol, 1,2-pentanediol, 1,2-hexanediol, 1,2-octanediol and 1,2-decanediol - were evaluated. We also estimated percutaneous absorption by measuring in vitro skin penetration using a Franz diffusion cell system. Like anti-microbial activity, sensory irritation potential increased as alkane chain length increased, most likely due to increasing membrane interference and/or intrinsic toxicity of 1,2-alkanediols. 1,2-Hexanediol showed the lowest objective skin irritation potential, which increased when the alkane chain length decreased or increased. Furthermore, percutaneous absorption negatively correlated with the alkane chain length of 1,2-alkanediols. These results show that a lower skin absorption potential is not indicative of a low skin irritation potential. Our results suggest that the factors and processes involved in skin irritation potential are complex and that skin irritation potential is influenced by intrinsic toxicity and the potential for penetration or integration in the lipid bilayer.

Abstract  Optically active alcohol is an important building block as a versatile chiral synthon for the asymmetric synthesis of pharmaceuticals and agrochemicals. We purified and characterized glycerol dehydrogenase from Hansenula ofunaensis and prepared optically active 1,2-octanediol using a recombinant Escherichia coli harboring the glycerol dehydrogenase gene. The deduced amino acid sequence was investigated for identities with those of other alcohol dehydrogenases in the NCBI databank. The identification of the unknown product of a resting-cell reaction was performed by GC-MS. In the deduced amino acid sequence composed of 376 residues, the NAD(H) binding pattern and cysteine residues that correspond to the cysteine ligands at the zinc atom were conserved as they are in alcohol dehydrogenases from other origins. Glycerol dehydrogenase from Hansenula polymorpha DL-1 (Pichia angusta, DDBJ/EMBL/GenBank accession no. BAD32688) had the highest identity to our enzyme, showing 73% identity. Our glycerol dehydrogenase catalyzed the NAD(+)-dependent oxidation of long-chain secondary alcohols such as 1,2-pentanediol, 1,2-hexanediol, 1,2-heptanediol, and 1,2-octanediol. Activities toward 2,4-pentanediol and 2,5-hexanediol were hardly detected. From these results, it was confirmed that our enzyme requires two hydroxyl groups on adjacent carbon atoms for oxidation. 2,3-Pentanedione, 2,3-hexanedione, and 3,4-hexanedione were significantly reduced. The transformants oxidized only (R)-1,2-octanediol in 50 mM racemate (R:S=52:48), and produced (S)-1,2-octanediol (24 mM, <99.9% e.e.) after 24 h of incubation. The reaction product was suggested to be 1-hydroxy-2-octanone by GC-MS, which showed secondary hydroxyl groups oxidized. Glycerol dehydrogenase from H. ofunaensis could be useful for the production of long-chain optically active secondary alcohols.

Abstract  Strontium phenylphosphonate intercalates with 1,2-diols (from 1,2-ethanediol to 1,2-hexanediol) were synthesized and characterized by X-ray diffraction, thermogravimetry, chemical analysis, and molecular simulation methods. Prepared samples exhibit a very good stability at ambient conditions. Structural arrangement calculated by simulation methods suggested formation of cavities surrounded by six benzene rings. Each cavity contained one molecule of diol and one molecule of water for the 1,2-ethanediol to 1,2-butanediol intercalates. In the case of 1,2-pentanediol two types of cavities alternated: one with diol molecules and another one with two water molecules. In the 1,2-hexanediol intercalate the benzene rings created two types of cavities containing one or two diol molecules, respectively, and this conformational variability led to a more disordered arrangement with respect to the models with shorter alkyl chains. Coordination of the oxygen atoms of the diols to the strontium atoms of the host follows the same pattern for all 1,2-diol intercalates except the 1,2-hexanediol intercalate, where these oxygen atoms can be mutually exchanged at their positions. The calculated basal spacings and structural models are in good agreement with experimental basal spacings obtained from X-ray powder diffraction and with other experimental results.

Abstract  Diols with short aliphatic chains were known to exhibit antimicrobial activities, which were found to depend on the chain length and the position of the hydroxyl groups. We carried out the conformational preferences of 1,n-hexanediols (n = 2-6) and (S)-3-alkoxypropane-1,2-diols in the gas phase and in water using density functional methods and explored the factors important to exhibit antimicrobial activities. In the case of 1,2-, 1,3-, and 1,4-hexanediols, intramolecular H-bonds played a role in stabilizing their preferred conformers in the gas phase, whereas they were remarkably depopulated in water. For 1,5-, and 1,6-hexanediols, no H-bonded conformers were favored both in the gas phase and in water. The C-H center dot center dot center dot O interactions appeared to be of consequence in determining the preferred structures of 1,n-hexanediols (n = 3-6) in water. The stabilization of the preferred conformers of (S)-3-alkoxyprop ane-1,2-diols could be ascribed to the bifurcated H-bonds both in the gas phase and in water. However, their populations were decreased and the -CH2-O-(CH2)(m)-CH3 chain became more extended in water. In the optimized structures of dimers and trimers of 1,2-hexanediol and (S)-3-(hexyloxy)propane-1,2-diol in water, the head OH groups are oriented to each other to form intermolecular H-bonds and the aliphatic tails are stretched out away from the head groups, which are likely to form micelle-like structures in water. When two hydroxyl groups become closer and the aliphatic chain becomes longer, the amphipathicity of alkanediol is increased and thus, it is likely to penetrate more easily into membrane bilayers of the microbial cell and may disrupt the membrane structure. (C) 2015 Elsevier B.V. All rights reserved.

Abstract  The present study was aimed at the encapsulation of ketoconazole (KCZ) in the novel modified nanovesicles for dermal targeting delivery. To this purpose, innovative modified vesicles were prepared with soy phospholipid and aqueous solutions containing different concentrations of two targeting modifiers, 1,2-hexanediol and 1,4-cyclohexanediol. Conventional liposomes, with soy phospholipid and cholesterol, were used as control. The prepared formulations were characterized in terms of entrapment efficiency, size distribution, morphology, and stability. Dermal KCZ targeting delivery from modified vesicles was investigated in vitro and in vivo through newborn pig and rat skin, respectively. All vesicles showed a mean size ranging from 58 to 147 nm with fairly narrow size distribution and drug entrapment efficiency between 20 and 75 %. Results of in vitro and in vivo studies indicated that modified vesicles provided an improved KCZ targeting delivery into skin layers. Images of the confocal laser scanning microscopy analyses supported the conclusion that modified vesicles could enhance the drug deposition into the skin strata and reduce the drug permeation into the blood, due to a synergic effect of phospholipid and modifiers. Finally, histological evaluation showed that KCZ-loaded modified vesicles caused no irritation to the skin. The results obtained encouraged the use of the KCZ-loaded modified vesicles as the formulation for the potential topical treatment of fungal infections.

Abstract  This article describes the formation of microemulsions by utilising fatty acid methyl esters (FAME) and a surfactant or mixed surfactant system derived from palm oil-based oleochemicals. The effects of 1,2 hexanediol as a conventional non-toxic co-surfactant were investigated by observing the ternary phase behaviour of palm oil-based microemulsions for three types of surfactant systems, i.e., fatty alcohol ethoxylates 7EO (FAE 7); mixed surfactants FAE 7 and fatty alcohol ethoxylates 2EO (FAE 2) in a 75:25 ratio; and mixed surfactants FAE 7, FAE 2 and methyl ester sulphonate (MES) in a 60:20:20 ratio. The microemulsion (mu E) solutions formed were characterised by conductivity, viscosity and droplet-size measurements. The cleaning performance of selected palm oil-based microemulsions as all-purpose spray liquid cleaners for hard surfaces is also reported.

Abstract  Experimental data are presented for liquid-liquid equilibria of mixtures of the room-temperature ionic liquid 1-ethyl-3-methyl-imidazolium bis(trifluoromethylsulfonyl)imide ([C2MIM][NTf2]) with the three alcohols propan-1-ol, butan-1-ol, and pentan-1-ol and for the 1-butyl-3-methyl-imidazolium bis(trifluoromethylsulfonyl)imide ([C4MIM] [NTf2]) with cyclohexanol and 1,2-hexanediol in the temperature range of 275 K to 345 K at ambient pressure. The synthetic method has been used. Cloud points at a given composition were observed by varying the temperature and using light scattering to detect the phase splitting. In addition, the influence of small amounts of water on the demixing temperatures of binary mixtures of [C2MIM][NTf2] and propan-1-ol, butan-1-ol, and pentan-1-ol was investigated.

Abstract  We present small-angle neutron scattered intensity measurements in heavy water binary solutions of some short-chain glycols (diols and triols) at room temperature. The spectra were analyzed in terms of a model which takes into account the simultaneous presence of spherical aggregates and concentration fluctuations. We found that hydrated micelle-like aggregates are present in some bi- and trivalent alcohols (e.g., 1,2-hexanediol, 1,2,3-octanetriol) and are absent in others (e.g., 2,5-hexanediol, 1,2,3-hexanetriol). Results are discussed in terms of location of the polar hydroxyl groups in the short hydrocarbon chain. The size and aggregation numbers of the found aggregates are compared with those of other short-chain nonionic surfactants.

Abstract  N,N-Dimethyldodecylamine N-oxide (DDAO), PVP and PVA capped supported AuPd bimetallic nanoparticles (NPs) were prepared, and their catalytic activities were evaluated for the oxidation of 1,6-hexanediol (HDO) to 6-hydroxycaproic acid (HCA) using H2O2 in basic aqueous solution. Among three catalysts, DDAO capped AuPd bimetallic NPs catalysts exhibited superior selectivity for HCA formation than PVP and PVA capped catalysts. To explain the difference in the catalytic behavior, the catalysts were characterized thoroughly. XRD, TEM and STEM-HAADF-EDS studies were employed to identify the structure and morphology of capped AuPd-NPs, respectively. The chemical and electronic states were elucidated using XPS and XAS methods. The characterization data revealed that the capping agent significantly influences the electron density on metals and extent of alloying between Au and Pd metals. It was revealed that DDAO-capped catalyst induces appropriate negatively charged Au species with a few numbers of Au-Pd interfaces for the highly selective formation of HCA via HDO oxidation in basic aqueous media. Furthermore, other aliphatic diols, 1,7-heptanediol, 1,8-octanediol and 1,2-hexanediol, were also selectively oxidized on AuPd-DDAO catalysts toward the corresponding omega-hydroxycarboxylic acids in high yields. (C) 2015 Elsevier B.V. All rights reserved.

Abstract  Hydrogenolysis of alcohols was carried out using n-heptane solvent and Ir-ReOx/SiO2 catalyst, which has been known to be active in water solvent. Hydrogenolysis of trans-1,2-cyclohexanediol proceeded more smoothly in n-heptane than in water. The maximum yield of cyclohexanol was 74%, and at longer reaction time cyclohexane was selectively formed (>80% yield). Stronger adsorption of substrate on catalyst surface in n-heptane than in water is one of factors in obtaining the good yields. Alkane solvent was also advantageous to water solvent in hydrogenolysis of mono-alcohols. The reaction route via acid-catalyzed dehydration and subsequent hydrogenation is enhanced in alkane solvent. On the other hand, the "direct" hydrogenolysis driven by the hydride-like species is suppressed in alkane solvent, leading lower activity in n-heptane for hydrogenolysis of tetrahydrofurfuryl alcohol or 1,2-hexanediol, which smoothly react over Ir-ReOx/SiO2 catalyst in water. (C) 2013 Elsevier B.V. All rights reserved.

Abstract  The extraction of 1,2-hexanediol from aqueous solution by dihydroxyphenylborane was studied in the absence and presence of tri-n-octylmethylammonium chloride (TOMAC) to establish a process of microbial kinetic resolution of epoxides. Dihydroxyphenylborane alone could extract 1,2-hexanediol except at high pH. Addition of TOMAC to the extractant solution significantly improved the distribution of 1,2-hexanediol to the organic solution at high pH. The extraction mechanisms of 1,2-hexanediol in these systems were elucidated and extraction equilibrium constants were determined.

Abstract  The dielectric spectra of binary liquid mixtures of the following alcohols with N,N-dimethylformamide (DMFA) have been measured between 5 MHz and 72 GHz at 20 degrees C:1-Hexanol, 1,2-hexanediol and 1,4-butanediol. The analysis of the spectra, which is particularly aimed at information on hetero-association, gives evidence for the formation of mixed aggregations, indicated by a minimum in the 'free' DMFA relaxation contribution at a mixture ratio of about 1:1 for hexanol/DMFA and about 1:2 in case of the dihydric alcohol/DMFA systems.

Abstract  Aqueous solutions of 1,2-pentanediol, 1,5-pentanediol, 1,2-hexanediol and 1,6-hexanediol have been studied by small-angle neutron scattering over a wide range of concentrations and temperatures. The structure of the solutions on the mesoscopic length scale, corresponding to the intermolecular distances, was analysed with the help of the Kirkwood-Buff formalism. 1,2-Hexanediol solutions exhibited a strong attractive diol-diol interaction, a weak diol-diol attraction was found for 1,6-hexanediol and 1,2-pentanediol, and an extremely weak diol-diol attraction was found in 1,5-pentanediol solutions. The general tendencies are the following: aggregation is stronger as the length of the hydrophobic hydrocarbon chain increases and the 1,2-diols exhibit much stronger attraction then the 1,omega-diols. The temperature dependence of the aggregation is weak for the 1,2-diols but strong for the 1,omega-diols, indicating in the latter case the hydrophobic character of the interaction.

Abstract  The purpose of the present study was to determinate the significance of ion pairing on the topical permeation of retinoic acid (R.A) using microemulsions as delivery vehicles. Phenylalanine methyl ester, phenylalanine ethylester, histidine methyl ester, tryptophan methyl ester and valine methyl ester were used as counter ions. Results of diffusion studies through polydimethylsiloxane membrane (PDMS) indicate that retinoic acid permeation from ethanol-pH 6.4 buffer mixture significantly increased in the presence of counter ions. A linear relationship was found between apparent partition coefficients and permeation coefficients. The highest values were with valine methyl ester and phenylalanine ethyl ester. In order to develop alternative formulations for topical administration of R.A, microemulsions were evaluated as delivery vehicles. Oil-in-water (O/W) and water-in-oil (W/O) microemulsion formulations were prepared using water, isopropyl myristate, lecithin, caprylyl-capryl glucoside and ethanol or 1,2 hexanediol. Experiments with PDMS membranes showed decreasing permeabilities of R.A from microemulsions in the presence of counter ions. This was related to the increased lipophilicity and different vehicle membrane affinity of the ion pairs The ability of the systems to deliver R.A through the skin was evaluated in vitro using pig-skin. R.A permeabilities were much lower with microemulsions than with solution, while a large increase in R.A skin deposition was observed only from O/W microemulsions in the presence of counter ions. The depth of skin accumulation was below 100 mum after 24 h application. The results suggest that O/W microemulsions containing a counter ion can be used to optimise drug targeting without a concomitant increase in systemic absorption. (C) 2002 Elsevier Science B.V. All rights reserved.

Abstract  Excess molar volumes V-m(E) and partial molar volumes (V) over bar (2) have been determined from density measurements for dilute aqueous solution of 1.2-hexanediol, 1.5-hexanediol, 1,6-hexanediol, and 2,5-hexanediol at (283.15, 288.15, 293.15, 298.15, 303.15, and 308.15) K as a function of composition. The infinite dilution partial molar volumes (V) over bar (infinity)(2) of alcohols in aqueous solution are evaluated through extrapolation. Interactions of the different solutes with water are discussed in terms of the effect of the position of the hydroxyl groups in the hexanediol molecule. The limiting slope of the partial molar volumes is interpreted in terms of alkanediol hydration. (c) 2007 Elsevier Ltd. All rights reserved.

Abstract  Blends of immiscible polymers are often stabilized by block copolymers which can form non-aqueous micelles and microemulsions in the liquid polymers. The phase diagrams, apparent volumes and apparent heat capacities of model non-aqueous binary and ternary systems were studied in order to investigate the conditions under which such self-assembly systems could form. 1,2-Hexanediol, which can cosolubilize hexane and ethyleneglycol forms inverse micelles in hexane and weak microaggregates in ethyleneglycol. Genapol X-060, a commercial alcoholic surfactant containing on the average an aliphatic chain of 13 carbons and 6 oxyethylenes (C13E6), forms microaggregates in poly(ethyleneglycol) 400. Them self-assembly systems are strengthen in the presence of a third component which has an affinity for the inner phase.

Abstract  Epoxide hydrolase catalysed resolution of aliphatic terminal epoxides has been demonstrated for the hydrolysis of a homologous range of unbranched 1,2-epoxyalkanes by the yeast Rhodotorula glutinis. Both enantioselectivity and reaction rate were strongly influenced by the chain length of the epoxide used. Enantioselectivity showed an optimum in the hydrolysis of 1,2-epoxyhexane (E=84), Resolution of (+/-)-1,2-epoxyhexane resulted in (S)-1,2-epoxyhexane (e.e.>98%, yield=48%) and (R)-1,2-hexanediol (e.e.=83%, yield=47%). (C) 1998 Elsevier Science Ltd. All rights reserved.

Abstract  Continuing our research work on ionic liquids new results for liquid-liquid equilibria (LLE) of binary mixtures of the ionic liquids 1-butyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide ([C4MIM][NTf2]) or 1-hexyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide ([C6MIM][NTf2]) and hexan-1-ol are presented. For the mixture [C4MIM][NTf2]+1,2-hexanediol the interfacial tension gamma between the two liquid phases being in equilibrium has been measured as a function of temperature using a pendant-drop tensiometer.

Additionally, for systems [C4MIM][NTf2]+alcohol the influence of impurities like 1-methylimidazole and water on the demixing temperature was investigated. (C) 2006 Elsevier B.V. All rights reserved.

Abstract  Microemulsions prepared using 1-decanol, oleic acid or oleyl alcohol as oils, Transcutol and 1,2-hexanediol as surfactant mixture and phosphate buffer pH 6.0 as aqueous phase were studied to verify the effect of the oils on pig-skin permeation and accumulation of acyclovir (ACV). Pseudoternary phase diagrams were constructed in the absence and in the presence of ACV. ACV-containing microemulsions had a restricted area of existence compared to those without the drug. A cationic charge-inducing agent, L-alanine benzyl ester, was added to the formulations to prepare positively-charged microemulsions. Full-thickness pig ear skin was used for ACV permeation experiments using positively-andnegatively-charged microemulsions and a control suspension. The presence of oleyl alcohol or oleic acid increased the flux but not the drug skin accumulation compared to a control suspension, while the use of the cationic charge-inducing agent had no influence on the formulation performance. A two-fold increase in ACV accumulation was found using the microemulsions containing 1-decanol, maintaining intact the structure of the stratum corneum, as demonstrated by the DSC analysis. Microemulsions containing 1-decanol could significantly optimize drug targeting, maintaining the structure of the stratum corneum intact.