Dialkyl Chain Research Articles

Minimal Lipidation Stabilizes Protein-Like Molecular Architecture

Peptide-amphiphiles with collagen-model head groups and dialkyl chain tails have been shown previously to self-assemble into highly ordered polyPro II-like triple-helical structures when dissolved in aqueous subphases. In the present study, we have examined peptide-amphiphiles containing monoalkyl chain tails for similar self-assembly behaviors. The structure of a collagen-model peptide has been characterized with and without an N-terminal hexanoic acid (C6) modification. Evidence for a self-assembly process of both the peptide and peptide-amphiphile has been obtained from (a) circular dichroism spectra and melting curves characteristic of triple-helices, (b) one-dimensional NMR spectra indicative of stable triple-helical structure at low temperatures and melted triple helices at high temperatures, and (c) pulsed-field gradient NMR experiments demonstrating different self-diffusion coefficients between proposed triple-helical and non-triple-helical species. The peptide-amphiphile appeared to form monomeric triple helices. The thermal stability of the collagen-like structure in the peptide-amphiphile was found to increase as the monoalkyl tail chain length is increased over a range of C6 to C16. The assembly process driven by the hydrophobic tail, albeit monoalkyl or dialkyl, may provide a general method for creating well-defined protein molecular architecture. Peptide-amphiphile structures possessing these alkyl moieties have the potential to be used for biomaterial surface modification to improve biocompatibility or, by mimicing fusion of viral envelopes with cellular membranes, as drug delivery vehicles.

Synthesis of cationic hemicyanine dyes and their interactions with ionic surfactants

Cationic hemicyanine dyes, 1-methyl-4[4-(di- n-alkylamino)styryl] pyridinium betaines containing dialkyl chains in the range C 1 to C 4 were synthesized and characterized. The interactions of dyes with cationic surfactant, cetyltrimethylammonium bromide (CTAB) and an anionic surfactant, sodium dodecyl sulfate (SDS) were studied by measuring their visible absorption spectra as a function of surfactant concentration below and above their critical micelle concentrations. Owing to lower hydrophobicity of the dyes, the electrostatic interactions between the dyes and the surfactants seemed to play an important role in the penetration of the dyes into the surfactant micelles.

Hydrophobic interaction of amphiphilic hemicyanine dyes with cationic and anionic surfactant micelles

The hydrophobic interaction of amphiphilic hemicyanine dyes, i.e. (dimethylamino)stilbazolium butyl sulphonate (I) and (dihexylamino)stilbazolium butyl sulphonate (II) with cetyltrimethyl ammonium bromide (CTAB), a cationic surfactant and lithium dodecyl sulphate (LDS), an anionic surfactant, was studied through absorption spectra as a function of the concentration of surfactants above and below their critical micelle concentrations. The different lengths of dialkyl chains present on these dyes exhibited hydrophobic interaction with micelles of CTAB and LDS; as a result visible spectra of both the dyes exhibited red shifts of different magnitudes when the dye molecules were solubilized into micelles. The approximate number of dye molecules per micelle was also estimated at a particular concentration of each surfactant. The solubilization depends on the dilakyl chain length of the dye together with the nature of surfactant head groups.

Surface Coating of Liposomes with Hydrophobized Polysaccharides

Coating the outermost surface of a liposomal membrane with several different hydrophobized polysaccharides was investigated by fluorescence depolarization, gel chromatography, and dynamic light scattering methods. The binding of cholesterol-bearing pullulan to the liposomal surface was biphasic. The first process was finished within minutes while the subsequent slow stages took over several hours. The binding isotherms followed Langmuir-type adsorption. The binding constant (K) increased with increases in the substitution degree of the cholesteryl moiety and the molecular weight of the pullulan derivatives used, while the maximum amount of the polysaccharide coating (qs) was almost the same. The apparent liposome size increased by 20-30 nm upon coating. Chemical structure of the parent polysaccharide had only a slight effect on the binding constant, while the structures of the hydrophobic moiety had a significant effect on the coating behavior of the liposomes. In the case of dodecyl diglyceryl group-bearing pullulan, both K and qs were smaller than those of other cholesterol-bearing polysaccharides. The addition of hexadecyl-bearing pullulan to the liposome induced aggregation of the liposomes. The cholesteryl moiety is an excellent hydrophobic anchor for polysaccharide coating liposomal surfaces compared with simple monoalkyl or dialkyl chains.

Reorganisation of alkyl chains in vesicles formed in aqueous solution by dialkyldimethylammonium bromide, R2N+Me2Br- where R=C12H25, C14H29, C16H33 or C18H37

Differential scanning calorimetry (DSC) scans are reported for aqueous solutions containing vesicles formed by four dialkyl-dimethylammonium bromides; R 2 N + Me 2 Br - where R=dodecyl (DDAB), tetradecyl (DTAB), hexadecyl (DHAB) or octadecyl (DOAB). Electron micrographs of DTAB (aq; 2×10 -3 mol dm -3 ) confirmed that these solutions, prepared at 50°C, contain vesicles, with radii ca. 700 nm. DSC scans of these solutions, initially cooled to 5°C and then scanned with increasing temperature, showed no evidence of an extremum in isobaric heat capacity as a function of temperature, associated with a chain-packing transition in the vesicular bilayer at a characteristic temperature, T m . However, clear evidence for such a transition near 29°C was obtained after this solution had been held at 5°C for periods up to 11 h. With increase in the time during which the DTAB solution was held at 5°C, the recorded signal associated with the melting temperature increased in intensity. However, there was again no evidence for this transition if the solution was cooled to 5°C and the heat capacity dependence on temperature immediately re-scanned. The patterns are discussed in terms of a kinetic control, during cooling, of the packing of dialkyl chains in the bilayers. A similar pattern was observed for DDAB (aq) where T m =15.8°C. In the case of DHAB (aq) where T m =28.1°C, no kinetic features were apparent using DSC to study the gel to chain-packing transition.

A parallel molecular dynamics simulation code for dialkyl cationic surfactants

We have developed a new simulation code, COMFORT, for the study of assemblies of flexible surfactant molecules, structured for parallel execution and specialised to surfactants with dialkyl chain geometry. The approach is a hybrid domain-decomposition and systolic-loop algorithm which is suitable for systems composed of long chain molecules and with tens of thousands of atoms in total. The algorithm uses a modified Ewald technique for two dimensionally periodic systems which has been successfully parallelized. The code was designed to be highly portable between machines of different architectures. The code has been tested on a number of platforms including the Intel iPSC/860, the IBM SP1, the CRAY T3D, a SGI Power Challenge and a number of workstation clusters. We demonstrate that scalable parallel computing technology, combined with appropriate software, can provide a commercially viable simulation system for use in the exploration and development of surfactant assemblies.

Amphiphilic Poly(acrylamide)s Having Saturated and Unsaturated Dialkyl Chains and Phosphatidylcholine Groups in the Side Chains

A novel phosphatidylcholine analogous vinyl monomer 1-(acrylamidomethyl)-2'-(trimethyl ammonio)ethyl phosphate (AMP) was synthesized and characterized. A series of amphiphilic poly- (acrylamide)s were obtained from AMP, and some dialkylacrylamide monomers, by radical copolymeri- zation in the presence of R,R'-azobis(isobutyronitrile) (AIBN). The polyelectrolyte behavior of these copolymers was investigated by their viscosity measurements. Moreover, the structures in condensed phases and thermal properties of these copolymers were investigated by X-ray analysis, DSC measurement, and POM observation. In addition, the phase transitions of monolayers obtained from these amphiphilic copolymers were observed by changing the temperature of the subphase, length of the alkyl chains, and observation times (tob). The LB films were prepared by using the vertical dipping method, and their surface contact angles with pure water were also measured.

Self-Assembling Amphiphiles for Construction of Protein Molecular Architecture

Peptide-amphiphiles with collagen-model head groups and dialkyl chain tails have been synthesized and shown to self-assemble into highly ordered polyPro II like triple-helical structures when dissolved in aqueous subphases. Evidence for this self-assembly process has been obtained from (a) compression of stable peptide-amphiphile monolayers to molecular areas comparable with triple-helical areas, (b) circular dichroism spectra and melting curves characteristic of triple-helices, and (c) two-dimensional NMR spectra indicative of stable triple-helical structure at low temperatures and melted triple-helices at high temperatures. The thermal stability of the collagen-like structure in the peptide-amphiphile is substantially higher (ΔTm = 15−20 °C) than that of peptides without lipidation. The assembly process driven by the hydrophobic tail may provide a general method for creating well-defined protein molecular architecture using a minimalist peptide-based approach.

Naturally Occurring Surfactants and Their Functional Design

Characteristics of soaps, natural surfactants and bioemulsifiers as well as biosurfactants are reviewed and reevaluated as useful amphipathic materials in comparison with synthetic surfactants from petroleum origin. Then, new functions of microbial biosurfactants are inspected on polycarboxylic-type spiculisporic acid and agaricic acid, rhamnolipid A and B, cyclopeptide-type surfactin, and saponin-type aescin. Mimicking chemical structures of useful biosurfactants, biomimetic surfactants such as synthetic corynomycolic acid analogues having sole dialkyl chain structures and sophorolipid analogue having different hydroxyalkanoyl chain from microbial origin were prepared aiming at modification and improvement of original biosurfactants. There have been many hybrid-type chemical modifiers of pharmaceuticals with amphipathic moieties. Otherwise, chemical sensing or control release systems were aggressively constituted from liposomes consisting of pH-, reductant-, glucose- and chemical stimuli-sensi tive biomimetic surfactants as well as polysoap coat forming helical chains on liposomal surface.

Permeability-controllable membranes. Part 8. Electrical redox sensitive permeation through a multibilayer-immobilized film containing a ferrocenyl group as a redox site

Multibilayer-immobilized films containing a ferrocenyl group as a redox site at a hydrophobic alkyl chain (FeC11C18N+) or as a hydrophilic head group of bilayer-forming dialkylammonium amphiphiles (2C16N+Fc) have been prepared by ion-complexation with poly(styrenesulphonate)(PSS–). Redox reactions of ferrocene groups in multibilayer films (FcC11C18N+/PSS– and 2C16N+ Fc/PSS–) have been shown to occur only in the fluid state of bilayer matrices above their phasetransition temperatures (Tc= 35 and 26°C, respectively), as confirmed by cyclic voltammetry. The permeability of water-soluble, non-ionic fluorescent probes through the multibilayer film cast on a platinium minigrid sheet is enhanced by a factor of 2–5 by the electrochemical oxidation of a ferrocenyl unit in the fluid multibilayer film above its Tc, compared with that of the reduced form. Permeability could be changed reversibly over at least 20 cycles by repeated redox reactions in the case of the 2C16N+ Fc/PSS– film containing an Fc unit near the hydrophilic moiety. In contrast, the change in permeability of the FcC11C18N+/PSS– film with a redox site in the hydrophobic dialkyl chain became irreversible under continuous redox reactions.

Sensitivity and selectivity of compounds interacting with neuropathy target esterase: Further structure-activity studies

Assay of neuropathy target esterase (NTE) which accounts for about 70% of paraoxon-resistant phenyl valerate (PV) esterase activity of hen brain depends on the fact that it is selectively inhibited by mipafox. A previous study of structure/activity relationships ( Biochem. Pharmac. 24, 797, 1975) has been extended. Among 14 potential substrates NTE hydrolysed phenyl phenoxyacetate and phenyl thiophenoxyacetate faster (1.5–1.7×) than PV, but selectivity of these substrates for NTE among the paraoxon-resistant esterases was only 35–52%. Seventy-seven other potential inhibitors (organophosphates, phosphonates, phosphoramidates, phosphinates and carbamates) were examined to determine inte 50 and effects on both NTE and “non-NTE” at 3–4 × inte 50 ( i 85–95) and, where possible, at 6–20 × inte 50. Hydrophophic inhibitors with small/flexible leaving groups were generally very inhibitory: several 2,2-dichlorovinyl phosphates and fluorides were active at low nanomolar concentrations. In the dichlorovinyl phosphate series increasing dialkyl chain length beyond n-pentyl decreased inhibitory power, presumably due to steric hindrance since the methyl/ n-decyl ester was 15 × more active than di- n-decyl. Chloro-substitution of both ortho-positions of a phenyl leaving group for benzylcarbamates reduced inhibitory power more than 20 × but had little effect in a phenyl leaving group of methyl phenylphosphonates where the acyl-leaving group bond is longer and less subject to steric hindrance. N-phenylbenzohydroxamyl benzylcarbamate is 10 × more potent than any previously described carbamate against NTE. Among stereo-isomers differences of activity ranged from < 2- to 15-fold. Only diphenylphosphinyl fluoride appeared to be virtually specific for NTE: at 0.5–1 μM it inhibited ca. 92% of NTE and 10–13% of “non-NTE” which is similar to the specificity found for 2,6-dichlorophenyl methyl phenylphosphonate which has been claimed to be specific. Diphenylphosphinyl fluoride has an advantage in that it is easily synthesized and should be protective rather than neuropathic, but it is not stable in store. We cannot repeat experiments purporting to show a substantial proportion of a second isozyme of NTE. However, according to first-order kinetics, concentrations of inhibitor > 6 × i 50 should inhibit NTE >; 98% and for 19 out of 26 compounds a residue greater than 3% (limit of precision) was found under these conditions: in nearly every case the quantity was 3–5%. This quantity may not be “true NTE” but it cannot be the target for organophosphate-induced delayed neuropathy since it is resistant to various neuropathic and protective compounds. The error of including this “non-NTE” in assays using the standard protocol is negligible