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We present the structural and electrical property characterization of solution-deposited thin films of a self-organizing phthalocyanine 2,3,9,10,16,17,23,24-octa(2-(4-octylbenzamide ethyl-sulfanyl)...

The synthesis and materials properties of a new liquid crystalline phthalocyanine, octakis (2-benzyloxyethylsulfanyl) copper (II) phthalocyanine, 2, are reported. This phthalocyanine possesses eight benzyl-terminated side chains with thioether links to the Pc core, which promote greater interaction between the discotic mesogens than has been seen in previous Pcs reported from this group which had benzyl-terminated alkoxy-based side chains. The use of thioether links to these side chains promotes a red-shift in the Q-band absorbance spectrum, small decreases in first oxidation potential, increased solution aggregation constants, and significantly higher K→LC transition temperatures than seen in conventional alkoxy-based side-chain-modified Pcs. Powders and single crystals of this material were characterized by X-ray diffraction and found to represent two closely related polymorphs. Room-temperature XRD of powders of 2 showed a monoclinic unit cell: a = 22.81(1) A, b = 9.780(5) A, c = 19.314(6) A, α = 90°,...

The direct current (dc) conductivities and organic field-effect transistor (OFET) characteristics of a class of octa-substituted liquid crystalline (discotic mesophase) phthalocyanines (Pcs) are discussed. These molecules self-organize into columnar aggregates with large coherence lengths (up to approximately 300 nm). Langmuir–Blodgett films of these molecules were horizontally transferred to either interdigitated microelectrodes (IME) or OFET substrates, so that current flow could be measured either parallel or perpendicular to the column axis. Twenty-eight bilayer films of these Pcs on the IME substrates showed anisotropies in dc conductivity up to 50:1, whereas similar Pc films showed anisotropies in field effect mobilities of approximately 10:1, for a variety of W/L ratios (source/drain dimensions and spacing). Field-effect mobilities of 1 to 5 × 10-6 cm2·V-1·s-1 were determined from OFET measurements, along the Pc column axis, whereas charge mobilities measured from the space charge limited current regime on the IME substrates were in the range of 10-4 cm2·V-1·s-1. Conductive tip atomic force microscopy measurements on the apprximately 500-nm length scale showed that the conductivity anisotropy can be as high as 1000:1 when the Pc columns are intimately contacted to an adjacent Au bond pad.

We report here the synthesis, characterization, and thin film formation of a polymerizable octa-substituted phthalocyanine (Pc) with styryl-terminated side chains, CuPc(OCH2CH2OCH2CHCHPh)8, 2,3,9,10,16,17,23,24-octakis(2-cinnamyloxyethoxy) phthalocyaninato copper(II) (1). We compare this Pc with a previously discussed phthalocyanine, also possessing styryl groups at the termini of the side chains, but with one alkoxy group in the side chain removed, CuPc(OCH2CH2CHCHPh)8 (2) (J. Am. Chem. Soc. 2001, 123, 3595). Both 1 and 2 are related to the octa-substituted phthalocyanine CuPc(OCH2CH2OBz)8, 2,3,9,10,16,17,23,24-octakis (2-benzyloxyethoxy) phthalocyaninato copper(II) (3), which has been shown to form highly coherent rodlike aggregates in Langmuir−Blodgett (LB) films, with excellent control of rod orientation (J. Am. Chem. Soc. 1999, 121, 8628; Langmuir 2001, 17, 7071). Irradiation of the styryl π−π* absorbance bands (254 nm) for horizontally transferred LB films of 1 and 2 results in stabilization of thei...

The effect of peptide conformational constraint on the peptide permeation across the model membranes was examined by determining the permeability of pairs of cyclic and acyclic peptides related to c[d-Pen2, d-Pen5] enkephalin (DPDPE). The peptides were cyclized by formation of an intramolecular disulfide bridge between the second and fifth residues composed of either d-penicillamine or cysteine. In each case the acyclic peptide was three to seven times more permeable than corresponding cyclic peptide. The possibility that the differences in permeability of cyclic and acyclic peptides is based on the greater conformational freedom of the acyclic peptides in the presence of membrane was examined in more detail by isothermal titration calorimetric studies of Trp6-DPDPE and its acyclic analog. The membrane binding of the acyclic peptide is a more exothermic process than binding of its cyclic Trp6-DPDPE. The transfer of acyclic peptide from water to membrane is an enthalpy driven process, whereas the transfer of the cyclic peptide is driven by entropy.

Four enkephalin analogues (Tyr-D-Thr-Gly-Phe-Leu-Ser-CONH(2), 1, and the related O-linked glycopeptides bearing the monosaccharide beta-glucose, 2, the disaccharide beta-maltose, 3, and the trisaccharide beta-maltotriose, 4) were synthesized, purified by HPLC, and biophysical studies were conducted to examine their interactions with membrane model systems. Glycopeptide 2 has been previously reported to penetrate the blood-brain barrier (BBB), and produce potent analgesia superior to morphine in mice (J. Med. Chem.2000, 43, 2586-90 and J. Pharm. Exp. Ther. 2001, 299, 967-972). The parent peptide and its three glycopeptide derivatives were studied in aqueous solution and in the presence of micelles using 2-D NMR, CD, and molecular mechanics (Monte Carlo studies). Consistent with previous conformational studies on cyclic opioid agonist glycopeptides, it was seen that glycosylation did not significantly perturb the peptide backbone in aqueous solution, but all four compounds strongly associated with 5-30 mM SDS or DPC micelles, and underwent profound membrane-induced conformational changes. Interaction was also observed with POPC:POPE:cholesterol lipid vesicles (LUV) in equilibrium dialysis experiments. Although the peptide backbones of 1-4 possessed random coil structures in water, in the presence of the lipid phase they each formed a nearly identical pair of structures, all with a stable beta-turn motif at the C-terminus. Use of spin labels (Mn(2+) and 5-DOXYL-stearic acid) allowed for the determination of the position and orientation of the compounds relative to the surface of the micelle.

Planar supported lipid bilayers (PSLBs) composed of phosphorylcholine (PC) lipids are known to be highly resistant to nonspecific adsorption of soluble proteins. However, these structures lack the stability desired for implementation in molecular devices (e.g., biosensors). In part 1 of this report [Ross, E. E.; Spratt, T.; Liu, S.; Rozanski, L. J.; O'Brien, D. F.; Saavedra, S. S. Langmuir 2003, 19, 1752−1765], we described preparation and characterization of (poly)PSLBs composed of diene-functionalized lipids. Here we have examined nonspecific adsorption of bovine serum albumin (BSA) to these (poly)PSLBs and several reference surfaces, using total internal reflection fluorescence and atomic force microscopy. The results show that the protein resistance of a cross-linked (poly)PSLB composed of bis-sorbyl phosphatidylcholine (bis-SorbPC) is equivalent to that of a fluid PSLB composed of 1-palmitoyl-2-oleoylphosphatidylcholine, even after the former has been dried and rehydrated. Since the lipids in a (poly...

Although fluid lipid films have been used widely in biosensing devices, they lack the high stability desired for technological implementation because the noncovalent forces between the constituent lipids are relatively weak. In this work, polymerized, planar supported lipid bilayers ((poly)PSLBs) composed of diene-functionalized lipids have been prepared and characterized. Several parameters relating (poly)PSLB structure and stability to observations made in studies of polymerized bilayer vesicles were examined, including a comparison of UV photopolymerization and redox-initiated radical polymerization, the number and location of the polymerizable moieties in the lipid monomer, and a comparison to PSLBs produced with diacetylene lipids. Redox-initiated polymerization of films composed of bis-substituted diene lipids with at least one polymerizable moiety located near the acyl terminus produced dried PSLBs that were highly uniform and stable. All other conditions yielded PSLBs that contained a high density...

We have used an interfacial stress rheometer to study the changes in the mechanical shear properties of a Langmuir monolayer of a linear polymer with reactive side chains. The polymer investigated had a linear hydrophilicbackbone consisting of poly(ethylene imine-co-ethyl oxazoline) and contained 20% hydrophobic sorbyl side chains, making it amphiphilic and capable of forming stable monolayers at the air-water interface. The sorbyl moiety in the side chain was photopolymerizable at 254 nm. Upon exposure of the film to UV light, the surface dynamic shear modulus, G' s , which is a measure of the elasticity, increased 1000-fold to ∼2 mN/m. This large increase in elasticity arises from the formation of a network by reaction of side chains on different polymer backbones. Rubber-like properties were deduced from the frequency dependence of the moduli and from creep experiments, where elastic recoil could be observed upon removing the applied stress. Such a network could be formed over a wide range of surface pressures ranging from 5 to 25 mN/m. We investigated the cross-linking kinetics upon UV exposure as a function of temperature, initial surface pressure, and light intensity. We have developed a lumped kinetic model that agrees with the transient behavior of the storage modulus, our measure of the density of cross-link points. The reaction was independent of temperature (over 10-30 °C) and exhibited a first-order dependence on light intensity. Since the reactive side groups must be in close enough proximity for the interpolymer side chain reaction to occur, a threshold side chain density is required to form junction points. After extensive UV exposure, the elasticity of the network degraded, and the rate of degradation was faster for films polymerized at lower initial surface pressures.

Bicontinuous cubic (QII) phases composed of hydrated lipids are a unique mesoporous organic material. The diameter of the water channels in the range of 5-10 nm could be used as a reservoir for mac ...

According to the model for passive transport across the membranes, the total flow of permeant molecules is related to the product of the water–membrane partition coefficient and the diffusion coefficient, and to the water–membrane interfacial barrier. The effect of membrane surface charge on the permeability and interaction of analgesic peptide ligands with model membranes was investigated. A mixture of zwitterionic phospholipids with cholesterol was used as a model membrane. The lipid membrane charge density was controlled by the addition of anionic 1-palmitoyl-2-oleoylphosphatidylserine. Two classes of highly potent analgesic peptides were studied, c[ D -Pen 2 , D -Pen 5 ]enkephalin (DPDPE) and biphalin, a dimeric analog of enkephalin. The effect of increased surface charge on the permeability of the zwitterionic DPDPE is a relatively modest decrease, that appears to be due to a diminished partition coefficient. On the other hand the binding of the dicationic biphalin ligands to membranes increases proportionally with increased negative surface charge. This effect translates into a significant reduction of biphalin permeability by reducing the diffusion of the peptide across the bilayer. These experiments show the importance of electrostatic effects on the peptide–membrane interactions and suggest that the negative charge naturally present in cell membranes may hamper the membrane transport of some peptide drugs, especially cationic ones, unless there are cationic transporters present.

As part of a research effort to design and prepare high affinity ligands for the galactosyl ceramide (GalCer) binding site on the HIV cell surface glycoprotein, gp120, several GalCer analogues have been prepared and characterized. The molecular design of analogues permits independent variations of the carbohydrate, the length of a hydrophilic spacer between the ligand and the lipid, and the composition of the hydrophobic lipid chains. Five different galactosyl analogues were synthesized having hydrophilic spacers of tri-, tetra-, and penta-ethylene glycol separating the carbohydrate from the lipid region which has either oleoyl or stearoyl lipid chains. The synthetic design allows for a convergent synthesis of the three components of the glycolipid conjugate. The structural characterization includes the proton and carbon chemical shifts, which were assigned after analysis of 1D and 2D NMR spectra.

We present here a study of the effects of surface modification on the efficiency of transfer of ultrathin Langmuir−Blodgett films of rodlike aggregates of the phthalocyanine (Pc) (2,3,9,10,16,17,23,24-octakis((2-benzyloxy)ethoxy)phthalocyaninato)copper (1) to gold and silicon substrates. These surface modifications impact on (i) the molecular orientation of the individual Pcs within the rodlike aggregates, (ii) the coherence of the aggregates (providing for coherence lengths of some Pc rods of over 100 nm), and (iii) the optical anisotropy and the overall uniformity and lack of pinholes in Pc bilayer films, on the 100 μm distance scale. Methyl-terminated and phenyl-terminated surface modifiers were added to both Au and Si surfaces through thiol and silane chemistries, respectively. The phenyl-terminated modifier for Au surfaces, benzyloxyethanethiol, 2, mimics the side chain composition of Pc 1. Both methyl- and phenyl-terminated modifiers produced hydrophobic surfaces, as revealed by high water contact a...

Hydrated lipid structures, such as liposomes, that display tethered metal-ion-chelating groups have proven useful in peptide and protein binding, as well as 2D protein crystallization through molecular recognition of accessible histidine sites in proteins and peptides. Polymerizable metal-ion-chelating lipids bearing a reactive diacetylene group have been described. These interesting compounds can be polymerized in the solid-analogous phase. Here we describe the design of the first polymerizable metal-ion-chelating lipid that can be used in the fluid, i.e., liquid analogous, phase of lipid bilayers. The synthesis of 1-palmitoyl-2-[8-[(E,E)-2',4'-hexadienoyloxy]octanoyl]-sn-glycero-3-N-[11-[N',N'-bis[carboxymethyl]imino]-3,6,9-trioxaundecanoyl] phosphatidylethanolamine (1) is described. The chelator moiety, iminodiacetate (IDA), was linked to the polymerizable phosphatidylethanolamine (PE) with a terminal 2,4-hexadienoyl (sorbyl) group through an oligo(ethylene glycol)-based spacer. Lipid 1-Cu complex is designed to be combined with the corresponding polymerizable matrix lipids (bis-SorbPC) to form functionalized liposomes that can be stabilized by various polymerization methods.

The cross-linking of supramolecular assemblies of hydrated amphiphiles is an effective method to stabilize the assembly. A well-known strategy for cross-linking of lipids in lyotropic phases is the...

In recent years several groups have described methods to prepare and utilize poly(ethylene glycol) conjugated phosphatidylethanolamine (PEG-PE) to sterically stabilize liposomes in order to avoid u...

Poly(ethylene glycol) (PEG)-stabilized liposomes were recently shown to exhibit differences in cell uptake that were linked to the liposome charge. To determine the differences and similarities between charged and uncharged PEG-decorated liposomes, we directly measured the forces between two supported, neutral bilayers with terminally grafted PEG chains. The measurements were performed with the surface force apparatus. The force profiles were similar to those measured with negatively charged PEG conjugates of 1, 2-distearoyl-sn-glycero-3-phosphatidyl ethanolamine (DSPE), except that they lacked the longer ranged electrostatic repulsion observed with the charged compound. Theories for simple polymers describe the forces between end-grafted polymer chains on neutral bilayers. The force measurements were complemented by surface plasmon resonance studies of protein adsorption onto these layers. The lack of electrostatic forces reduced the adsorption of positively charged proteins and enhanced the adsorption of negatively charged ones. The absence of charge also allowed us to determine how membrane charge and the polymer grafting density independently affect protein adsorption on the coated membranes. Such studies suggest the physical basis of the different interactions of charged and uncharged liposomes with proteins and cells.

We review here the self-assembly, electrochemical and spectroelectrochemical properties of 2,3,9,10,16,17,23,24-octa(2-benzyloxyethoxy) phthalocyaninato copper ( CuPc ( OC 2 OBz )8), where terminal benzyl groups on the eight ethylene oxide side chains assist in forming unusually ordered, mechanically rigid thin films. New spectroscopic characterization of cast CuPc ( OC 2 OBz )8 films is discussed in comparison with cast films of its metal-free analogue H 2 Pc ( OC 2 OBz )8 and similar copper and dihydrogen phthalocyanines with benzyl — terminated triethylene oxide substituents, CuPc (( OC 2 O )3 Bz )8, and H 2 Pc (( OC 2 O )3 Bz )8, which do not demonstrate the same degree of ordering as CuPc ( OC 2 OBz )8. AFM studies of horizontally transferred LB films of CuPc ( OC 2 OBz )8 show column–column distances of ca 2.8 nm and confirm the high degree of ordering previously surmised from spectroscopic characterization of multilayer thin films. The oxidative electrochemistry of multilayer thin films prepared from these Pcs is strongly dependent on the chemical identity of the supporting electrolyte anion and on annealing of the thin films. Compliance of the films to counter-ion transport limits the extent of electrochemical doping. Preliminary studies of the oxidative electrochemistry of isolated CuPc ( OC 2 OBz )8 aggregates (diluted into an electroinactive methyl arachidate thin film) on an electroactive, integrated optic waveguide (EA-IOW) are also presented. Monitoring the change in absorbance at 633 nm on the waveguide surface allows the determination of the onset potential for oxidation of the isolated aggregates, which appears to be less positive in potential versus that observed for multilayer Pc assemblies.

Phthalocyanines (Pc) modified at eight positions with benzyloxyethoxy groups (CuPc(OC2OBz)8 and H2Pc(OC2OBz)8) form discotic mesophases in the bulk and self-assemble into cofacial rodlike aggregates in monolayers. These Pc aggregates form close packed arrays which are simple to process into highly coherent multilayer thin films. When these self-organizing molecular systems are compressed on the surface of an LB trough, the Pc columns align parallel to the compression barriers and form a rigid bilayer film (ca. 5.6 nm thick). Sections of these bilayer films can be mechanically removed from the trough surface with complete retention of integrity of the remaining film. This unprecedented behavior appears to arise from the multiple π−π interactions between adjacent Pcs, resulting in unusually strong noncovalent interactions. AFM and STM studies of monolayer and bilayer films show that they consist of Pc columns which are coherent over distances of 50−100 nm. Thin films consisting of up to 15 bilayers (ca. 84 ...

The cross-linking polymerization of hydrated amphiphiles in monolayers, bilayers, and nonlamellar phases, i.e., bicontinuous cubic and the inverted hexagonal phases, is an effective method to modify their properties. Polymerization of monomeric amphiphiles in an assembly proceeds in a linear or cross-linking manner depending on the number and location of polymerizable groups per monomer. Polymerization of hydrated lipids with reactive groups in each hydrophobic tail yields cross-linked polymers. Sisson et al. (1996) examined the cross-linking of bilayers as a function of the mole fraction of bis-substituted lipids (bis-SorbPC), where the reactive groups were located at the end of the lipid tails. The onset of cross-linking was determined by changes in lipid lateral diffusion, bilayer vesicle stability, and polymer solubility. These data indicated that a substantial mole fraction (0.30 ± 0.05) of the bis-substituted lipid was necessary for bilayer cross-linking. Analysis of the cross-linking and competing ...

Hydrated amphiphiles can yield quite complex lyotropic liquid crystals such as the lamellar (bilayer) and nonlamellar phases. Lamellar structures can be solidlike or liquid crystalline. An important characteristic of these lamellar phases is the lateral diffusion of the lipids which increases by ca. 102 at the main phase transition, Tm. The rate (Rp) and degree (Xn) of polymerization were determined for polymerizable lipids in these two phases. A determination of the effect of temperature between 25 and 45 °C on the Rp of redox-initiated polymerization of mono-SorbPC bilayers showed a discontinuity near the Tm. The calculated activation energy, Ea, and frequency factor, A, for the polymerization at temperatures below Tm are 10 kcal/mol and 107, respectively. A similar calculation for the polymerization at temperatures above the Tm gave an Ea = 24 kcal/mol and A = 1016. The degree of polymerization, relative to poly(methyl methacrylate) standards, for bilayers of mono-SorbPC at temperatures above and below...

Technological applications of lipids may be possible through stabilization of various liquid-crystalline phases. One important approach to stabilized self-assembling materials utilizes polymerization of liquid-crystalline phases composed of reactive lipids. Polymerization of lipids has been utilized to modify the chemical and physical properties of lamellar assemblies (e.g., lipid monolayers, multilayers, and bilayer vesicles). In addition, polymerization of the lipid region of three-dimensional nonlamellar lipid-phase structures has recently been reported, including the reversed bicontinuous cubic (QII) phase, belonging to the space group Pn3m and the reversed hexagonal (HII) phase. Here we show that an easily prepared polymerizable monoacylglycerol combined in a 9/1 molar ratio with the corresponding polymerizable 1,2-diacylglycerol forms nonlamellar phases upon hydration at room temperature. Phase investigation using cross-polarized light, 2H NMR spectroscopy, and X-ray diffraction showed that the lipi...

The reactivity of polymerizable amphiphiles in supramolecular assemblies, such as lipid bilayers, is dependent on the mode of initiation, the polymerizable group, and the position of the reactive group in the amphiphile. This report describes the synthesis, characterization, and polymerization of a novel heterobifunctional lipid, 1-palmitoyl-2-(2,4,12,14-tetraenehexadecanoyl)phosphatidylcholine (1), that contains a diene and a dienoyl group in the sn-2 acyl chain. The difference in polarity of local sites of each group within the bilayer makes it possible to perform simultaneous or selective polymerizations of these groups. Simultaneous polymerization of both reactive groups was achieved by either redox polymerization or direct photoirradiation. Selective polymerization of the dienoyl was accomplished by photoirradiation with filtered light from a high-pressure Hg/Xe lamp. The diene was selectively initiated by thermal decomposition of AIBN. The degree of polymerization depended strongly on the initiation...

Spectroscopic, electrochemical and spectroelectrochemical, and scanning probe microscopic characterization of thin films of (2,3,9,10,16,17,23,24-Octakis((2-benzyloxy)ethoxy)phthalocyaninato)copper...

Since the first reports of the polymerization of hydrated bilayers in the early 1980s, a wide variety of polymerizable groups and lipids has been successfully employed. Among the various strategies explored for the polymerization of lamellar phases, a particularly useful method relies on the design of suitable polymerizable amphiphiles, which upon hydration form assemblies that can then be polymerized with retention of structure. We have recently extended this strategy to successfully polymerize the inverted hexagonal (H II ) phase. This report is the first comparison of radical chain polymerizations in lamellar and H II phases. The number average degree of polymerization of polymers obtained in both lamellar and H II phases depended strongly on the initiation chemistry, but were insensitive to the lipid phases. The immediate benefit of these studies is the knowledge that polymer size can be varied extensively in both phases in order to obtain different materials properties.

Biphalin, (Tyr– d -Ala–Gly–Phe–NH) 2 , is a highly potent dimeric analog of enkephalin. Its analgesic efficacy is due in part to its ability to permeate the blood–brain barrier. To aid in understanding the mechanism of the transmembrane movement we determined and analyzed the permeability and partition coefficients of biphalin and a series of analogues where F, Cl, I, NO 2 , or NH 2 were placed in the para position of the aromatic rings of Phe 4,4′ . Liposomes composed of neutral phospholipids and cholesterol were used as the model membrane. The overall good correlation between permeability and water-membrane partition coefficients suggests that the movement of biphalins across the model membrane is controlled by diffusion and depends on the water-membrane partition coefficient. To explain the observed correlation between permeability and the electron withdrawing/donating character of the substituents in the phenylalanine ring, we examined various folding patterns of Leu–enkephalin, an endogenous pentapeptide that exhibits affinities toward the same classes of opioid receptors (δ and μ). The observed permeabilities and partition coefficients of biphalin and analogues, as well as the tyrosine side chain accessibility, are consistent with the presence of the type of folding where the tyrosine and phenylalanine side chains are in a close contact. We propose that the aromatic ring interaction can promote the peptide permeability by stabilizing a more compact structure of biphalin that would minimize the number of hydrogen bonds with water and therefore enhances partitioning into the model membrane.

Block copolymers and amphiphile/water systems both exhibit very rich polymorphism. The bicontinuous cubic morphologies mediate the transformation from a lamellar phase to a hexagonally-packed cylinder phase. However, certain bicontinuous cubic morphologies can theoretically transform smoothly (without disruption or tearing) to other bicontinuous cubic morphologies in response to variation in temperature and concentration. These bicontinuous phases are best understood in terms of their associated minimal surfaces. The minimal surfaces D (i.e, ordered bicontinuous double diamond OBDD for block copolymer; cubic phase Q224 for amphiphile/water system), G (i.e., gyroid G* for block copolymer; cubic phase Q230 for amphiphile/water system), and P (cubic phase Q229 for amphiphile/water system; not yet reported for block copolymers) were computed and their two-dimensional projections on the plane reveals various 4-fold and 3-fold symmetries that are at times indistinguishable from that of the hexagonal phase. More...

The hydration of polar natural and synthetic lipids yields a variety of lipid phases including various inverted cubic phases and the inverted hexagonal (HII) phase. The HII phase can be considered as aqueous columns encased with a monolayer of lipids and arranged in a hexagonal pattern. The polar head groups are well-ordered at the water interface, whereas the lipid tails are disordered to fill the volume between the tubes of water. A particularly interesting characteristic of the HII phase is the large temperature effect on the basis vector length d of the hexagonal lattice. Previous studies indicate that polymerization of the lipid region of the HII phase might reduce the sensitivity of the basis vector to temperature. A phosphoethanolamine (PE) was designed and synthesized with dienoyl groups in each lipid tail in an attempt to cross-link the lipids around and along the water core of the HII phase. The synthesis of the the PE was accomplished by acylation of 3-(4-methoxybenzyl)-sn-glycerol with 2,4,13-...

The sensitized polymerization of synthetic lipid bilayers via visible-light irradiation of membrane-bound cyanine dyes is reported. Visible-light-initiated polymerizations were successful with liposomes composed solely or partly of either 1-palmitoyl-2-[10-(2‘,4‘-hexadienoyloxy)decanoyl]-sn-glycero-3-phosphatidylcholine (mono-SorbPC), 1,2-bis[10-(2‘,4‘-hexadienoyloxy)decanoyl]-sn-glycero-3-phosphatidylcholine (bis-SorbPC), or 1,2-bis(2,4-octadecadienoyl)-sn-glycero-3-phosphatidylcholine (DenPC). The ballasted sensitizing dyes reported here were conveniently incorporated into liposomes. The sensitizing dye N,N‘-dioctadecyl-3,3,3‘,3‘-tetramethylindocarbocyanine perchlorate, DiIC(18)3, was used in many of these studies because its absorption properties were especially well matched to the spectral output of the light source. The lipid product from the sensitized photoconversion of mono-SorbPC was transesterified and analyzed by size exclusion chromatography, which revealed the presence of a polymer with a rel...

The synthesis and solution and thin film characterization of four octasubstituted phthalocyanines (Pcs) are reported. [2,3,9,10,16,17,23,24-octakis(dodecylcarboxylato)phthalocyaninato]copper, [2,3,...

Polymerization of monomeric lipids in an assembly proceeds in a linear or cross-linking manner depending on the number of polymerizable groups per monomeric lipid. Lipids that contain a single reactive moiety in either of the hydrophobic tails or associated with the hydrophillic head group yield linear polymers. Polymerization of lipids with reactive groups in each hydrophobic tail generally yield cross-linked polymeric networks. This report describes three approaches to the characterization of the gel point for polymerizations constrained by the two-dimensional nature of lipid bilayers. The gel point for two-dimensional lipid assemblies was determined by correlation of the onset of significant changes in the physical properties of the polymerized bilayers with the bilayer composition. The properties examined in this study were the lateral diffusion of a small molecule probe of the bilayer, the stability of polymerized bilayer vesicles in the presence of surfactants, and the solubility of lipid polymers i...

The first chemical syntheses of polymerizable monoacylglycerol and 1,2-diacyl-sn-glycerol are reported. The monodienoylglycerol is obtained in 80% yield from 1,2-O-isopropylidene-sn-glycerol and dienoyl fatty acid. The dienoic acid is accessible in 60% yield from the base-catalyzed hydrolysis of dienoyl ester, which is synthesized from the Wittig−Horner reaction of aldehyde and trimethyl 4-phosphonocrotonate. The acylation is carried out in the presence of 4-(dimethylamino)pyridine and dicyclohexylcarbodiimide. The use of excess protected glycerol relative to fatty acid affords the acylated product in high yield. The final step is the deprotection of isopropylidene group using dilute HCl solution. The 1,2-diacyl-sn-glycerol is synthesized by acylation of 3-(4-methoxybenzyl)-sn-glycerol with dienoyl fatty acid in the presence of 4-(dimethylamino)pyridine and dicyclohexylcarbodiimide. The removal of the 4-methoxybenzyl group by dimethylboron bromide catalyzed hydrolysis is especially useful in the synthesis...

The first chemical synthesis of a 1,2-bis-substituted polymerizable-sn-glycerol-3-phosphoethanolamine is reported. The synthetic approach utilizes the preparation of 1,2-bis(16-methy 1-2,4-(E,E)-octadecadienoyl)-3-(4-methoxybenzyl)-sn-glycerol via the acylation of 3-(4-methoxybenzyl)-sn-glycerol with 16-methyl-2,4-(E,E)-octadecadienoic acid. The deprotection of the 4-methoxybenzyl ether group is accomplished in high yield via Lewis acid catalyzed hydrolysis at −78°C. The final step is the phosphorylation of this 1,2-bis(dienoyl)-sn-glycerol.

A three component, liposome-bound photochemical molecular device (PMD) consisting of energy and electron transfer reactions is described. Bilayer membrane surface-associated dyes, 5,10,15,20-tetrakis[4-(trimethylammonio)-phenyl]-21H,2 3H-porphine tetra-p-tosylate salt and N,N[prime]-bis[(3-trimethylammonio)propyl]thiadicarbocya nine tribromide, are the energy donor and acceptor, respectively, in a blue light stimulated energy transfer reaction along the vesicle surface. The electronically excited cyanine is quenched by electron transfer from the phospholipid membrane bound triphenylbenzyl borate anion, which is located in the lipid bilayer interior. The PMD exhibits sequential reactions following electronic excitation with the novel feature that the steps proceed with orthogonal orientation: energy transfer occurs parallel to the membrane surface, and electron transfer occurs perpendicular to the surface. Photobleaching and fluorescence quenching experiments verify the transfer reactions, and Stern-Volmer analysis was used to estimate the reaction rate constants. At the highest concentrations examined of energy and electron acceptor ca. 60% of the photoexcited porphyrins were quenched by energy transfer to the cyanine. 56 refs., 6 figs., 3 tabs.

A systematic study of the effect of monomer [M] and initiator [I] concentration on the rate of polymerization, R p , for bilayers of acryloyl- and methacryloyl-substituted lipids is described. Both the polymerizations of an acryloyl- (AcrylPC) and methacryloyl-substituted phosphatidylcholinemono (MethPC) bilayers exhibit a R p dependenece on [M] and [I] 0.5 at the start of the polymerization, which indicates the bilayer-constrained polymer chains terminate by chain coupling and/or chain disproportionation. As the the polymerization approaches high conversion, the kinetic behavior changes

The reactivity of polymerizable amphiphiles in the two-dimensional matrix of supramolecular assemblies, such as lipid bilayers, is dependent on the monomer structure, the mode of initiation, the monomer to initiator ratio, and the lateral diffusion of the monomer within the assembly. As part of a study of these factors, we examined the thermally initiated polymerization and the photopolymerization of SorbPCs. The AIBN-initiated polymerization of hydrated bilayers of 1-palmitoyl-2-[10-(2',4'-hexadienoyloxy)decanoyl]-sn-glycero-3-phosphocholine (mono-SorbPC) or 1,2-bis[10-(2',4'-hexadienoyloxy)-decanoyl]-sn-glycero-3-phosphocholine (bis-SorbPC) at 60 o C produced linear and cross-linked polymers, respectively. In each case the polymers were transesterified to remove the lipid head group and yield linear copolymers composed of random repeat units of methyl sorbate and methyl carboxynonanyl sorbate, which were soluble in tetrahydrofuran and analyzed by size-exclusion chromatography relative to PMMA standards. The 1 H-NMR spectra of the transesterified polymers indicated the structures were 1,4-polymers. The number-average relative degree of polymerization (X n ) ranged from 50 to nearly 600 and was proportional to [I] -1 . These results, which suggest that chain termination at high conversion of SorbPC to polymer is dominated by primary termination, are similar to the behavior of acryloyl-substituted lipids (AcrylPC) in bilayers. The poly(AcrylPC)s were 4 times larger than poly(SorbPC)s at a given ratio of monomer to initiator. This is likely due to greater resonance stabilization of the sorbyl radical compared to the acryloyl radical. The photoreaction of SorbPC bilayers appears to be a singlet-mediated process, which produced oligomers at temperatures >T m . The rate of the photoreaction was directly proportional to the incident light intensity in a manner consistent with photoactivated addition

This report describes the initial characterization of supramolecular morphology of diacetylenic aldonamides where the headgroup has been systematically varied from hexose, pentose, to tetrose. The electron-dense diacetylenes allow direct electron microscopic imaging of the assembly morphology without the aid of staining reagents. The electron micrographs reveal a dramatic change in supramolecular morphology upon the simple changing the headgroup from D-galactose to L-arabinose. Possible reasons for the change in morphology are discussed.

NMR spectroscopic, peptide-membrane conformational studies on [D-Pen2,D-Pen5]-enkephalin (DPDPE), an opioid receptor selective peptide, and an acyclic analog of DPDPE (DPDPE reduced at the disulfide bond) were conducted. The NMR method of transferred nuclear Overhauser effect (TRNOE) was used to obtain NOE profiles of the free and membrane bound forms of DPDPE and acyclic DPDPE. After comparison of the profiles of both peptides in the free and membrane-bound states, we hypothesize that the cyclic DPDPE undergoes little if any conformational change upon interaction with the membrane. However, for the acyclic analog, large changes in the NOE profile associated with backbone and side-chain groups were observed after interaction with the membrane. Results of computerized molecular modeling studies also were consistent with our theory that the free and membrane-bound forms of cyclic DPDPE have very similar free and membrane-bound states. The free acyclic DPDPE has a reverse turn conformation with sidechains situated so that hydrophobic surface exposure to aqueous solution is minimized. After membrane interaction, the acyclic DPDPE has an extended conformation near the carboxy terminus with aromatic sidechains widely separated. We propose that the interaction of the acyclic DPDPE with the membrane surface is mediated by the amino terminus. We further propose that the interaction of the cyclic DPDPE with the membrane surface is limited because the D-Pen2 side chain is covalently bonded and the aromatic side chains and backbone are only slightly altered after membrane contact. Permeability studies by Ramaswami et al. [(1992) Biochim. Biophys. Acta 1109(2), 195-202] demonstrated that the acyclic DPDPE permeated through membranes at a rate 4 times greater than cyclic DPDPE. We conclude that conformational and topographical flexibility may be critical factors in peptide-membrane interactions and permeability of bilayer membranes to opioid peptides.

The titrametric addition of hydrophobic borate anions to water-soluble cationic cyanine dyes readily perturbs the dye visible absorption spectrum. The insensitivity of the spectral effect to the oxidation potential of the borate indicates that this interaction is not a charge-transfer complex. Both concentration and solvent dependencies suggest the effect is due to the formation of cyanine dye-borate complexes, which are driven primarily by the hydrophobicity of the borate. Thus, in water, the hydrophobic borate anion-dye interaction reduces the dye solubility with the concomitant formation of dimers of the cyanine dye-borate complexes that facilitate electronic interactions of the dye

The thermotropic phase behavior of hydrated bilayers of mono- and bis-substituted phosphatidylcholines (PC) containing either acryloyl, methacryloyl, or sorbyl ester groups at the chain terminus was studied by differential scanning calorimetry. Each of these compounds exhibits a single endotherm which occurs at a temperature lower than that of the main phase transition T m of the corresponding linear saturated chain PC. Variation of the chain length of the sorbylPCs results in a pronounced odd/even alternation of the T m . Consideration of the preferred conformation of glycerol ester lipids suggested by the crystal structure of dimyristoylPC dihydrate provides a basis for understanding the odd/even effect reported here

A successful strategy for the self-assembly and stabilization of a substrate-supported, phospholipid bilayer is described. The bilayer is self-organized by fusion of fluid vesicles, composed of bis-sorbylphosphatidylcholine, on an oxide surface. The supported bilayer is then polymerized in situ to produce a cross-linked structure that is stable to surfactant solutions, organic solvents, and to transfer across the air/water interface, yet retains the resistance to nonspecific protein adsorption characteristic of a fluid phosphatidylcholine bilayer.

The first chemical syntheses of polymerizable monoacylglycerol and 1,2-diacyl-sn-glycerol are reported. The monodienoylglycerol is obtained in 80% yield from 1,2-O-isopropylidene-sn-glycerol and dienoyl fatty acid. The dienoic acid is accessible in 60% yield from the base-catalyzed hydrolysis of dienoyl ester, which is synthesized from the Wittig−Horner reaction of aldehyde and trimethyl 4-phosphonocrotonate. The acylation is carried out in the presence of 4-(dimethylamino)pyridine and dicyclohexylcarbodiimide. The use of excess protected glycerol relative to fatty acid affords the acylated product in high yield. The final step is the deprotection of isopropylidene group using dilute HCl solution. The 1,2-diacyl-sn-glycerol is synthesized by acylation of 3-(4-methoxybenzyl)-sn-glycerol with dienoyl fatty acid in the presence of 4-(dimethylamino)pyridine and dicyclohexylcarbodiimide. The removal of the 4-methoxybenzyl group by dimethylboron bromide catalyzed hydrolysis is especially useful in the synthesis...

The titrametric addition of hydrophobic borate anions to water-soluble cationic cyanine dyes readily perturbs the dye visible absorption spectrum. The insensitivity of the spectral effect to the oxidation potential of the borate indicates that this interaction is not a charge-transfer complex. Both concentration and solvent dependencies suggest the effect is due to the formation of cyanine dye-borate complexes, which are driven primarily by the hydrophobicity of the borate. Thus, in water, the hydrophobic borate anion-dye interaction reduces the dye solubility with the concomitant formation of dimers of the cyanine dye-borate complexes that facilitate electronic interactions of the dye

Since the first reports of the polymerization of hydrated bilayers in the early 1980s, a wide variety of polymerizable groups and lipids has been successfully employed. Among the various strategies explored for the polymerization of lamellar phases, a particularly useful method relies on the design of suitable polymerizable amphiphiles, which upon hydration form assemblies that can then be polymerized with retention of structure. We have recently extended this strategy to successfully polymerize the inverted hexagonal (H II ) phase. This report is the first comparison of radical chain polymerizations in lamellar and H II phases. The number average degree of polymerization of polymers obtained in both lamellar and H II phases depended strongly on the initiation chemistry, but were insensitive to the lipid phases. The immediate benefit of these studies is the knowledge that polymer size can be varied extensively in both phases in order to obtain different materials properties.