Homochiral oligopeptides by chiral amplification within two-dimensional crystalline self-assemblies at the air-water interface; relevance to biomolecular handedness

A possible role that might have been played by ordered clusters at interfaces for the generation of homochiral oligopeptides under prebiotic conditions has been probed by a catalyzed polymerization of amphiphilic activated alpha-amino acids, in racemic and chiral non-racemic forms, which had self-assembled into two-dimensional (2D) ordered crystallites at the air-aqueous solution interface. As model systems we studied N(epsilon)-stearoyl-lysine thioethyl ester (C(18)-TE-Lys), gamma-stearyl-glutamic thioethyl ester (C(18)-TE-Glu), N(alpha)-carboxyanhydride of gamma-stearyl-glutamic acid (C(18)-Glu NCA) and gamma-stearyl-glutamic thioacid (C(18)-thio-Glu). According to in-situ grazing incidence X-ray diffraction measurements on the water surface, (R,S)-C(18)-TE-Lys, (R,S)-C(18)-TE-Glu, and (R,S)-C(18)-Glu-NCA amphiphiles self-assembled into ordered racemic 2D crystallites. Oligopeptides 2-12 units long were obtained at the air-aqueous solution interface after injection of appropriate catalysts into the water subphase. The experimental relative abundance of oligopeptides with homochiral sequence generated from (R,S)-C(18)-TE-Lys and (R,S)-C(18)-TE-Glu, as determined by mass spectrometry on enantioselectively deuterium-labeled samples, was found to be significantly larger than that obtained from (R,S) C(18)-thio-Glu which polymerizes randomly. An efficient chiral amplification was obtained in the polymerization of non-racemic mixtures of C(18)-Glu-NCA since the monomer molecules in the racemic 2D crystallites are oriented such that the reaction occurs between heterochiral molecules related by glide symmetry to yield heterochiral oligopeptides whereas the enantiomer in excess, in the enantiomorphous crystallites, yield oligopeptides of a single handedness.     

Homochiral oligopeptides generated by induced "mirror symmetry breaking" lattice-controlled polymerizations in racemic crystals of phenylalanine N-carboxyanhydride

The formation of diastereoisomeric libraries of oligopeptides through the heterogeneous polymerization of racemic crystals of phenylalanine N-carboxyanhydride (PheNCA) is reported. The diastereoisomeric compositions of the oligopeptides formed on polymerization of (R,S) crystals incorporating the deuterium-tagged S enantiomer were determined by MALDI-TOF mass spectrometry. The racemic mixtures of the oligopeptides longer than pentamers are represented primarily by diastereoisomers of homochiral sequence and with peptides containing only one heterochiral repeating unit. A mechanism comprising the following three sequential steps to account for this unusual observation is proposed: 1) formation of dimers and trimers at a partially damaged liquid/solid interface, 2) chain propagation that takes place within the bulk of the crystal through a lattice-controlled "zipper-like" mechanism between homochiral molecules arranged in a head-to-tail motif to yield crystalline antiparallel beta-sheets of alternating oligopeptide chains of homochiral sequence of opposite handedness, and 3) enantiomeric cross-inhibition that results in chain termination. Induced desymmetrization of the racemic mixtures of the formed peptides was achieved by the polymerization of the mixed quasi-racemic crystals of (R)-PheNCA, ((S)-PheNCA), and (S)-ThieNCA (3-(2-thienyl)-alanine N-carboxyanhydride) of various compositions. These experiments resulted in the formation of nonracemic libraries of oligopeptides composed of homochiral chains of (R)-Phe and copolymers of randomly distributed (S)-Phe and (S)-Thie sequences. From these findings, we propose a stochastic model for the generation of libraries of nonracemic mixtures of oligopeptides from the polymerization of host (R,S)-PheNCA with racemic mixtures of other guest NCA amino acids dissolved in limited quantities in the crystal.     

Oligopeptides and copeptides of homochiral sequence, via beta-sheets, from mixtures of racemic alpha-amino acids, in a one-pot reaction in water; relevance to biochirogenesis

As part of our studies on the biochirogenesis of peptides of homochiral sequence during early evolution, the formation of oligopeptides composed of 14-24 residues of the same handedness in the polymerization of dl-leucine (Leu), dl-phenylalanine (Phe), and dl-valine (Val) in aqueous solutions, by activation with N, N'-carbonyldiimidazole and then initiation with a primary amine, in a one-pot reaction, was demonstrated by MALDI-TOF MS using deuterium enantio-labeled alpha-amino acids. The formation of long isotactic peptides is rationalized by the following steps occurring in tandem: (i) creation of a library of short diasteroisomeric oligopeptides containing isotactic peptides in excess in comparison to a binomial kinetics, as a result of an asymmetric induction exerted by the N-terminal residue of a given handedness; (ii) precipitation of the less soluble racemic isotactic penta- and hexapeptides in the form of beta-sheets that are delineated by homochiral rims; (iii) regio-enantiospecific chain elongation occurring heterogeneously at the beta-sheets/solution interface. Polymerization of l-Leu with l-isoleucine (Ile) or l-Phe with l- (1) N-Me-histidine yielded mixtures of copeptides containing both residues. In contrast, in the polymerization of the corresponding mixtures of l- + d-alpha-amino acids, the long oligopeptides were composed mainly from oligo- l-Leu and oligo- d-Ile in the first system and oligo- d-Phe in the second. Furthermore, in the polymerization of mixtures of hydrophobic racemic alpha-amino acids dl-Leu, dl-Val, and dl-Phe and with added racemic dl-alanine and dl-tyrosine, copeptides of homochiral sequences are most dominantly represented. Possible routes for a spontaneous "mirror-symmetry breaking" process of the racemic mixtures of homochiral peptides are presented.     

Racemic beta-sheets as templates for the generation of homochiral (isotactic) peptides from aqueous solutions of (RS)-valine or -leucine N-carboxy- anhydrides: relevance to biochirogenesis

As part of our program on biochirogenesis of homochiral peptides from racemic precursors, we report the feasibility of obtaining peptides with homochiral sequences composed of up to 25 residues of the same handedness in the polymerization of racemic valine or leucine N-carboxyanhydrides in aqueous solutions, as initiated by amines. The composition of the oligopeptides was determined by MALDI-TOF mass spectrometry, and the sequences of some of the heterochiral diastereoisomers were studied by MALDI-TOF MS/MS performed on samples in which the S enantiomers of the monomer were tagged with deuterium atoms. The process comprises several steps: 1) a Markov mechanism of asymmetric induction in the early stages of the polymerization yields libraries of racemic oligopeptides enriched with isotactic diastereoisomers, together with oligopeptide sequences containing enantiomeric blocks of homochiral residues; 2) the short peptides self-assemble into racemic colloidal architectures that serve as regio-enantioselective templates in the ensuing process of chain elongation; 3) homochiral residues of the amino acids located at the periphery of these colloidal aggregates exert efficient enantioselection, which results in the formation of long isotactic oligopeptides. The final diastereoisomeric distribution of the peptides depends upon the composition of the templates, which is determined by the concentration of the initiator. The racemic mixtures of isotactic peptides can be desymmetrized by using enantiopure methyl esters of alpha-amino acids as initiators.     

Amphiphilic Homochiral Oligopeptides Generated via Phase Separation of Nonracemic α‐Amino Acid Derivatives and Lattice‐Controlled Polycondensation in a Phospholipid Environment

Racemic S‐ethyl thioesters of N^ε‐stearoyllysine (= S‐ethyl (R,S)‐2‐amino‐6‐(stearoylamino)hexanethioate) and S‐ethyl thioesters of γ‐stearyl glutamic acid (=stearyl (R,S)‐4‐amino‐5‐(ethylsulfanyl)‐5‐oxopentanoate) self‐assemble as separated two‐dimensional crystalline monolayers within an achiral phospholipid environment of racemic 1,2‐dipalmitoylglycerol (DPG) and 1,2‐dipalmitoylglycero‐3‐phosphoethanolamine (DPPE), as demonstrated by grazing‐incidence X‐ray‐diffraction (GIXD) measurements performed on the surface of H₂O. Lattice‐controlled polycondensation within these crystallites with deuterium‐enantiolabeled monomers was initiated by injecting aqueous solutions of Ag⁺ or I₂/KI beneath the monolayers, which yielded mixtures of diastereoisomeric oligopeptides containing up to six to eight repeating units, as analyzed by MALDI‐TOF mass spectrometry. Analysis of the diastereoisomeric distribution showed an enhanced relative abundance of the oligopeptides with homochiral sequences containing three or more repeating units. Within the DPPE monolayers, the nucleophilic amino group of the phospholipid operates as an initiator of polymerization at the periphery of the monomer two‐dimensional crystallites. Enhanced relative abundance of enantiomerically enriched homochiral oligopeptides was obtained by the polycondensation of nonracemic monomers. This enhancement indicated a phase separation into racemic and enantiomorphous monomer crystallites within the phospholipid environment, although this separation could not be observed directly by GIXD. A possible role that might have been played by crystalline assemblies for the abiotic generation and amplification of oligopeptides with homochiral sequences is discussed.     

Structures formed by the chiral assembly of racemic mixtures of enantiomers: iodination products of elaidic and oleic acids

The self-assembled monolayer structure of the products of elaidic acid iodination (the racemic mixture of 9,10-(9S,10R)-diiodooctadecanoic acid and 9,10-(9R,10S)-diiodooctadecanoic acid) and the products of oleic acid iodination (the racemic mixture of 9,10-(9R,10R)-diiodooctadecanoic acid and 9,10-(9S,10S)-diiodooctadecanoic acid) are studied by high-resolution scanning tunneling microscopy. For the iodination products of elaidic acid, the separation of enantiomers into distinct chiral domains during the formation of the 2-D crystal on the highly ordered pyrolytic graphite (HOPG) surface is not observed. Instead, within the diiodooctadecanoic acid SAM, each row of molecules is composed of opposite racemates. The two opposite racemates pack alternately inside a row, using different faces to adsorb on the surface. The unit cell is composed of a pair of opposite racemates, forming a heterochiral structure. For the iodination products of oleic acid, the racemic mixture is observed to exhibit quasi-phase separation during the formation of the 2-D crystal on the HOPG surface. Each row is composed of homochiral acid molecules, either the 9,10-(9R,10R)-diiodooctadecanoic acid (R) or the 9,10-(9S,10S)-diiodooctadecanoic acid (S). The R row and the S row pack alternately, with a unit cell composed of four molecules. Two of the molecules in the unit cell are the 9,10-(9R,10R)-diiodooctadecanoic acid (R) molecules; two are the 9,10-(9S,10S)-diiodooctadecanoic acid (S) molecules. In the unit cell, the two molecules that have the same chirality pack antiparallel inside the homochiral row, using different faces to adsorb on the surface. These results suggest that several different types of chiral assembly are possible. Enantiomers with opposite chirality exhibit many chiral assembly patterns, forming heterochiral structures on the surface in addition to separation to form macroscopic chiral domains. By using different conformations, similar enantiomers with opposite chirality will display many chiral assembly patterns to form heterochiral structures on the surface.     

Properties of β-sitostanol/DPPC monolayers studied with Grazing Incidence X-ray Diffraction (GIXD) and Brewster Angle Microscopy

Although the influence of structurally modified sterols on artificial membranes has been intensively investigated, studies on the properties of stanols, which are saturated analogs of sterols, are very rare. Therefore, we have performed Grazing Incidence X-ray Diffraction (GIXD) experiments aimed at studying in-plane organization of a plant stanol-β-sitostanol monolayer and its mixtures with 1,2-dipalmitoyl-sn-glycero-3-phosphocholine - DPPC at the air/water interface. The collected GIXD data, resulting in-plane parameters and BAM images provide information on molecular organization and in-plane ordering of the investigated films. It was found that the lateral organization of β-sitostanol/DPPC monolayers depends on their composition. The oblique structure of the in-plane lattice of tilted hydrophobic region of molecules, found for DPPC film, is maintained at 10 mol% of stanol in the system. However, at 30 and 90 mol% of stanol in the mixture, the arrangement of molecules is hexagonal and they are oriented perpendicularly to the interface. With the addition of stanol the extend of the in-plane order of the monolayers decreases. Moreover, in mixtures the ordered domains consist of both monolayer's components. Additionally, β-sitostanol film is of similar in-plane organization as the corresponding sterol monolayer (β-sitosterol) and stanol induces condensing effect on DPPC.     

Homochiral oligopeptides via a lattice-controlled polymerisation in racemic crystals of valine N-carboxyanhydride suspended in aqueous solutions

As part of our program on the biochirogenesis of homochiral peptides, we report the formation of racemic parallel (p) beta sheets composed of alternating R and S chains of up to 14-15 repeat units of the same handedness through the polymerisation of (R,S)-valine N-carboxyanhydride (NCA) crystals suspended in aqueous solutions of a primary amine as the initiator. The occurrence of such a lattice-controlled reaction accompanied by a reduction in volume implies the operation of a mechanism that differs from that of the common solid-state polymerisation in vinyl systems. The topotacticity of the reaction is explained through the operation of a multistep nonlinear process comprising lattice control coupled with an asymmetric induction in the formation of homochiral short peptides followed by their self-assembly into racemic p beta sheets, which operate as efficient templates in the ensuing process of enantioselective chain elongation at the polymer/crystal interface. The composition of the diastereoisomeric libraries of oligopeptides was determined by MALDI-TOF and MALDI-TOF-TOF MS analyses of the products obtained from monomers enantioselectively labelled with deuterium. The structure of the p beta sheets could be determined by initiating the polymerisation reaction with water-soluble esters of enantiopure alpha-amino acids or short peptides. The same reaction performed with the monomer crystals suspended in hexane yielded a complex mixture of diastereoisomeric oligopeptides, thus highlighting the indispensable role played by water in controlling the stereoselectivity of the reaction. By contrast, polymerisation of (R,S)-leucine NCA crystals, with a different packing arrangement that presumably does not endorse the formation of periodic peptide templates, yielded, both in aqueous and hexane suspensions, libraries of peptides dominated by heterochiral diastereoisomers.     

Crystalline Phase Separation of Racemic and Nonracemic Zwitterionic α‐Amino Acid Amphiphiles in a Phospholipid Environment at the Air/Water Interface: A Grazing‐Incidence X‐Ray Diffraction Study

A grazing‐incidence X‐ray‐diffraction (GIXD) study of the self‐assembly, on water, of nonracemic γ‐stearyl glutamic acid (pure or as a mixture with racemic or (S)‐1,2‐dipalmitoyl‐glycero‐3‐phosphoethanolamine (DPPE)) demonstrated a phase separation of the α‐amino acid amphiphile into racemic and enantiomorphous two‐dimensional crystallites within the phospholipid domains. The packing arrangements of the two α‐amino acid crystalline phases were identical to those found in the absence of DPPE and have been determined, at almost atomic resolution, by X‐ray structure‐factor calculations. By contrast, racemic and nonracemic N^ε‐stearoyllysine spontaneously segregated into two‐dimensional enantiomorphous domains within the DPPE environment that induced a change in the tilt direction of the hydrocarbon chains of the α‐amino acid molecules. Phase separation of nonracemic amphiphiles, originating from preferred lateral homochiral or heterochiral intermolecular interactions, is in agreement with the formation of enantiomerically pure or enriched homochiral oligopeptides in overrepresented amounts in the polycondensation of activated nonracemic amphiphilic α‐amino acids on plain water or within phospholipid monolayers.     

Homochiral oligopeptides generated via an asymmetric induction in racemic 2D crystallites at the air-water interface; the system ethyl/thio-ethyl esters of long-chain amphiphilic alpha-amino acids

N(epsilon)-stearoyl-lysine-ethyl-ester (C18-OE-Lys) operates as an efficient desymmetrizing agent for the generation of homochiral oligopeptides via a reaction catalyzed by silver ions in two-dimensional (2D) quasi-racemic crystallites of the corresponding thio-ester (C18-TE-Lys) self-assembled on water.     

Elasticity of crystalline beta-sheet monolayers

Designed amphiphilic beta-sheet peptides with the sequence Pro-Glu-(Phe-Glu)(n)-Pro (n = 2-7) were previously shown by grazing incidence X-ray diffraction (GIXD), to form ordered two-dimensional (2-D) monolayer structures at interfaces induced by the proline residues at peptide termini. The GIXD diffraction pattern was modeled with two coexisting lattice arrangements, suggesting structural flexibility exhibited in the multiple ways by which beta-strands and their amino acid side chains pack into ordered 2-D structures. Here, we find by in-situ GIXD measurements that the ordered beta-sheet assemblies may undergo a quasi-reversible compression and expansion cycle at the air-water interface. The diffraction measurements indicate that on compression the repeat distance that corresponds to the long axes of the peptide strands may decrease by up to 37% in length. Upon expansion the compressed beta-sheet assemblies revert elastically to their original conformation. The interstrand repeat distance along the peptide hydrogen bonds apparently does not change along the film compression and expansion. Based on the GIXD data, at surface pressures higher than approximately 3 mN/m, beyond the peptide limiting area per molecule, the compressibility is 7.4 +/- 0.6 m/N. The out-of-plane Bragg rod diffraction patterns imply that in the compressed state the beta-strands buckle up in reaction to the increase in surface pressure. At low surface pressure, the 2-D compressibility of the crystalline beta-sheet was estimated at approximately 32 m/N attributed to interdomain rearrangements.     

Enantiospecific adsorption of cysteine at chiral kink sites on Au(110)-(1 x 2)

Enantiospecific adsorption of cysteine molecules onto chiral kink sites on the Au(110)-(1x2) surface was observed by scanning tunneling microscopy. l- and d-cysteine dimers were found to adopt distinctly different adsorption geometries at S kinks, which can be understood from the need to reach specific, optimum molecule-substrate interaction points. Extended, homochiral domains of l/d-cysteine were furthermore observed to grow preferentially from R/S kinks. The results constitute the first direct, microscopic observation of enantiospecific molecular interaction with chiral sites on a metal single-crystal surface.     

Tailoring homochirality at surfaces: going beyond molecular handedness

Chirality can be bestowed upon a surface by the adsorption of molecules and is usually discussed in terms of the molecular handedness. However, the adsorption process often leads to a new manifestation of chirality in the form of the adsorption footprint, which can also be chiral and generate mirror-images in 2-D. Therefore, in describing the chirality of the interface, one must consider both the handedness and the adsorption 'footedness' of the system. Specifically, the creation of a truly homochiral surface must ensure that a single chirality is expressed for each aspect, and requires not only the control of molecule handedness but also direct control over footedness. Here, we demonstrate the ability to engineer homochiral footedness by a structural modification of enantiopure (S)-proline, which normally creates a (4 × 2) organization on a Cu(110) surface with heterochiral footedness. This modification of proline via the addition of a double bond within the pyrrolidine ring, yielding 3-pyrroline-2-carboxylic acid (PCA), is sufficient to drive the footprints of the entire (4 × 2) assembly from heterochiral to homochiral, leading to the creation of a truly homochiral interface The effects of modifications upon the footprint arrangements were characterized at the single-molecule level by scanning tunnelling microscopy, reflection absorption infrared spectroscopy and periodic density functional theory calculations. The control of adsorption footprints is not only pivotal to tailoring chirality at surfaces but also plays a key role in dictating the organization, the outward facing functionalities and the response of the organic-inorganic interface.     

Chiral Amplification of Oligopeptides in the Polymerization of α‐Amino Acid N‐Carboxyanhydrides in Water

This article is concerned with the chiral amplification of oligopeptides formed in the polymerization of chiral, nonracemic mixtures of the N‐carboxyanhydride (NCA) of Leu and Glu in aqueous solution. Labeling (deuteration) of one enantiomer and reversed‐phase and normal‐phase high‐performance liquid chromatography mass spectrometry (RP‐ and NP‐HPLC/MS, respectively) were used to determine the product distribution, both with respect to oligopeptide chain length and stereoisomer distribution. Starting the polymerization with an enantiomeric excess (ee) of 20% of the L ‐enantiomer (L ‐amino acid/D ‐amino acid 6 : 4) leads to an ee of 73% at the level of the homochiral enantiomeric (Leu)₅, and of 71% at the level of the homochiral enantiomeric (Glu)₇. For the Leu system and in the presence of a solid support (quartz), the ee reached values of up to 100%. We argue that such amplification processes could be relevant for the chemical evolution towards single‐handedness.     

Chiral discrimination of a gemini-type surfactant with rigid spacer at the air-water interface

Spontaneous separation of chiral phases was observed in the monolayers of a racemate of gemini-type twin-tailed, twin-chiral amphiphiles, (2R,3R)-(+)-bis(decyloxy)succinic acid and (2S,3S)-(-)-bis(decyloxy)succinic acid. The pressure-area isotherms of the interfacial monolayers formed at the liquid-air interface, and the 2D lattice structures studied through surface probe measurements revealed that the racemate exhibits a homochiral discrimination of the enantiomers in two dimensions. An enantiomeric excess (e,e) of 20% was sufficient to break the chiral symmetry at the air-water interface for a homochiral interaction. Langmuir monolayers on ZnCl2 and CaCl2 subphases manifested chiral discrimination with Zn2+ evidencing homochiral interaction with a chelate-type complex, whereas Ca2+ resulted in a heterochiral interaction forming an ionic-type complex. For the chiral asymmetric units, oblique and rectangular unit cells of the racemic monolayer had exclusive requirements of homo- and heterochiral recognitions for Zn2+ and Ca2+ ions, respectively. Monolayers transferred from the condensed phase at 25 mN/m onto hydrophilic Si(100) and quartz substrates revealed the formation of bilayers through transfer-induced monolayer buckling. The emergence of homochiral discrimination was explained using the effective-pair-potential (EPP) approach.     

基于半刚性乳酸衍生物的单一手性配位聚合物的合成、 结构与性质

在溶剂热反应条件下, 用预先合成的乳酸衍生物(R)-H₂CBA和(S)-H₂CBA分别与含氮辅助配体(E)-1,2-二(4-吡啶基)乙烯(DPEE)和1,4-二(1H-咪唑-1-基)苯(1,4-DIB)组合, 制备出2对不同结构的单一手性配位聚合物[Cd₂((R)-CBA)₂(DPEE)(H₂O)₂]_n(1-D), [Cd₂((S)- CBA)₂(DPEE)(H₂O)₂]_n(1-L), [Cd((R)-CBA)(1,4-DIB)]·H₂O(2-D)和[Cd((S)-CBA)(1,4-DIB)]·H₂O(2-L). 其中1-D和1-L是由梯形Cd-CBA链和DPEE配体连接成的二维框架结构; 而2-D和2-L是三维超分子框架结构, 包含3种不同类型的对映手性螺旋链. 对上述化合物进行了粉末X射线衍射、 热重分析和圆二色谱分析, 并对其荧光性质进行了讨论.     

Hydrogen-bonded monolayers and interdigitated multilayers at the air-water interface

Crystalline monolayers of octadecylsulfonate amphiphiles (C18S) separated by hydrophilic guanidinium (G) spacer molecules were formed at the air-water interface at a surface coverage that was consistent with that expected for a fully condensed monolayer self-assembled by hydrogen bonding between the G ions and the sulfonate groups. The surface pressure-area isotherms reflected reinforcement of this monolayer by hydrogen bonding between the G ions and the sulfonate groups, and grazing incidence X-ray diffraction (GIXD) measurements, performed in-situ at the air-water interface, revealed substantial tilt of the alkyl hydrophobes (t = 49 degrees with respect to the surface normal), which allowed the close packing of the C18 chains needed for a stable crystalline monolayer. This property contrasts with behavior observed previously for monolayers of hexadecylbiphenylsulfonate (C16BPS) and G, which only formed crystallites upon compression, accompanied by ejection of the G ions from the air-water interface. Upon compression to higher surface pressures, GIXD revealed that the highly tilted (G)C18S monolayer crystallites transformed to a self-interdigitated (G)C18S crystalline multilayer accompanied by a new crystalline monolayer phase with slightly tilted alkyl chains and disordered sulfonate headgroups. This transformation was dependent on the rate of compression, suggesting kinetic limitations for the "zipper-like" transformation from the crystalline monolayer to the self-interdigitated (G)C18S crystalline multilayer.     

Structure and phase behavior of archaeal lipid monolayers

We report X-ray reflectivity (XRR) and grazing incidence X-ray diffraction (GIXD) measurements of archaeal bipolar tetraether lipid monolayers at the air-water interface. Specifically, Langmuir films made of the polar lipid fraction E (PLFE) isolated from the thermoacidophilic archaeon Sulfolobus acidocaldarius grown at three different temperatures, i.e., 68, 76, and 81 °C, were examined. The dependence of the structure and packing properties of PLFE monolayers on surface pressure were analyzed in a temperature range between 10 and 50 °C at different pH values. Additionally, the interaction of PLFE monolayers (using lipids derived from cells grown at 76 °C) with the ion channel peptide gramicidin was investigated as a function of surface pressure. A total monolayer thickness of approximately 30 ? was found for all monolayers, hinting at a U-shaped conformation of the molecules with both head groups in contact with the interface. The monolayer thickness increased with rising film pressure and decreased with increasing temperature. At 10 and 20 °C, large, highly crystalline domains were observed by GIXD, whereas at higher temperatures no distinct crystallinity could be observed. For lipids derived from cells grown at higher temperatures, a slightly more rigid structure in the lipid dibiphytanyl chains was observed. A change in the pH of the subphase had an influence only on the structure of the lipid head groups. The addition of gramicidin to an PLFE monolayer led to a more disordered state as observed by XRR. In GIXD measurements, no major changes in lateral organization could be observed, except for a decrease of the size of crystalline domains, indicating that gramicidin resides mainly in the disordered areas of the monolayer and causes local membrane perturbation, only.     

Unexpected stability of phospholipid langmuir monolayers deposited on Triton X-100 aqueous solutions

We studied at the molecular level the interaction between neutral detergent Triton X-100 aqueous solution and a phospholipid Langmuir monolayer deposited on top using surface pressure measurement and grazing incidence X-ray diffraction (GIXD). Macroscopically, the detergent-phospholipid system follows the Gibbs law. However, GIXD shows that the detergent and the phospholipid segregate at the interface. The molecular organization of pure phospholipid domains is imposed by the detergent through surface pressure. Compression and expansion of the surface monolayer system in its final state reveal the stability of the phospholipids domains against dissolution by the detergent in the subphase, even above the detergent cmc. This resistance to dissolution is suppressed by an expansion of the monolayer.     

Planar chiral dianthranilide and dithiodianthranilide molecules: optical resolution, chiroptical spectra, and molecular self-assembly

Planar chiral dianthranilide (1) was resolved to enantiomers with use of (-)-(1S,4R)-camphanoyl chloride as a chiral derivatizing agent. The (+)-1 enantiomer was assigned the S absolute configuration from the X-ray crystal structure of its N,N'-dicamphanoyl derivative. Optical resolution of dithionodianthranilide (2) was accomplished by inclusion crystallization with (R,R)-1,2-diaminocyclohexane, and the X-ray structure of the corresponding adduct revealed the (-)-2stereoisomer has the R configuration. A slow boat-to-boat ring inversion (DeltaG(++) = 24.1 +/- 0.1 kcal mol(-1)) causes racemization of (+)-1 in solution as manifested by a gradual decrease of the CD spectrum whereas, (-)-2 is configurationally stable at these conditions. The analysis of the CD spectra of the title compounds showed that the n-pi* Cotton effect signs are determined by the helicity of the skewed benzamide and thiobenzamide chromophores. The solid-state structures of the racemic and homochiral forms of 1 and 2 show different self-assembly patterns: the racemate (+/-)-1 prefers the cyclic R(2)(2)(8) hydrogen bond motif, whereas the crystalline DMSO solvates of (+/-)-1 and (+)-1 consist of 1D homochiral hydrogen-bonded assemblies generated by the C(6) motif. In the case of dithionolactams (+/-)-2 and (-)-2 two types of 1D networks were observed: in the racemate they are generated by the centrosymmetric R(2)(2)(8) and R(2)(2)(12) hydrogen bond motifs, whereas the molecules in the homochiral crystals are connected solely with use of the strongly nonplanar R(2)(2)(8) motif.