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

Abstract

Dedicated to Professor Duilio Arigoni on the occasion of his 75th birthday A grazing-incidence X-ray-diffraction (GIXD) study of the self-assembly, on water, of nonracemic gstearyl glutamic acid (pure or as a mixture with racemic or (S)-1,2-dipalmitoyl-glycero-3-phosphoethanolamine (DPPE)) demonstrated a phase separation of the a-amino acid amphiphile into racemic and enantiomorphous two-dimensional crystallites within the phospholipid domains. The packing arrangements of the two a-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 estearoyllysine 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 a-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 aamino acids on plain water or within phospholipid monolayers.Introduction. ± As a part of our studies on the formation of homochiral oligopeptides from nonracemic activated a-amino acid monomers, we have proposed a general mechanism for the amplification of chirality that encompasses a phase separation of the nonracemic monomers into two-dimensional (2D) crystallites, either on H 2 O or within a membrane-like environment of a phospholipid monolayer, followed by a lattice-controlled polymerization. In the preceding article of this journal issue [1], we demonstrated that polycondensation of nonracemic S-ethyl thioesters of both lysine and glutamic acid amphiphiles gives rise to homochiral oligopeptides, when embedded within a phospholipid monolayer, as determined by MALDI-TOF MS of deuteriumenantiolabeled monomers. Grazing-incidence X-ray-diffraction (GIXD) studies of the films composed of an equimolar mixture of racemic phospholipids with racemic thioesters clearly showed a phase separation between 2D crystalline domains of phospholipid and those of the thioesters, very similar to those observed for the pure components. However, it was not possible for these systems to demonstrate, by direct GIXD measurement, the occurrence of a phase separation of the nonracemic thioesters into a mixture of racemic and enantiomorphous domains. This was due to either similar X-ray diffraction patterns or an induced line-epitaxial crystallization of the enantiomorphous crystalline phase alongside the racemic crystallites, as discussed elsewhere [2].

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

“…For the C 18 -TE-Lys system, a possible line-epitaxial crystallization of (S)-C 18 -TE-Lys alongside the racemic crystallites was proposed [19]. However, phase separation of nonracemic amphiphilic a-amino acids within phospholipids is feasible and was detected by GIXD for an appropriate system (see the following article in this issue [26]). The formation of oligopeptides covalently linked to a DPPE molecule indicates that the polycondensation reaction, catalyzed by Ag ions, started at the grain-boundaries between DPPE crystallites and those of the racemic or enantiomorphous amino acid monomers.…”

Challenges and breakthroughs in recent research on self-assembly

“…The air-water interface has been also used for chiral recognition within membrane components [695][696][697][698][699][700] and/or between amphiphile and aqueous guests [701][702][703][704][705][706][707][708]. Mechanical control of chiral recognition was recently achieved using the novel concept of molecular twisting, as shown in figure 79A, where an octacoordinate sodium complex of a polycholesteryl-substituted cyclen embedded at the air-water interface was used as a molecular host [709].…”

“Absolute” Asymmetric Polymerization within Crystalline Architectures: Relevance to the Origin of Homochirality

“…A polymerization reaction within these crystallites takes place, along the glide plane, between the heterochiral The results of GIXD studies of the packing arrangement of nonracemic amphiphilic α-amino acids have shown that the latter undergo separation, either on pure water or within a monolayer of phospholipids, into a mixture of racemic and enantiomorphous domains [25,32]. Polymerization then takes place within each of the two types of crystallites, yielding syndiotactic peptides in the racemic crystallites and homochiral peptides within the enantiomorphous domains.…”