Louis A. Cuccia

Naphthyridine-Based Helical Foldamers and Macrocycles: Synthesis, Cation Binding, and Supramolecular Assemblies

Unraveling the factors that control the conformation of molecular chains is of great interest both for understanding the shape of biological molecular strands and for designing artificial ones that adopt desired forms. Thus, a variety of artificial folding codons have been identified that enforce the formation, among others, of helices, strands, and loops, the major emphasis being on the shape of the foldamer. We report herein the synthesis and study of a family of foldamers and macrocycles based on the 1,8-naphthyridine and pyrimidine units, whose internal cavity is large enough to accommodate ionic substrates, and focus on the impact of guest binding within a cylindrical environment. Interestingly, the binding event within these large oligomers is translated to the outside of the receptors and affects the interaction of the overall complexes with the outside world. For instance, alkali cations bind to the one-turn helices and macrocycles to promote fibril formation and aggregation. Also, polyammonium substrates are able to tune the length of the overall helix assemblies and the rigidity of long oligomers. The reported data on one-turn, two-turn helices and macrocycles not only allows one to devise a model for the ion-controlled supramolecular assembly of such systems but also provides evidence that such controlled scaffolds bear promise in the design of complex systems.

Complete asymmetric amplification of ethylenediammonium sulfate using an abrasion/grinding technique

Complete asymmetric amplification of ethylenediammonium sulfate was achieved under continuous dissolution/crystallization conditions using an abrasion/grinding method.

Single molecule atomic force microscopy and force spectroscopy of chitosan

Atomic force microscopy (AFM) and AFM-based force spectroscopy was used to study the desorption of individual chitosan polymer chains from substrates with varying chemical composition. AFM images of chitosan adsorbed onto a flat mica substrate show elongated single strands or aggregated bundles. The aggregated state of the polymer is consistent with the high level of flexibility and mobility expected for a highly positively charged polymer strand. Conversely, the visualization of elongated strands indicated the presence of stabilizing interactions with the substrate. Surfaces with varying chemical composition (glass, self-assembled monolayer of mercaptoundecanoic acid/decanethiol and polytetrafluoroethylene (PTFE)) were probed with chitosan modified AFM tips and the corresponding desorption energies, calculated from plateau-like features, were attributed to the desorption of individual polymer strands. Desorption energies of 2.0±0.3×10(-20)J, 1.8±0.3×10(-20)J and 3.5±0.3×10(-20)J were obtained for glass, SAM of mercaptoundecanoic/dodecanethiol and PTFE, respectively. These single molecule level results can be used as a basis for investigating chitosan and chitosan-based materials for biomaterial applications.

Design and Synthesis of Urea-Linked Aromatic Oligomers—A Route Towards Convoluted Foldamers

Herein we report the design and synthesis of crescent-shaped and helical urea-based foldamers, the curvature of which is controlled by varying the constituent building blocks and their connectivity. These oligomers are comprised of two, three or five alternating aromatic heterocycles (pyridazine, pyrimidine or pyrazine) and methyl-substituted aromatic carbocycles (tolyl, o-xylyl or m-xylyl) connected together through urea linkages. A crescent-shaped conformational preference is encoded within these pi-conjugated urea-linked oligomers based on intramolecular hydrogen bonding and steric interactions; the degree of curvature is tuned by the urea connectivity to the heterocycles and the aryl groups. NMR characterization of these foldamers confirms the intramolecular hydrogen-bonded conformation expected (Z,E configuration of the urea bond) in both the pyridazyl and pyrimidyl foldamers in solution. An X-ray crystal structure of the N(3),N(6)-diisobutylpyridazine-4,6-diamine-o-tolyl urea-linked foldamer (4) confirms the presence of N-H...N hydrogen bonds between the heterocyclic nitrogen atom and the free hydrogen of the urea linkage. Additionally, the tolyl methyl group interacts unfavourably with the urea carbonyl oxygen, thus destabilising the alternate planar conformation.

Amino acid directed mirror symmetry breaking and chiral amplification of ethylenediammonium sulfate crystals

Directed chiral symmetry breaking and asymmetric amplification of ethylenediammonium sulfate in the presence of chiral amino acids was achieved using an abrasion/grinding method.

Rapid and facile solvent-free mechanosynthesis in a cell lysis mill: preparation and mechanochemical complexation of aminobenzoquinones

A cell lysis mill, typically used for the breakdown of biological structures in microbiological and biochemical studies, was used as a tool for rapid, solvent-free and general synthesis of short- and long-chain substituted zwitterionic meta- and para-aminobenzoquinones, never previously prepared under solvent-free conditions. Rapid agitation and self-heating in the lysis mill enabled thermally-demanding reactions without external solvent, providing yields comparable to those obtained by conventional solution chemistry, ball milling and melt chemistry. The lysis mill is also suitable for coordination-based reactions, demonstrated by the mechanosynthesis of a mononuclear Ni(II) meta-benzoquinonemonoimine complex.

Imaging the selective binding of synapsin to anionic membrane domains.

Synapsins are membrane‐associated proteins that cover the surface of synaptic vesicles and are responsible for maintaining a pool of neurotransmitter‐loaded vesicles for use during neuronal activity. We have used atomic force microscopy (AFM) to study the interaction of synapsin I with negatively charged lipid domains in phase‐separated supported lipid bilayers prepared from mixtures of phosphatidylcholines (PCs) and phosphatidylserines (PSs). The results indicate a mixture of electrostatic binding to anionic PS‐rich domains as well as some nonspecific binding to the PC phase. Interestingly, both protein binding and scanning with synapsin‐coated AFM tips can be used to visualize charged lipid domains that cannot be detected by topography alone.

Perfluorophenyl azide immobilization chemistry for single molecule force spectroscopy of the concanavalin A/mannose interaction.

The versatility of perfluorophenyl azide (PFPA) derivatives makes them useful for attaching a wide variety of biomolecules and polymers to surfaces. Herein, a single molecule force spectroscopy (SMFS) study of the concanavalin A/mannose interaction was carried out using PFPA immobilization chemistry. SMFS of the concanavalin A/mannose interaction yielded an average unbinding force of 70-80 pN for loading rates between 8000 and 40,000 pN/s for mannose surfaces on aminated glass, and an unbinding force of 57 ± 20 pN at 6960 pN/s for mannose surfaces on gold-coated glass. Dynamic force spectroscopy was used to determine the dissociation rate constant, k(off), for this interaction to be 0.16 s(-1).

Oriented attachment by enantioselective facet recognition in millimeter-sized gypsum crystals

Crystal growth by oriented attachment involves the spontaneous self-assembly of adjoining crystals with common crystallographic orientations. Herein, we report the oriented attachment of gypsum crystals on agitation to form stereoselective mesoscale aggregates.

Homochiral crystal generation via sequential dehydration and Viedma ripening

1,2-Bis(N-benzoyl-N-methylamino)benzene (2) forms centrosymmetric hydrate crystals (2·xH2O) and non-centrosymmetric anhydrous crystals. Dehydration of this hydrate (30 min at 140 °C) resulted in the formation of chiral crystals (i.e. a physical racemate of the conglomerate crystals) as verified using solid-state circular dichroism and powder X-ray diffraction. Subsequent attrition-enhanced deracemization, also known as Viedma ripening, was used to obtain homochiral crystals of 2 within 5 h.