Peptide-Directed Supramolecular Self-Assembly of N-Substituted Perylene Imides

<p>Synthetic peptides offer enormous potential to encode the assembly of molecular electronic components, provided that the complex range of interactions is distilled into simple design rules. Herein is reported a spectroscopic investigation of aggregation in an extensive series of peptide-perylene imide conjugates designed to interrogate the effect of structural variations. Throughout the course of this study, the self-assembly and photophysical properties of the compounds are explored to better understand the behavior and application of these materials. Three principal avenues of inquiry are applied: (1) the evaluation of structure-property relationships from a thermodynamic perspective, (2) the examination of peptide chiral effects upon properties and self-assembly, and (3) an application of the understanding gained from rationally designed systems to effectively utilize naturally optimized peptides in bio-organic electronics. By fitting different contributions to temperature-dependent optical absorption spectra, this study quantifies both the thermodynamics and the nature of aggregation for peptides with incrementally varying hydrophobicity, charge density, length, amphiphilic substitution with a hexyl chain, and stereocenter inversion. Coarse effects like hydrophobicity and hexyl substitution are seen to have the greatest impact on binding thermodynamics, which are evaluated separately as enthalpic and entropic contributions. Moreover, significant peptide packing effects are resolved via stereocenter inversion studies, particularly when examining the nature of aggregates formed and the coupling between π-electronic orbitals. Peptide chirality overall is seen to influence the self-assembly of the perylene imide cores into chiral nanofibers, and peptide stereogenic positions, stereochemical configurations, amphiphilic substitution, and perylene core modification are evaluated with respect to chiral assembly. Stereocenters in peptide residue positions proximal to the perylene core (1-5 units) are seen to impart helical chirality to the perylene core, while stereocenters in more distal residue positions do not exert a chiral influence. Diastereomers involving stereocenter inversions within the proximal residues consequently manifest spectroscopically as pseudo-enantiomers. Increased side-chain steric demand in the proximal positions gives a similar chiral influence but exhibits diminished Cotton Effect intensity with additional longer wavelength features attributed to interchain excimers. Amphiphilic substitution of a peptide with an alkyl chain disrupts chiral self-assembly, while an amphiphilic structure achieved through the modification of the perylene imide core with a bisester moiety prompts strongly exciton-coupled, chiral, solvent-responsive self-assembly into long nanofilaments. Informed by rationally designed sequences, and capitalizing upon the optimization seen in many natural systems, specific peptide sequences designed by inspection of protein-protein interfaces have been identified and used as tectons in hybrid functional materials. An 8-mer peptide derived from an interface of the peroxiredoxin family of self-assembling proteins is exploited to encode the assembly of perylene imide-based organic semiconductor building blocks. By augmenting the peptide with additional functionality to trigger aggregation and manipulate the directionality of peptide-semiconductor coupling, a series of hybrid materials based on the natural peptide interface is presented. Using spectroscopic probes, the mode of self-assembly and the electronic coupling between neighboring perylene units is shown to be strongly affected by the number of peptides attached, and by their backbone directionality. The disubstituted material with peptides extending in the N-C direction away from the perylene core exhibits strong coupling and long-range order, which are both attractive properties for electronic device applications. A bio-organic field-effect transistor is fabricated using this material, highlighting the possibilities of exploiting natural peptide tectons to encode self-assembly in other functional materials and devices. These results advance the development of a quantitative framework for establishing structure-function relationships that will underpin the design of self-assembling peptide electronic materials. The results further advance a model for adapting natural peptide sequences resident in β-continuous interfaces as tectons for bio-organic electronics.</p>

Peptide-Directed Supramolecular Self-Assembly of N-Substituted Perylene Imides

<p>Synthetic peptides offer enormous potential to encode the assembly of molecular electronic components, provided that the complex range of interactions is distilled into simple design rules. Herein is reported a spectroscopic investigation of aggregation in an extensive series of peptide-perylene imide conjugates designed to interrogate the effect of structural variations. Throughout the course of this study, the self-assembly and photophysical properties of the compounds are explored to better understand the behavior and application of these materials. Three principal avenues of inquiry are applied: (1) the evaluation of structure-property relationships from a thermodynamic perspective, (2) the examination of peptide chiral effects upon properties and self-assembly, and (3) an application of the understanding gained from rationally designed systems to effectively utilize naturally optimized peptides in bio-organic electronics. By fitting different contributions to temperature-dependent optical absorption spectra, this study quantifies both the thermodynamics and the nature of aggregation for peptides with incrementally varying hydrophobicity, charge density, length, amphiphilic substitution with a hexyl chain, and stereocenter inversion. Coarse effects like hydrophobicity and hexyl substitution are seen to have the greatest impact on binding thermodynamics, which are evaluated separately as enthalpic and entropic contributions. Moreover, significant peptide packing effects are resolved via stereocenter inversion studies, particularly when examining the nature of aggregates formed and the coupling between π-electronic orbitals. Peptide chirality overall is seen to influence the self-assembly of the perylene imide cores into chiral nanofibers, and peptide stereogenic positions, stereochemical configurations, amphiphilic substitution, and perylene core modification are evaluated with respect to chiral assembly. Stereocenters in peptide residue positions proximal to the perylene core (1-5 units) are seen to impart helical chirality to the perylene core, while stereocenters in more distal residue positions do not exert a chiral influence. Diastereomers involving stereocenter inversions within the proximal residues consequently manifest spectroscopically as pseudo-enantiomers. Increased side-chain steric demand in the proximal positions gives a similar chiral influence but exhibits diminished Cotton Effect intensity with additional longer wavelength features attributed to interchain excimers. Amphiphilic substitution of a peptide with an alkyl chain disrupts chiral self-assembly, while an amphiphilic structure achieved through the modification of the perylene imide core with a bisester moiety prompts strongly exciton-coupled, chiral, solvent-responsive self-assembly into long nanofilaments. Informed by rationally designed sequences, and capitalizing upon the optimization seen in many natural systems, specific peptide sequences designed by inspection of protein-protein interfaces have been identified and used as tectons in hybrid functional materials. An 8-mer peptide derived from an interface of the peroxiredoxin family of self-assembling proteins is exploited to encode the assembly of perylene imide-based organic semiconductor building blocks. By augmenting the peptide with additional functionality to trigger aggregation and manipulate the directionality of peptide-semiconductor coupling, a series of hybrid materials based on the natural peptide interface is presented. Using spectroscopic probes, the mode of self-assembly and the electronic coupling between neighboring perylene units is shown to be strongly affected by the number of peptides attached, and by their backbone directionality. The disubstituted material with peptides extending in the N-C direction away from the perylene core exhibits strong coupling and long-range order, which are both attractive properties for electronic device applications. A bio-organic field-effect transistor is fabricated using this material, highlighting the possibilities of exploiting natural peptide tectons to encode self-assembly in other functional materials and devices. These results advance the development of a quantitative framework for establishing structure-function relationships that will underpin the design of self-assembling peptide electronic materials. The results further advance a model for adapting natural peptide sequences resident in β-continuous interfaces as tectons for bio-organic electronics.</p>

N-tert-Butyl-2-{2-[2-(4-chlorophenyl)-4-hydroxy-1-(5-methylisoxazol-3-yl)-5-oxo-2,5-dihydro-1H-pyrrol-3-yl]-N-(4-methoxyphenyl)acetamido}-2-(4-methoxyphenyl)acetamide methanol monosolvate: single-crystal X-ray diffraction study and Hirshfeld surface analysis

The title compound, C36H37ClN4O7·CH3OH, which crystallizes as a methanol solvate, may possess biological activity, which is inherent for a natural peptide or protein. In the crystal, molecules of the title compound form hydrogen-bonded tetramers with the solvate molecules acting as bridges as a result of the O—H...O and N—H...O intermolecular hydrogen bonds. Hirshfeld surface analysis was used to study the different types of intermolecular interactions whose contributions are: H...H = 53.8%, O...H/H...O = 19.0%, C...H/H...C = 14.8%, Cl...H/H...Cl = 5.3%, N...H/H...N = 3.2%.

Antimicrobial Activity and Toxicity of Analogs of Wasp Venom EMP Peptides. Potential Influence of Oxidized Methionine

The antibiotic and toxic properties for four synthetic analogs of eumenine mastoparan peptides (EMP) have been tested. These properties were compared to two natural peptides found in the venom of solitary wasps Anterhynchium flavomarginatum micado (natural peptide EMP-AF) and Eumenes rubrofemoratus (natural peptide EMP-ER), respectively. Only EMP-AF-OR showed concentration-dependent growth inhibition against all bacterial species tested. Gram positive species had MIC values of 10 μg/mL for B. subtilis and 25 μg/mL for S. aureus. Gram negative species had MIC values of 25 μg/mL for E. coli and 200 μg/mL for P. aeruginosa. Of the other tested peptides, EMP-ER-D2K2 also showed activity and inhibited growth of Bacillus subtilis in a concentration-dependent manner at 200 μg/mL. Peptide EMP-ER-OR reduced the final density of Escherichia coli and B. subtilis cultures but did not impact their growth kinetics. Peptides EMP-AF-OR, EMP-ER-OR, and EMP-ER-D2K2 showed limited antifungal activity against Candida albicans or Histoplasma capsulatum. The hemolytic activity of the analogs were moderated though reports of the natural peptides, especially EMP-AF-OR, already showed low toxicity against erythrocytes. These results are discussed in the context of the potential influence of oxidized methionine on EMP activity.

Specific Interactions Between The Alkaline Protease of P. Aeruginosa And Its Natural Peptide Inhibitor: Ab Initio Molecular Simulations

Alkaline protease aeruginolysin (APR) is an important virulence factor in the evasion of the immune system by Pseudomonas aeruginosa (P. aeruginosa). The P. aeruginosa genome also encodes the highly potent and specific APR peptide inhibitor (APRin). However, the structural reason for the significant inhibition has not been revealed. Using ab initio molecular simulations, we here investigated the specific interactions between APR and APRin to elucidate which amino acid residues of APRin and APR contribute strongest to the inhibition. Since APR has a Zn ion at the ligand-binding site, and histidine and glutamic acid residues are coordinated with Zn, it is essential to precisely describe these coordination bonds to elucidate the specific interactions between APR and APRin. Therefore, we employed the ab initio fragment molecular orbital method to investigate the specific interactions at an electronic level. The results revealed that Ser1 and Ser2 at the N-terminal of APRin significantly contribute to the binding between APRin and APR. In particular, Ser1 binds strongly to Zn as well as to the sidechains of Hid176, Hid180, and Hid186 in APR. This is the main reason for the strong interaction between APR and APRin. The results also elucidated significant contributions of the positively charged Arg83 and Arg90 residues of APRin to the binding with APR. These findings may provide information useful for the design of novel small agents as potent APR inhibitors.