Carbonyl-to-Alkyne Electron Donation Effects in up to 10-nm-Long, Unimolecular Oligo(p-phenylene ethynylenes)

We synthesized some of the longest unimolecular oligo(p-phenylene ethynylenes) (OPEs), which are fully substituted with electron-withdrawing ester groups. An iterative convergent/divergent (a.k.a. iterative exponential growth – IEG) strategy based on Sonogashira couplings was utilized to access these sequence-defined macromolecules with up to 16 repeating units and 32 ester substituents. The carbonyl groups of the ester substituents interact with the triple bonds of the OPEs, leading to (i) unusual, angled triple bonds with increased rotational barrier, (ii) enhanced conformational disorder, and (iii) associated broadening of the UV/Vis absorption spectrum. Our results demonstrate that fully air-stable, unimolecular OPEs with ester groups can readily be accessed with IEG chemistry, providing new macromolecular backbones with unique geometrical, conformational, and photophysical properties.

Beyond B-Cell Epitopes: Curating Positive Data on Antipeptide Paratope Binding to Support Peptide-Based Vaccine Design

Background: B-cell epitope prediction is a computational approach originally developed to support the design of peptide-based vaccines for inducing protective antibody-mediated immunity, as exemplified by neutralization of biological activity (e.g., pathogen infectivity). Said approach is benchmarked against experimentally obtained data on paratope-epitope binding; but such data are curated primarily on the basis of immune-complex structure, obscuring the role of antigen conformational disorder in the underlying immune recognition process. Objective: This work aimed to critically analyze the curation of epitope-paratope binding data that are relevant to B-cell epitope prediction for peptide-based vaccine design. Methods: Database records on neutralizing monoclonal antipeptide antibody immune-complex structure were retrieved from the Immune Epitope Database (IEDB) and analyzed in relation to other data from both IEDB and external sources including the Protein Data Bank (PDB) and published literature, with special attention to data on conformational disorder among paratope-bound and unbound peptidic antigens. Results: Data analysis revealed key examples of antipeptide antibodies that recognize conformationally disordered B-cell epitopes and thereby neutralize the biological activity of cognate targets (e.g., proteins and pathogens), with inconsistency noted in the mapping of some epitopes due to reliance on immune-complex structural details, which vary even among experiments utilizing the same paratope-epitope combination (e.g., with the epitope forming part of a peptide or a protein). Conclusion: The results suggest an alternative approach to curating paratope-epitope binding data based on neutralization of biological activity by polyclonal antipeptide antibodies, with reference to immunogenic peptide sequences and their conformational disorder in unbound antigen structures.

Single-exponential solid-state delayed fluorescence decay in TADF compounds with minimized conformational disorder

Thermally activated delayed fluorescence (TADF) compounds with rapid triplet upconversion in solutions frequently yields drastically lowered upconversion rates in solid hosts due to the conformational disorder, resulting in prolonged multiexponential...

Conformational disorder enabled emission phenomena in heavily doped TADF films

Thermally activated delayed fluorescence (TADF) compounds doped in solid hosts are prone to undergo solvation effects, similar to those as in solution state. Emission peak shifts and changes in emission...

Conformational entropy limits the transition from nucleation to elongation in amyloid aggregation

The formation of amyloid fibrils in Alzheimer’s disease and other neurodegenerative disorders is limited by a slow nucleation step due to the entropic cost to initiate the ordered cross-β structure. While the barrier can be lowered if the molecules maintain conformational disorder, poorly ordered clusters provide a poor binding surface for new molecules. To understand these opposing factors, we used all-atom simulations to parameterize a lattice model that treats each amino acid as a binary variable with β-sheet and non-β states. We find that the optimal degree of order in a nucleus depends on protein concentration. Low concentration systems require more ordered nuclei to capture infrequent monomer attachments. The nucleation phase transitions to the elongation phase when the β-sheet core becomes large enough to overcome the initiation cost, at which point further ordering becomes favorable and the nascent fibril efficiently captures new molecules.

Hydronium bis(trifluoromethanesulfonyl)amide–18-crown-6 (1/1)

The structure of the title compound, H3O+·C2F6NO4S2 −·C12H24O6 or [H3O+·C12H24O6][N(SO2CF3)2 −], which is an ionic liquid with a melting point of 341–343 K, has been determined at 113 K. The asymmetric unit consists of two crystallographically independent 18-crown-6 molecules, two hydronium ions and two bis(trifluoromethanesulfonyl)amide anions; each 18-crown-6 molecule complexes with a hydronium ion. In one 18-crown-6 molecule, a part of the ring exhibits conformational disorder over two sets of sites with an occupancy ratio of 0.533 (13):0.467 (13). One hydronium ion is complexed with the ordered 18-crown-6 molecule via O—H...O hydrogen bonds with H2OH...OC distances of 1.90 (6)–2.19 (7) Å, and the other hydronium ion with the disordered crown molecule with distances of 1.85 (6)–2.36 (6) Å. The hydronium ions are also linked to the anions via O—H...F hydrogen bonds. The crystal studied was found to be a racemic twin with a component ratio of 0.55 (13):0.45 (13).