Non-Fullerene Acceptors with Direct and Indirect Hexa-fluorination Afford >17% Efficiency in Polymer Solar Cells

The rational molecular design of non-fullerene acceptors (NFAs) in organic solar cells (OSCs) can profoundly influence photovoltaic (OPV) performance. NFA fluorination has to date proven beneficial to cell performance. However,...

A deeper exploration of the relation between sulfonation degree and retanning performance of aromatic syntans

It is well-known that the sulfonation degree (DS) of aromatic syntan is an important factor affecting its retanning performances. But the quantitative relation between DS and syntan property and the influencing mechanism of DS on syntan property are not clarified. In this work, five phenolic formaldehyde syntans (PFSs) with the same polymerization degree but varying DS were prepared to investigate the effect of DS on the properties of syntan and crust leather. It was found that the absolute value of zeta potential and the particle size of PFS decreased with increasing DS in aqueous solution. Molecular dynamic simulation results proved that the DS of PFS was a major contributor to electrostatic interaction and hydrogen bonding in the PFS–water system and greatly affected the aggregation and dispersion of PFS in aqueous solution. The PFS with a low DS was prone to aggregate to large particles in aqueous solution because of low intermolecular electrostatic repulsion and less hydrogen bonds and therefore can be used to increase the thickness and tightness of leather. The PFS with a high DS presented a small particle size with more anionic groups in aqueous solution, thereby sharply decreasing the positive charge of leather surface and facilitating the penetration of the post-tanning agents into the leather. These results might be scientifically valid for rational molecular design of syntans and more productive use of syntans in leather making. Graphical Abstract

Identifying signatures of proteolytic stability and monomeric propensity in O-glycosylated insulin using molecular simulation

Insulin has been commonly adopted as a peptide drug to treat diabetes given its ability to facilitate the uptake of glucose from the blood. The development of oral insulin remains elusive over decades owing to its susceptibility to the enzymes in the gastrointestinal tract and poor permeability through the intestinal epithelium upon dimerization. Recent experimental studies have revealed that certain O-linked glycosylation patterns could enhance insulin’s proteolytic stability and reduce its dimerization propensity, but the understanding of such phenomena at the molecular level is still evasive. To address this challenge, we propose and test several structural determinants that could potentially in uence insulin’s proteolytic stability and dimerization propensity. We used these as the metrics to assess the properties of interest from 10 s aggregate molecular dynamics of each of 12 targeted insulin glyco-variants from multiple wild-type crystal structures. We found that glycan-involved hydrogen bonds and glycan-dimer occlusion were useful metrics predicting the proteolytic stability and dimerization propensity of insulin, as was in part the solvent accessible surface area of proteolytic sites, while other plausible metrics were not generally predictive. This work helps better explain how O-linked glycosylation in uences the proteolytic stability and monomeric propensity of insulin, illuminating a path towards rational molecular design of insulin glycoforms.

Identifying signatures of proteolytic stability and monomeric propensity in O-glycosylated insulin using molecular simulation

Insulin has been commonly adopted as a peptide drug to treat diabetes given its ability to facilitate the uptake of glucose from the blood. The development of oral insulin remains elusive over decades owing to its susceptibility to the enzymes in the gastrointestinal tract and poor permeability through the intestinal epithelium upon dimerization. Recent experimental studies have revealed that certain O-linked glycosylation patterns could enhance insulin’s proteolytic stability and reduce its dimerization propensity, but the understanding of such phenomena at the molecular level is still evasive. To address this challenge, we propose and test several structural determinants that could potentially in uence insulin’s proteolytic stability and dimerization propensity. We used these as the metrics to assess the properties of interest from 10 s aggregate molecular dynamics of each of 12 targeted insulin glyco-variants from multiple wild-type crystal structures. We found that glycan-involved hydrogen bonds and glycan-dimer occlusion were useful metrics predicting the proteolytic stability and dimerization propensity of insulin, as was in part the solvent accessible surface area of proteolytic sites, while other plausible metrics were not generally predictive. This work helps better explain how O-linked glycosylation in uences the proteolytic stability and monomeric propensity of insulin, illuminating a path towards rational molecular design of insulin glycoforms.