Solvent Remodeling in Single-Chain Amphiphilic Heteropolymer Systems

Through molecular dynamics simulations, we demonstrate how single-chain nanoparticles (SCNPs) assembled via transient linkages in water can remodel in organic solvent. Methacrylate-based random heteropolymers (RHPs) have shown promise in an assortment of applications that harness their bio-inspired properties. While their molecular behavior has been broadly characterized in water, many newer applications include the use of organic solvent rather than bio-mimetic conditions in which the polymer assemblies, typically driven by the hydrophobic effect, are less well understood. Here, we examine a specific RHP system which forms compact globular morphologies in highly polar and non-polar environments while adopting extended conformations in solvents of intermediate polarity. We also demonstrate the pivotal role of electrostatic interactions between charge groups in low dielectric mediums. Finally, we compare high temperature anneal cycles to room temperature equilibrations to illuminate activation barriers to remodeling upon environmental changes.

Structure and in silico simulations of a cold-active esterase reveals its prime cold-adaptation mechanism

Here we determined the structure of a cold active family IV esterase (EstN7) cloned from Bacillus cohnii strain N1. EstN7 is a dimer with a classical α/β hydrolase fold. It has an acidic surface that is thought to play a role in cold-adaption by retaining solvation under changed water solvent entropy at lower temperatures. The conformation of the functionally important cap region is significantly different to EstN7's closest relatives, forming a bridge-like structure with reduced helical content providing greater access to the active site through more than one substrate access tunnel. However, dynamics do not appear to play a major role in cold adaption. Molecular dynamics at different temperatures, rigidity analysis, normal mode analysis and geometric simulations of motion confirm the flexibility of the cap region but suggest that the rest of the protein is largely rigid. Rigidity analysis indicates the distribution of hydrophobic tethers is appropriate to colder conditions, where the hydrophobic effect is weaker than in mesophilic conditions due to reduced water entropy. Thus, it is likely that increased substrate accessibility and tolerance to changes in water entropy are important for of EstN7's cold adaptation rather than changes in dynamics.

Broad ultra-potent neutralization of SARS-CoV-2 variants by monoclonal antibodies specific to the tip of RBD

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) continue to wreak havoc across the globe. Higher transmissibility and immunologic resistance of VOCs bring unprecedented challenges to epidemic extinguishment. Here we describe a monoclonal antibody, 2G1, that neutralizes all current VOCs and has surprising tolerance to mutations adjacent to or within its interaction epitope. Cryo-electron microscopy structure showed that 2G1 bound to the tip of receptor binding domain (RBD) of spike protein with small contact interface but strong hydrophobic effect, which resulted in nanomolar to sub-nanomolar affinities to spike proteins. The epitope of 2G1 on RBD partially overlaps with ACE2 interface, which gives 2G1 ability to block interaction between RBD and ACE2. The narrow binding epitope but high affinity bestow outstanding therapeutic efficacy upon 2G1 that neutralized VOCs with sub-nanomolar IC50 in vitro. In SARS-CoV-2 and Beta- and Delta- variant-challenged transgenic mice and rhesus macaque models, 2G1 protected animals from clinical illness and eliminated viral burden, without serious impact to animal safety. Mutagenesis experiments suggest that 2G1 could be potentially capable of dealing with emerging SARS-CoV-2 variants in future. This report characterized the therapeutic antibodies specific to the tip of spike against SARS-CoV-2 variants and highlights the potential clinical applications as well as for developing vaccine and cocktail therapy.

Organocatalytic Asymmetric Michael Addition in Aqueous Media by a Hydrogen-Bonding Catalyst and Application for Inhibitors of GABAB Receptor

Catalysts based on (R, R)-1,2-diphenylethylenediamine are, as chiral organic catalysts, applied to the asymmetric Michael addition to α, β-unsaturated nitroalkenes under neutral conditions. The role of an aqueous medium for organic catalytic activity can be reversed concerning hydrophilic-hydrophobic function depending on the reaction conditions. In this study, to provide an environmentally friendly system, the thiourea-based catalyst substituted with 3,5-(CF3)2-Ph was used in water solvents. The hydrophobic effect of the substituent provided fast reaction, high chemical yield, and mirror-image selectivity. This reaction allowed the preparation of GABAB agonists in an optically pure manner. Additionally, GABA (γ-aminobutyric acid) analogs such as baclofen and phenibut were synthesized as R-type S-type with high optical purity.

A super-efficient and biosafe hemostatic cotton gauze with controlled balance of hydrophilicity/hydrophobicity and tissue adhesiveness

Cotton gauze is a widely used topical hemostatic material for bleeding control in military and civil accidents and surgical operations, but its high blood absorption capacity tends to cause extra blood loss of the wounded person, which may increase the risk of shock and death. Therefore, development of rapid hemostatic cotton gauze with less blood loss is of great significance. Herein, we prepared a super-efficient hemostatic cotton gauze whose surface was slightly modified with a catechol compound which features a flexible long hydrophobic alkyl chain terminated with a catechol group. Its hemostatic performance in rat and pig injury models was far superior to standard cotton gauze and Combat GauzeTM. The latter is a well-known commercial gauze for controlling massive hemorrhaging. Additionally, after stoppage of bleeding, the wound sites hardly re-bleed upon the gauze was peeled off. Histological analysis proved that the novel cotton gauze well kept the biosafety of cotton gauze. Interestingly, a similar impressive hemostatic performance was also achieved for chitosan nonwoven gauze modified with the same procedure. Density functional theory calculation and instrumental measurements demonstrate that their extraordinary hemostatic capability is attributable to the highly efficient formation of big and thick primary blood clot made of massive aggregated erythrocytes, due to gauze’s effective controlling of blood movement through its blocking effect from tissue adhesion by catechol, platelet activation by cotton fiber, blood absorption by cotton, and hydrophobic effect from long alkyl chain. The methodology and hemostatic mechanisms presented in this work may open a new avenue for developing highly efficient hemostatic gauzes.

Porous carbon aerogel derived from bacterial cellulose with prominent potential for efficient removal of antibiotics from the aquatic matrix

The development of adsorption methods for the remediation of antibiotics pollution in water is hindered by the lack of high-performance sorbents. In this study, a nanofiber carbon aerogel was prepared using bacterial cellulose and its adsorption performances for three common antibiotics (norfloxacin, sulfamethoxazole, and chloramphenicol) in water were evaluated. The as-prepared nanofiber carbon aerogel showed a higher adsorption capacity toward target antibiotics compared to other adsorbents reported in the literature. The maximum adsorption capacities for norfloxacin, sulfamethoxazole, and chloramphenicol were 1,926, 1,264, and 525 mg/g, respectively at 298 K. Notably, the nanofiber carbon aerogel was able to adsorb 80% of the equilibrium adsorption capacity within 1 min and reach equilibrium within 15 min. After five regeneration cycles, the adsorption capacity still reached 1,166, 847, and 428 mg/g for norfloxacin, sulfamethoxazole, and chloramphenicol, respectively. The characterization results showed that the carbon aerogel exhibited a high specific surface area (1,505 m2/g) and a layered porous network structure. Furthermore, the mechanistic study reveals that the enhanced antibiotic adsorption by the as-prepared nanofiber carbon aerogel was attributed to the pore filling effect, hydrogen bonding, hydrophobic effect, electrostatic interaction, and π-π interactions. Overall, these results imply that low-cost and green nanofiber carbon aerogels may be promising adsorbents for the remediation of antibiotic-contaminated wastewater. The materials prepared from natural and readily available bacterial cellulose can adsorb antibiotics efficiently, which provides a reference for the development of adsorbent materials using natural substances.

Polymer for Internal Hydrophobization of Cement-Based Materials: Design, Synthesis, and Properties

A series of novel comb-like poly(butyl acrylate)-g-poly(dimethylaminoethyl methacrylate) (PBA-g-PDMAEMA) with different side chain lengths were designed and successfully synthesized by the “first main chain then side chain” method. Infrared Spectroscopy (IR), 1H Nuclear Magnetic Resonance (1H NMR), and gel permeation chromatography (GPC) were used for structural confirmation and molecular weight characterization. This polymer exhibited responsive behavior from hydrophilicity to hydrophobicity under the alkaline environment of cement-based materials, with the contact angle of 105.6°, a decreased evaporation rate, and a hydrophile–lipophile balance (HLB) value. A significant internal hydrophobic effect on cement mortar was shown in the water absorption rate, which decreased by 75.2%, and a dry shrinkage-reducing rate of more than 30%. Furthermore, this polymer can effectively slow the exothermic rate, reduce the heat release, and delay the exothermic peak of cement hydration. It was interesting that these properties showed a direct correlation with the side chain length of the comb polymer. The aims of this study are to provide a new avenue to synthesize polymers with the spontaneous hydrophilicity–hydrophobicity transition in the cement system, achieving excellent internal hydrophobicity of cement-based materials, and to offer a promising alternative to resist external erosion for improving the durability and service life of cement-based materials.

Contiguously-hydrophobic sequences are functionally significant throughout the human exome

Hydrophobic interactions have long been established as essential to stabilizing structured proteins as well as drivers of aggregation, but the impact of hydrophobicity on the functional significance of sequence variants has rarely been considered in a genome-wide context. Here we test the role of hydrophobicity on functional impact using a set of 70,000 disease and non-disease associated single nucleotide polymorphisms (SNPs), using enrichment of disease-association as an indicator of functionality. We find that functional impact is uncorrelated with hydrophobicity of the SNP itself, and only weakly correlated with the average local hydrophobicity, but is strongly correlated with both the size and minimum hydrophobicity of the contiguous hydrophobic domain that contains the SNP. Disease-association is found to vary by more than 6-fold as a function of contiguous hydrophobicity parameters, suggesting utility as a prior for identifying causal variation. We further find signatures of differential selective constraint on domain hydrophobicity, and that SNPs splitting a long hydrophobic region or joining two short regions of contiguous hydrophobicity are particularly likely to be disease-associated. Trends are preserved for both aggregating and non-aggregating proteins, indicating that the role of contiguous hydrophobicity extends well beyond aggregation risk.Statement of SignificanceProteins rely on the hydrophobic effect to maintain structure and interactions with the environment. Surprisingly, no signs that amino acid hydrophobicity influences natural selection have been detected using modern genetic data. This may be because analyses that treat each amino acid separately do not reveal significant results, which we confirm here. However, because the hydrophobic effect becomes more powerful as more hydrophobic molecules are introduced, we tested whether unbroken stretches of hydrophobic amino acids are under selection. Using genetic variant data from across the human genome, we found evidence that selection pressure increases continually with the length of the unbroken hydrophobic sequence. These results could lead to improvements in a wide range of genomic tools as well as insights into disease and protein evolutionary history.

The Role of Counterions in Intermolecular Radical Coupling of Ru-bda Catalysts

Intermolecular radical coupling (also interaction of two metal centers I2M) is one of the main mechanisms for O–O bond formation in water oxidation catalysts. For Ru(bda)L2 (H2bda = 2,2′-bipyridine-6,6′-dicarboxylate, L = pyridine or similar nitrogen containing heterocyclic ligands) catalysts a significant driving force in water solution is the hydrophobic effects driven by the solvent. The same catalyst has been successfully employed to generate N2 from ammonia, also via I2M, but here the solvent was acetonitrile where hydrophobic effects are absent. We used a classical force field for the key intermediate [RuVIN(bda)(py)2]+ to simulate the dimerization free energy by calculation of the potential mean force, in both water and acetonitrile to understand the differences and similarities. In both solvents the complex dimerizes with similar free energy profiles. In water the complexes are essentially free cations with limited ion paring, while in acetonitrile the ion-pairing is much more significant. This ion-pairing leads to significant screening of the charges, making dimerization possible despite lower solvent polarity that could lead to repulsion between the charged complexes. In water the lower ion pairing is compensated by the hydrophobic effect leading to favorable dimerization despite repulsion of the charges. A hypothetical doubly charged [RuVIIN(bda)py2]2+ was also studied for deeper understanding of the charge effect. Despite the double charge the complexes only dimerized favorably in the lower dielectric solvent acetonitrile, while in water the separated state is more stable. In the doubly charged catalyst the effect of ion-pairing is even more pronounced in acetonitrile where it is fully paired similar to the 1+ complex, while in water the separation of the ions leads to greater repulsion between the two catalysts, which prevents dimerization. Graphic Abstract