The importance of molecular complexity in the design of screening libraries

The one-dimensional model of Hann et al. (J Chem Inf Comput Sci 41(3):856–864) has been extended to include reverse binding and wrap-around interaction modes between the protein and ligand to explore the complete combinatorial matrix of molecular recognition. The cumulative distribution function of the Maxwell–Boltzmann distribution has been used to calculate the probability of measuring the sensitivity of the interactions as the asymptotic limits of the distribution better describe the behavior of the interactions under experimental conditions. Based on our model, we hypothesized that molecules of lower complexity are preferred for target based screening campaigns, while augmenting such a library with moieties of moderate complexities maybe better suited for phenotypic screens. The validity of the hypothesis has been assessed via the analysis of the hit rate profiles for four ChemBL datasets for enzymatic and phenotypic screens.     

Biomimetic synthesis of calcium carbonate with different morphologies under the direction of different amino acids

Using three different amino acids (AAs) as organic matrices, including the highly nonpolar hydrophobic l-valine, the positively charged l-arginine and the less polar uncharged l-serine, calcium carbonate (CaCO₃) with different morphologies and polymorphs were synthesized by a facile gas diffusion reaction based on biomimetic strategy. Compared with the control cubic calcite obtained in the absence of AAs, the product from l-valine was cubic calcite aggregates assembled by nano-platelets. The product from l-arginine was spherical vaterite aggregates assembled by spherical nanoparticles. The product from l-serine was the mixture of cubic calcite and spherical vaterite. The structures and properties of the side chains of the AAs exerted the significant effects on the nucleation and growth of the CaCO₃. The formation mechanisms of the CaCO₃ in the presence of AAs are preliminarily discussed. The results suggest that the polymorphs and morphologies of the inorganic nanomaterials might be easily adjusted through the careful selection of the organic matrices.     

Bio-inspired fabrication of well-oriented ZnO nanorod arrays film and its superhydrophobicity and superhydrophilicity

A highly oriented ZnO nanorod array film was fabricated on glass substrate by combinations of Sol–Gel and hydrothermal. The film exhibits perfect superhydrophobicity with a contact angle of 155° and a glide angle of 4° after being surface modified by fluoroalkylsilane, which is similar with wings’ property and structures of large yellow spots mosquitoes. Interestingly, the ZnO nanorods film were converted from superhydrophobicity into superhydrophilicity under ultraviolet light for 2 h due to the decomposition of fluoroalkyl chain of fluoroalkylsilane and the photosensitivity of ZnO surface. The transition mechanisms of wettability are discussed on the basis of correlated theories.     

Microenvironment Effects in Electrocatalysis: Ionic‐Liquid‐Like Coating on Carbon Nanotubes Enhances the Pd‐Electrocatalytic Alcohol Oxidation

A new catalyst consisting of ionic liquid (IL)‐functionalized carbon nanotubes (CNTs) obtained through 1,3‐dipolar cycloaddition support‐enhanced electrocatalytic Pd nanoparticles (Pd@IL(Cl^?)‐CNTs) was successfully fabricated and applied in direct ethanol alkaline fuel cells. The morphology, structure, component and stability of Pd@IL(Cl^?)‐CNTs were systematic characterized by transmission electron microscopy (TEM), high‐resolution transmission electron microscopy (HRTEM), Raman spectra, thermogravimetric analysis (TGA) and X‐ray diffraction (XRD). The new catalyst exhibited higher electrocatalytic activity, better tolerance and electrochemical stability than the Pd nanoparticles (NPs) immobilized on CNTs (Pd@CNTs), which was ascribed to the effects of the IL, larger electrochemically active surface area (ECSA), and greater processing performance. Cyclic voltammograms (CVs) at various scan rates illustrated that the oxidation behaviors of ethanol at all electrodes were controlled by diffusion processes. The investigation of the different counteranions demonstrated that the performance of the IL‐CNTs hybrid material was profoundly influenced by the subtly varied structures of the IL moiety. All the results indicated that the Pd@IL(Cl^?)‐CNTs catalyst is an efficient anode catalyst, which has potential applications in direct ethanol fuel cells and the strategy of IL functionalization of CNTs could be available to prepare other carbonaceous carrier supports to enhance the dispersivity, stability, and catalytic performance of metal NPs as well.     

Synthesis and Properties of Oval‐Shaped Iron Oxide/Ethylene Glycol Mesostructured Nanosheets

We have demonstrated a new and facile bottom‐up protocol for the effective synthesis of oval‐shaped iron oxide/ethylene glycol (FeO_x/EG) mesostructured nanosheets. Deprotonated ethylene glycol molecules are intercalated into iron oxide layers to form an interlayer distance of 10.6 Å. These materials display some peculiar magnetic properties, such as the low Morin temperature T_M and ferromagnetism below this T_M value. CdSe/ZnS nanoparticles can be loaded onto these mesostructured nanosheets to produce nanocomposites that combine both magnetic and fluorescence functions. In addition, iron oxide/propanediol (or butanediol) mesostructured materials with increased interlayer distances can also be synthesized. The developed synthetic strategy may be extended toward the creation of other ultrathin mesostructured nanosheets.     

Exploring the Reactivity of Multicomponent Photocatalysts: Insight into the Complex Valence Band of BiOBr

The band structure of multicomponent semiconductor photocatalysts, as well as their reactivity distinction under different wavelengths of light, is still unclear. BiOBr, which is a typical multicomponent semiconductor, may have two possible valence‐band structures, that is, two discrete valence bands constructed respectively from O 2p and Br 4p orbitals, or one valence band derived from the hybridization of these orbitals. In this work, aqueous photocatalytic hydroxylation is applied as the probe reaction to investigate the nature and reactions of photogenerated holes in BiOBr. Three organic compounds (microcystin‐LR, aniline, and benzoic acid) with different oxidation potentials were selected as substrates. Isotope labeling (H₂¹⁸O as the solvent) was used to determine the source of the O atom in the hydroxyl group of the products, which distinguishes the contribution of different hydroxylation pathways. Furthermore, a spin‐trapping ESR method was used to quantify the reactive oxygen species (^.OH and ^.OOH) formed in the reaction system. The different isotope abundances of the hydroxyl O atom of the products formed, as well as the reverse trend of the ^.OH/^.OOH ratio with the oxidative resistance of the substrate under UV and visible irradiation, reveal that BiOBr has two separate valence bands, which have different oxidation ability and respond to UV and visible light, respectively. This study shows that the band structure of semiconductor photocatalysts can be reliably analyzed with an isotope labeling method.     

Enantioselective Total Synthesis of (−)‐Blennolide A

Blennolide A can be synthesized through an enantioselective domino‐Wacker/carbonylation/methoxylation reaction of 7 a with 96 % ee and an enantioselective Wacker oxidation of 7 b with 89 % ee. Further transformations led to the α,β‐unsaturated ester (E)‐ 17 , which was subjected to a highly selective Michael addition, introducing a methyl group to give 18 a . After a threefold oxidation and an intramolecular acylation, the tetrahydroxanthenone 4 was obtained, which could be transformed into (?)‐blennolide A (ent‐ 1 ) in a few steps.     

Integrated Hollow Mesoporous Silica Nanoparticles for Target Drug/siRNA Co‐Delivery

A hollow mesoporous silica nanoparticle (HMSNP) based drug/siRNA co‐delivery system was designed and fabricated, aiming at overcoming multidrug resistance (MDR) in cancer cells for targeted cancer therapy. The as‐prepared HMSNPs have perpendicular nanochannels connecting to the internal hollow cores, thereby facilitating drug loading and release. The extra volume of the hollow core enhances the drug loading capacity by two folds as compared with conventional mesoporous silica nanoparticles (MSNPs). Folic acid conjugated polyethyleneimine (PEI‐FA) was coated on the HMSNP surfaces under neutral conditions through electrostatic interactions between the partially charged amino groups of PEI‐FA and the phosphate groups on the HMSNP surfaces, blocking the mesopores and preventing the loaded drugs from leakage. Folic acid acts as the targeting ligand that enables the co‐delivery system to selectively bind with and enter into the target cancer cells. PEI‐FA‐coated HMSNPs show enhanced siRNA binding capability on account of electrostatic interactions between the amino groups of PEI‐FA and siRNA, as compared with that of MSNPs. The electrostatic interactions provide the feasibility of pH‐controlled release. In vitro pH‐responsive drug/siRNA co‐delivery experiments were conducted on HeLa cell lines with high folic acid receptor expression and MCF‐7 cell lines with low folic acid receptor expression for comparison, showing effective target delivery to the HeLa cells through folic acid receptor meditated cellular endocytosis. The pH‐responsive intracellular drug/siRNA release greatly minimizes the prerelease and possible side effects of the delivery system. By simultaneously delivering both doxorubicin (Dox) and siRNA against the Bcl‐2 protein into the HeLa cells, the expression of the anti‐apoptotic protein Bcl‐2 was successfully suppressed, leading to an enhanced therapeutic efficacy. Thus, the present multifunctional nanoparticles show promising potentials for controlled and targeted drug and gene co‐delivery in cancer treatment.     

An Investigation of 1:1 Adducts of Gallium Trihalides with Triarylphosphines by Solid‐State 69/71Ga and 31P NMR Spectroscopy

Several 1:1 adducts of gallium trihalides with triarylphosphines, X₃Ga(PR₃) (X=Cl, Br, and I; PR₃=triarylphosphine ligand), were investigated by using solid‐state ^69/71Ga and ³¹P NMR spectroscopy at different magnetic‐field strengths. The ^69/71Ga nuclear quadrupolar coupling parameters, as well as the gallium and phosphorus magnetic shielding tensors, were determined. The magnitude of the ⁷¹Ga quadrupolar coupling constants (C_Q(⁷¹Ga)) range from approximately 0.9 to 11.0 MHz . The spans of the gallium magnetic shielding tensors for these complexes, δ₁₁?δ₃₃, range from approximately 30 to 380 ppm; those determined for phosphorus range from 10 to 40 ppm. For any given phosphine ligand, the gallium nuclei are most shielded for X=I and least shielded for X=Cl, a trend previously observed for In^III–phosphine complexes. This experimental trend, attributed to spin‐orbit effects of the halogen ligands, is reproduced by DFT calculations. The signs of C_Q(^69/71Ga) for some of the adducts were determined from the analysis of the ³¹P NMR spectra acquired with magic angle spinning (MAS). The ¹J(^69/71Ga,³¹P) and ΔJ(^69/71Ga, ³¹P) values, as well as their signs, were also determined; values of ¹J(⁷¹Ga,³¹P) range from approximately 380 to 1590 Hz. Values of ¹J(^69/71Ga,³¹P) and ΔJ(^69/71Ga,³¹P) calculated by using DFT have comparable magnitudes and generally reproduce experimental trends. Both the Fermi‐contact and spin‐dipolar Fermi‐contact mechanisms make important contributions to the ¹J(^69/71Ga,³¹P) tensors. The ³¹P NMR spectra of several adducts in solution, obtained as a function of temperature, are contrasted with those obtained in the solid state. Finally, to complement the analysis of NMR spectra for these adducts, single‐crystal X‐ray diffraction data for Br₃Ga[P(p‐Anis)₃] and I₃Ga[P(p‐Anis)₃] were obtained.