Enzyme Shielding in an Enzyme‐thin and Soft Organosilica Layer

The fragile nature of most enzymes is a major hindrance to their use in industrial processes. Herein, we describe a synthetic chemical strategy to produce hybrid organic/inorganic nanobiocatalysts; it exploits the self‐assembly of silane building blocks at the surface of enzymes to grow an organosilica layer, of controlled thickness, that fully shields the enzyme. Remarkably, the enzyme triggers a rearrangement of this organosilica layer into a significantly soft structure. We demonstrate that this change in stiffness correlates with the biocatalytic turnover rate, and that the organosilica layer shields the enzyme in a soft environment with a markedly enhanced resistance to denaturing stresses.     

Hyperconjugative interactions are the main responsible for the anomeric effect: a direct relationship between the hyperconjugative anomeric effect,global hardness and zero-point energy

The correlations between the global hardness (η), hyperconjugative anomeric effect, Pauli exchange-type repulsions, electrostatic model associated with dipole–dipole interaction and structural parameters in 2-fluorotetrahydropyran, -thiopyran, -selenopyran (1–3) and their chloro- (4–6) and bromo-analogs (7–9) were investigated by means of the conventional and range-corrected functionals and natural bond orbital (NBO) interpretation. By deletion of the HC-exo-AE and HC-endo-AE, the equatorial conformations of compounds 1–9 become more stable than their corresponding axial forms, revealing that anomeric relationships in compounds 1–9 have the hyperconjugative anomeric effect origins while the electrostatic model associated with dipole–dipole interaction does not play a determining role on the variations of the anomeric relationships in these compounds. The anomeric relationships in compounds 1–3 have no Pauli exchange-type repulsions origin, but it has a significant impact on the conformational preferences in compounds 4–6 and 7–9. A canonical molecular orbital interpretation was conducted to investigate the correlations between the linear combinations of natural bond orbitals in the HOMOs, LUMOs and the global hardness (η) values. There is a direct relationship between the hyperconjugative anomeric effect, global hardness (η) and zero-point energies in compounds 1–3, 4–6 and 7–9. The harder axial conformations with the greater hyperconjugative anomeric effect and zero-point energy values are more stable than their corresponding equatorial forms.     

Semisynthetic Derivatives of Selected Amaryllidaceae Alkaloids as a New Class of Antimycobacterial Agents

The search for novel antimycobacterial drugs is a matter of urgency, since tuberculosis is still one of the top ten causes of death from a single infectious agent, killing more than 1.4 million people worldwide each year. Nine Amaryllidaceae alkaloids (AAs) of various structural types have been screened for their antimycobacterial activity. Unfortunately, all were considered inactive, and thus a pilot series of aromatic esters of galanthamine, 3-O-methylpancracine, vittatine and maritidine were synthesized to increase biological activity. The semisynthetic derivatives of AAs were screened for their in vitro antimycobacterial activity against Mycobacterium tuberculosis H37Ra and two other mycobacterial strains (M. aurum, M. smegmatis) using a modified Microplate Alamar Blue Assay. The most active compounds were also studied for their in vitro hepatotoxicity on the hepatocellular carcinoma cell line HepG2. In general, the derivatization of the original AAs was associated with a significant increase in antimycobacterial activity. Several pilot derivatives were identified as compounds with micromolar MICs against M. tuberculosis H37Ra. Two derivatives of galanthamine, 1i and 1r, were selected for further structure optimalization to increase the selectivity index.     

Bioapplications of poly(amidoamine) (PAMAM) dendrimers in nanomedicine

Poly(amidoamine) (PAMAM) dendrimers are a novel class of spherical, well-designed branching polymers with interior cavities and abundant terminal groups on the surface which can form stable complexes with drugs, plasmid DNA, oligonucleotides, and antibodies. Amine‐terminated PAMAM dendrimers are able to solubilize different families of hydrophobic drugs, but the cationic charges on dendrimer surface may disturb the cell membrane. Therefore, surface modification by PEGylation, acetylation, glycosylation, and amino acid functionalization is a convenient strategy to neutralize the peripheral amine groups and improve dendrimer biocompatibility. Anticancer agents can be either encapsulated in or conjugated to dendrimer and be delivered to the tumor via enhanced permeability and retention (EPR) effect of the nanoparticle and/or with the help of a targeting moiety such as antibody, peptides, vitamins, and hormones. Biodegradability, non-toxicity, non-immunogenicity, and multifunctionality of PAMAM dendrimer are the key factors which facilitate steady increase of its application in drug delivery, gene transfection, tumor therapy, and diagnostics applications with precision and selectivity. This review deals with the major topics of PAMAM dendrimers including structure, synthesis, toxicity, surface modification, and also possible new applications of these spherical polymers in biomedical fields as dendrimer-based nanomedicine.     

Monolayers of an amphiphilic para-carboxy-calix[4]arene act as templates for the crystallization of acetaminophen

The title compound, 5,11,17,23-tetra-carboxy-25,26,27,28-tetradodecyloxy-calix[4]arene, 1, has been studied at the air–water interface, self-assembled as Langmuir monolayers, for its ability to interact with an active pharmaceutical ingredient (API), acetaminophen (APAP), and to initiate its crystallization. The Π/A isotherm study shows that there is a clear interaction between 1 and APAP causing an expansion of the monolayer. In addition to the known phase transition occurring at a surface tension of 38 mN m^?1, an additional kink is observed in the compression isotherm for concentrations of APAP above 40 mM suggesting that this API is causing an additional phase transition of the monolayer. Interface-initiated crystallization studies show that the presence of a monolayer spread on a supersaturated solution of APAP (26 g L^?1) triggers this API crystal growth from the interface. The transfer of 1-based monolayers on glass surfaces has been carried out using the Langmuir–Blodgett technique. The so-produced monolayers have been shown to template the crystallization of APAP. LB films of 1 have characterized using imaging and spectroscopic ellipsometry. The results suggest that each monolayer has an average thickness of 18 Å, which is consistent with the molecular structure of 1 self-organized parallel to the interface with the alkyl chains pointing out parallel to the axis of the macrocycle and without interdigitation of the alkyl chains. The presence of APAP in the subphase during the LB transfer causes a limited but relevant increase in the layer thickness. The study of the capabilities of the LB films to initiate crystallization of APAP is also demonstrated showing the influence of the monolayer packing on the quantity of formed crystals.     

An organic‐inorganic heterogeneous catalyst based on Keplerate polyoxometalates for oxidation of dibenzothiophene derivatives with Hydrogen peroxide

An organic‐inorganic material (NH₄)₂(MimAM)₄₀[Mo₁₃₂O₃₇₂(CH₃COO)₃₀(H₂O)₇₂] have been synthesized by reacting [(NH₄)₄₂[Mo^VI₇₂ Mo^V₆₀O₃₇₂(CH₃COO)₃₀(H₂O)₇₂] with the ionic liquid 3‐Aminoethyl‐1‐methylimidazolium bromide. The catalyst showed remarkably a high catalytic performance in the oxidation of dibenzothiophene (DBT) derivatives with H₂O₂ 35% as a safe and green oxidant. The main parameters affecting the process including catalyst, acid additive, hydrogen peroxide amounts and temperature have been investigated in detail. Sulfur removal of DBT in n‐heptane reached to 98.3% yield at 40 °C using 2.5 mmol H₂O₂ and 100 mg of (NH₄)₂(MimAM)₄₀[Mo₁₃₂O₃₇₂(CH₃COO)₃₀(H₂O)₇₂] after 90 min. Under the optimal conditions, BT (benzothiophene), DBT (dibenzothiophene) and 4,6‐DMDBT (4,6‐dimethyl‐dibenzothiophene) achieved high desulfurization efficiency. Our results showed that the reactivity order of different model sulfur compounds are thiophene <4,6‐dimethyl dibenzothiophene< dibenzothiophene. The catalysts could be easily separated from the reaction solution by simple filtration and recycled for several times without loss of activity.     

M(HSO4)n-Promoted Synthesis of 2-Aryl-1-arylmethyl-1H-1,3-benzimidazole Derivatives

We have developed a highly selective synthesis of 2-aryl-1-arylmethyl-1H-1,3-benzimidazoles from the reaction of o-phenylenediamines and aromatic aldehydes in the presence of metal hydrogen sulfates [M(HSO₄)_n] in water and also under solvent-free conditions in good to excellent yields.     

NBO,NMR Analysis,and Hybrid DFT Study of Structural and Configurational Properties of Di-tert-butyl-, bis(trimethysilyl)-, Bis(trimethgermyl)-, and Bis(trimethylstannyl)- cyclopenta-1,3-dienes

Abstract

The alkyl 1,2-shift in di-tert-butylcyclopenta-1,3-diene (1) and the metallotropic 1,2-shifts in bis(trimethylsilyl)cyclopenta-1,3-diene (2), bis(trimethylgermyl)cyclopenta-1,3-diene (3), and bis(trimethylstannyl)cyclopenta-1,3-diene (4) have been investigated by means of natural bond orbital (NBO), nuclear magnetic resonance (NMR) analysis, and hybrid density functional theory based methods. The B3LYP/DZVP results showed that the M(CH₃)₃ group [M = C (1), Si (2), Ge (3), and Sn (4)] migration barrier heights around cyclopentadienyl rings decrease from di-tert-butylcyclopenta-1,3-diene to its stannane derivative. Also, based on the results obtained, the stabilities of the 5,5-isomers in comparison to the 1,5- and 2,5-isomers increase from di-tert-butylcyclopenta-1,3-diene to its stannane derivative. The results suggest that in these compounds the metallotropic shifts are controlled by the stabilization energies associated with σ→π* electron delocalizations and the increase of the σ_C5-M→π*_C1-C2 electron delocalizations facilitates the M(CH₃)₃ group migrations around cyclopentadienyl rings. Based on the aromatic stabilization energy (ASE) values calculated, the aromaticity increases from the 5,5-isomers of di-tert-butylcyclopenta-1,3-diene to its stannane derivative but the variation of the nucleus-independent chemical shift, NICS(0) and NICS(1), values calculated are not in accordance with the ASE values calculated and the σ_C5-M→π*_C1-C2

electron delocalizations. The correlations between the sigmatropic shift barrier heights, σ→π* electron delocalizations, ASE, and NICS values were investigated.

GRAPHICAL ABSTRACT