应用多层网络进行分子拓扑结构与物性的关联

应用具有极强非线性映射能力，且能以任意精度逼近函数的多层网络进行分子拓扑指数与性质关联。集中研究了烷烃的三个物性（沸点、临界温度和临界压力）与结构的关系，其中烷烃结构利用ａｄｈｏｃ指数描述；多层网络的学习算法则采用共轭梯度算法。所得结果良好，从而以非常简单的方式有效地实现了指数与性质的关联。     

分子电性作用矢量用于合成产率预测

应用分子电性作用矢量(molecular electronegativity interaction vector,MEIV)建立了42种Wittig反应产率的定量构效关系模型,考察了反应物分子结构对合成产率的内在影响。结合多元线性回归、逐步回归变量筛选方法和QSAR建模技术,得到7参数QSAR模型,交互校验的复相关系数分别为0.985、0.973;选用外部集对模型健壮性、预测能力进行考察,亦获得良好结果:R=0.984、R=0.965。模型稳定性良好,预测能力颇强。     

Molecular fingerprint and machine learning to accelerate design of high-performance homochiral metal–organic frameworks

Computational screening was employed to calculate the enantioseparation capabilities of 45 functionalized homochiral metal–organic frameworks (FHMOFs), and machine learning (ML) and molecular fingerprint (MF) techniques were used to find new FHMOFs with high performance. With increasing temperature, the enantioselectivities for (R,S)-1,3-dimethyl-1,2-propadiene are improved. The “glove effect” in the chiral pockets was proposed to explain the correlations between the steric effect of functional groups and performance of FHMOFs. Moreover, the neighborhood component analysis and RDKit/MACCS MFs show the highest predictive effect on enantioselectivities among the four ML classification algorithms with nine MFs that were tested. Based on the importance of MF, 85 new FHMOFs were designed, and a newly designed FHMOF, NO₂-NHOH-FHMOF, with high similarity to the optimal MFs achieved improved chiral separation performance, with enantioselectivities of 85%. The design principles and new chiral pockets obtained by ML and MFs could facilitate the development of new materials for chiral separation.     

Molecular Biology in Treatment Decision Processes—Neuro-Oncology Edition

Computational approaches including machine learning, deep learning, and artificial intelligence are growing in importance in all medical specialties as large data repositories are increasingly being optimised. Radiation oncology as a discipline is at the forefront of large-scale data acquisition and well positioned towards both the production and analysis of large-scale oncologic data with the potential for clinically driven endpoints and advancement of patient outcomes. Neuro-oncology is comprised of malignancies that often carry poor prognosis and significant neurological sequelae. The analysis of radiation therapy mediated treatment and the potential for computationally mediated analyses may lead to more precise therapy by employing large scale data. We analysed the state of the literature pertaining to large scale data, computational analysis, and the advancement of molecular biomarkers in neuro-oncology with emphasis on radiation oncology. We aimed to connect existing and evolving approaches to realistic avenues for clinical implementation focusing on low grade gliomas (LGG), high grade gliomas (HGG), management of the elderly patient with HGG, rare central nervous system tumors, craniospinal irradiation, and re-irradiation to examine how computational analysis and molecular science may synergistically drive advances in personalised radiation therapy (RT) and optimise patient outcomes.     

Synthesis and screening of an oroidin library against Pseudomonas aeruginosa biofilms

A 50-compound library based on the marine natural product oroidin was synthesized and assayed for anti-biofilm activity against PAO1 and PA14, two strains of the medically relevant gamma-proteobacterium Pseudomonas aeruginosa. Through structure-activity relationship (SAR) analysis of analogues based on the oroidin template, several conclusions can be drawn as to what structural properties of the synthetic derivatives are necessary to elicit a biological response. Notably, the most active analogues identified were those that contained a 2-aminoimidazole (2-AI) motif and a dibrominated pyrrolecarboxamide subunit. Here we disclose the synthesis and subsequently determined biological activity of this unique class of compounds as inhibitors of biofilm formation that have no direct antibiotic effect.     

Significance of Molecular Dynamics Simulations for Life Sciences

This article illustrates by examples the limited acceptance by biologists of predictions made with molecular dynamics simulations of biomolecules. Its purpose is to increase the awareness of biologists of the contribution that simulations can make to our understanding of biomolecule function.     

Phosphonate as a Stable Zinc-Binding Group for “Pathoblocker” Inhibitors of Clostridial Collagenase H (ColH)

Microbial infections are a significant threat to public health, and resistance is on the rise, so new antibiotics with novel modes of action are urgently needed. The extracellular zinc metalloprotease collagenase H (ColH) from Clostridium histolyticum is a virulence factor that catalyses tissue damage, leading to improved host invasion and colonisation. Besides the major role of ColH in pathogenicity, its extracellular localisation makes it a highly attractive target for the development of new antivirulence agents. Previously, we had found that a highly selective and potent thiol prodrug (with a hydrolytically cleavable thiocarbamate unit) provided efficient ColH inhibition. We now report the synthesis and biological evaluation of a range of zinc-binding group (ZBG) variants of this thiol-derived inhibitor, with the mercapto unit being replaced by other zinc ligands. Among these, an analogue with a phosphonate motif as ZBG showed promising activity against ColH, an improved selectivity profile, and significantly higher stability than the thiol reference compound, thus making it an attractive candidate for future drug development.     

三次致孔法制备类沸石分子筛的研究

本研究以山东粉煤灰(FA_1)、房山粉煤灰(FA_2)及黑龙江粉煤灰(FA_3)为原料,采用三次致孔法水热晶化合成类沸石分子筛,并研究了三次致孔法处理粉煤灰的晶型转化和颗粒团聚变化.并采用X射线衍射(XRD)、扫描电子显微镜(SEM)和X荧光法(XRF)进行检测.结果表明,以20％ HCl、液固比(L/S)为10的活化条件处理FA_1,得到物相单一且表面结构稳定的晶体;10 mol/L NaOH的改性条件下,进一步得到结晶良好的团聚体;晶化条件:硅铝物质的量比(Si/Al)为7.9,晶化温度为140℃,晶化时间为8h,制备出对苯蒸气吸附率为63.72％的类沸石分子筛.     

超高分子质量聚乙烯纤维黏结强度增强方法研究

为提高超高分子质量聚乙烯(UHMWPE)纤维复合材料中纤维与树脂基体之间的界面黏结强度,提出通过不同质量分数的硅烷偶联剂KH-570处理纳米SiO_2对UHMWPE纤维进行表面改性。对改性处理后的纤维与乙烯基酯树脂进行黏结强度试验,发现硅烷偶联剂处理纳米SiO_2能有效提高纤维的界面黏结强度,同时使纤维保持一定的断裂强度。     

New Organometallic Tetraphenylethylene⋅Iridium(III) Complexes with Antineoplastic Activity

Iridium(III) complexes have attracted more and more attention in the past few years because of their potential antineoplastic activity. In this study, four Ir^III complexes of the types [(η⁵-Cp^x)Ir(N^N)Cl]PF₆ (complexes 1 and 2 ) and [Ir(Phpy)₂(N^N)]PF₆ (complexes 3 and 4 ) have been synthesized and characterized. They exhibit potential antineoplastic activity towards A549 cells, especially in the case of complex 1 [IC₅₀=(3.56±0.5) μm ], which was nearly six times as effective as cisplatin [(21.31±1.7) μm ]. Additionally, these complexes show some selectivity towards cancer cells over normal cells. They could be transported by serum albumin (binding constants were changed from 0.37×10⁵ to 81.71×10⁵ m ⁻¹). Ir^III complexes 1 and 2 could catalyze the transformation of nicotinamide adenine dinucleotide reduced form (NADH) into NAD⁺ (turnover numbers 43.2, 11.9] and induce the accumulation of reactive oxygen species, thus confirming their antineoplastic mechanism of oxidation, whereas the cyclometalated complexes 3 and 4 were able to target the lysosome [Pearson co-localization coefficient (PCC)=0.73], cause lysosomal damage, and induce apoptosis. Understanding the mechanism of action would help further structure–activity optimization on these Ir^III complexes as emerging cancer therapeutics.     

Prediction of Polymer Properties in LDPE Reactors

Summary: A new analysis tool is presented that uses the governing kinetic scheme to predict properties of low‐density polyethylene (LDPE) such as the detailed shape of the molecular weight distribution (MWD). A model that captures mixing details of autoclave reactor operation is used to provide a new criterion for the onset of MWD shouldering. Kinetic effects are shown to govern the existence of MWD shoulders in LDPE reactors, even when operation is far from perfectly‐mixed. MWD shoulders occur when the mean reaction environment has a relatively high radical concentration and has a high polymer content, and is at a low temperature. Such conditions maximize long chain formation by polymer transfer and combination‐termination, while limiting chain scission. For imperfectly‐mixed reactors, the blending of polymer‐distributions produced in different spatial locations has a small effect on the composite MWD. However, for adiabatic LDPE autoclaves, imperfect mixing broadens the stable range of mean reactor conditions, and thereby increases the possibility for MWD shouldering.

Polymer MWD produced in an LDPE autoclave reactor by various kinetic mechanisms.     

A Systematic Structure–Activity Study of a New Type of Small Peptidic Transfection Vector Reveals the Importance of a Special Oxo-Anion-Binding Motif for Gene Delivery

We discovered a new class of artificial peptidic transfection vectors based on an artificial anion-binding motif, the guanidiniocarbonylpyrrole (GCP) cation. This new type of vector is surprisingly smaller than traditional systems, and our previous work suggested that the GCP group was important for promoting critical endosomal escape. We now present here a systematic comparison of similar DNA ligands featuring our GCP oxo-anion-binding motif with DNA ligands only consisting of naturally occurring amino acids. Structure–activity studies showed that the artificial binding motif clearly outperformed natural amino acids such as histidine, lysine, and arginine. It improved the ability to shuttle foreign genetic material into cells, yet successfully mediated endosomal escape. Also, plasmids that were complexed by our artificial ligands were stabilized against cytosolic degradation to some extent. This resulted in the successful expression of plasmid information (comparable to gold standards such as polyethyleneimine). Hence, our study clearly demonstrates the importance of the tailor-made GCP anion-binding site for efficient gene transfection.     

Electronic Properties and Molecular Simulations of Polyoxometalates

Taking classical polyoxometalates such as Lindqvist, Keggin, Dawson, and Preyssler anions as the starting point, a walk is taken through the electronic and structural properties of polyoxoanions in solution. We will discuss nucleation mechanisms, redox properties, and isomerism of polyoxometalates. The effects of confinement on water molecules and cation distributions inside nanocapsules are other topics discussed in the present review.     

Optimization of Drug Candidates That Inhibit the D-Loop Activity of RAD51

RAD51 is the central protein in homologous recombination (HR) repair, where it first binds ssDNA and then catalyzes strand invasion via a D-loop intermediate. Additionally, RAD51 plays a role in faithful DNA replication by protecting stalled replication forks; this requires RAD51 to bind DNA but may not require the strand invasion activity of RAD51. We previously described a small-molecule inhibitor of RAD51 named RI(dl)-2 (RAD51 inhibitor of D-loop formation #2, hereafter called 2 h ), which inhibits D-loop activity while sparing ssDNA binding. However, 2 h is limited in its ability to inhibit HR in vivo, preventing only about 50 % of total HR events in cells. We sought to improve upon this by performing a structure–activity relationship (SAR) campaign for more potent analogues of 2 h . Most compounds were prepared from 1-(2-aminophenyl)pyrroles by forming the quinoxaline moiety either by condensation with aldehydes, then dehydrogenation of the resulting 4,5-dihydro intermediates, or by condensation with N,N′-carbonyldiimidazole, chlorination, and installation of the 4-substituent through Suzuki–Miyaura coupling. Many analogues exhibited enhanced activity against human RAD51, but in several of these compounds the increased inhibition was due to the introduction of dsDNA intercalation activity. We developed a sensitive assay to measure dsDNA intercalation, and identified two analogues of 2 h that promote complete HR inhibition in cells while exerting minimal intercalation activity.