3-甲基-1-苯基-4-{4-（[5-甲基-2-（4-取代芳基）-嗯唑-4-基]甲氧基）-芳亚甲（苄）基}-2-吡唑啉-5-酮的设计、合成与降血糖活性

设计合成了具有降血糖活性的3-甲基-1-苯基4-[4-[[5-甲基-2-（4-取代芳基）-嗯唑4-基]甲氧基]-芳亚甲（苄）基]}-2-吡唑啉-5-酮类化合物．用丁二酮单肟和（取代的）苯甲醛环合、氯化得到氯甲基嗯唑衍生物，与对羟基苯甲醛或香兰醛缩合，再与3-甲基-1-苯基-2-吡唑啉-5-酮进行Knoevenagel反应及催化氢化得到目标化合物（Ⅰ和Ⅱ），共合成了16个未见文献报道的新化合物，并利用元素分析、IR、MS和^1H NMR确证了化合物的结构．初步药理试验结果表明，所合成的化合物有抑制血糖升高的倾向以及能明显加强和延长外源性胰岛素的降血糖作用，其中化合物Ib，Id和If尤为突出，说明这类化合物可能有增强胰岛素敏感性的作用．     

A mathematical model of insulin resistance in Parkinson’s disease

This paper introduces a mathematical model representing the biochemical interactions between insulin signaling and Parkinson’s disease. The model can be used to examine the changes that occur over the course of the disease as well as identify which processes would be the most effective targets for treatment. The model is mathematized using biochemical systems theory (BST). It incorporates a treatment strategy that includes several experimental drugs along with current treatments. In the past, BST models of neurodegeneration have used power law analysis and simulation (PLAS) to model the system. This paper recommends the use of MATLAB instead. MATLAB allows for more flexibility in both the model itself and in data analysis. Previous BST analyses of neurodegeneration began treatment at disease onset. As shown in this model, the outcomes of delayed, realistic treatment and full treatment at disease onset are significantly different. The delayed treatment strategy is an important development in BST modeling of neurodegeneration. It emphasizes the importance of early diagnosis, and allows for a more accurate representation of disease and treatment interactions.     

Pd–Porphyrin Oligomers Sensitized for Green‐to‐Blue Photon Upconversion: The More the Better?

A series of directly meso‐meso‐linked Pd–porphyrin oligomers (PdDTP‐M, PdDTP‐D, and PdDTP‐T) have been prepared. The absorption region and the light‐harvesting ability of the Pd–porphyrin oligomers are broadened and enhanced by increasing the number of Pd–porphyrin units. Triplet–triplet annihilation upconversion (TTA‐UC) systems were constructed by utilizing the Pd–porphyrin oligomers as the sensitizer and 9,10‐diphenylanthracene (DPA) as the acceptor in deaerated toluene and green‐to‐blue photon upconversion was observed upon excitation with a 532 nm laser. The triplet–triplet annihilation upconversion quantum efficiencies were found to be 6.2 %, 10.5 %, and 1.6 % for the [PdDTP‐M]/DPA, [PdDTP‐D]/DPA, and [PdDTP‐T]/DPA systems, respectively, under an excitation power density of 500 mW cm^?2. The photophysical processes of the TTA‐UC systems have been investigated in detail. The higher triplet–triplet annihilation upconversion quantum efficiency observed in the [PdDTP‐D]/DPA system can be rationalized by the enhanced light‐harvesting ability of PdDTP‐D at 532 nm. Under the same experimental conditions, the [PdDTP‐D]/DPA system produces more ³DPA* than the other two TTA‐UC systems, benefiting the triplet–triplet annihilation process. This work provides a useful way to develop efficient TTA‐UC systems with broad spectral response by using Pd–porphyrin oligomers as sensitizers.     

Panthogenins A and B,two novel norergostanol steroids from Dioscorea panthaica

Two novel 27-norergostanol steroids, panthogenins A （1） and B （2）, possessing unusual rings E and F featuring a ketal moiety at C-25 were isolated from rhizomes ofDioscorea panthaica. Their structures and relative configurations were elucidated by extensive spectroscopic methods including 1D and 2D NMR techniques, and the structure of panthogenin A was further confirmed by X-ray crystallography. Both compounds showed potent in vitro insulin sensitizing activity.     

Role of surface-exposed charged basic amino acids (Lys,Arg) and guanidination in insulin on the interaction and stability of insulin–insulin receptor complex

Naturally occurring proteins are emerging as novel therapeutics in the protein-based biopharmaceutical industry for the treatment of diabetes and obesity. However, proteins are not suitable for oral delivery due to short half-life, reduced physical and chemical stability and low permeability across the membrane. Chemical modification has been identified as a formulation strategy to enhance the stability and bioavailability of protein drugs. The present study aims to study the effect of charge-specific modification of basic amino acids (Lys, Arg) and guanidination on the interaction of insulin with its receptor using molecular modelling. Our investigation revealed that the guanidination of insulin (Lys-NHC = NHNH₂) enhanced and exerted stronger binding of the protein to its receptor through electrostatic interaction than native insulin (Lys-NH₃⁺). Point mutations of Lys and Arg (R22, K29; R22K, K29; R22, K29R; R22K, K29R) were attempted and the effects on the interaction and stability between insulin/modified insulins and insulin receptor were also analyzed in this study. The findings from the study are expected to provide a better understanding of the possible mechanism of action of the modified protein at a molecular level before advancing to real experiments.     

Benzimidazole/Pyridoimidazole‐Based Organic Sensitizers for High‐Performance Dye‐Sensitized Solar Cells

A new series of benzimidazole ( BIm )‐based dyes ( SC32 and SC33 ) and pyridoimidazole‐( PIm ) based dyes ( SC35, SC36N and SC36 ) were synthesized as sensitizers for dye‐sensitized solar cells (DSSCs). The N‐substituent and C‐substituent at the BIm and PIm cores were found to be the dominating factor in determining the electronic properties of the dyes and their DSSCs performance. The efficiency of BIm ‐based dyes ( SC35 and SC36 ) was found to be higher than that of the PIm ‐based dyes ( SC32 and SC33 ) due to better light harvesting. The C‐substituents in SC36 , a 4‐hexylloxybenzene and a hexyl chain, are beneficial to dark current suppression, and hence SC36 achieves the best efficiency of 7.38 % (≈85 % of N719 ). The two BIm dyes have better cell efficiencies than their congeners with a bithiophene entity between the BIm and the anchor due to better light harvesting of the former.     

Bis(phenothiazyl‐ethynylene)‐Based Organic Dyes Containing Di‐Anchoring Groups with Efficiency Comparable to N719 for Dye‐Sensitized Solar Cells

A new series of acetylene‐bridged phenothiazine‐based di‐anchoring dyes have been synthesized, fully characterized, and used as the photoactive layer for the fabrication of conventional dye‐sensitized solar cells (DSSCs). Tuning of their photophysical and electrochemical properties using different π‐conjugated aromatic rings as the central bridges has been demonstrated. This molecular design strategy successfully inhibits the undesirable charge recombination and prolongs the electron lifetime significantly to improve the power conversion efficiency (η ), which was proven by the detailed studies of electrochemical impedance spectroscopy (EIS) and open‐circuit voltage decay (OCVD). Under a standard air mass (AM) 1.5 irradiation (100 mW cm⁻²), the DSSC based on the dye with phenyl bridging unit exhibits the highest η of 7.44 % with open‐circuit photovoltage (V _oc) of 0.796 V, short‐circuit photocurrent density (J _sc) of 12.49 mA cm⁻² and fill factor (ff) of 0.748. This η value is comparable to that of the benchmark N719 under the same conditions.     

Modification of D–A–π–A Configuration toward a High‐Performance Triphenylamine‐Based Sensitizer for Dye‐Sensitized Solar Cells: A Theoretical Investigation

In an attempt to shed light on how the addition of a benzothiadiazole (BTD) moiety influences the properties of dyes, a series of newly designed triphenylamine‐based sensitizers incorporating a BTD unit as an additional electron‐withdrawing group in a specific donor–acceptor–π‐acceptor architecture has been investigated. We found that different positions of the BTD unit provided significantly different responses for light absorption. Among these, it was established that the further the BTD unit is away from the donor part, the broader the absorption spectra, which is an observation that can be applied to improve light‐harvesting ability. However, when the BTD unit is connected to the anchoring group a faster, unfavorable charge recombination takes place; therefore, a thiophene unit was inserted between these two acceptors, providing redshifted absorption spectra as well as blocking unfavorable charge recombination. The results of our calculations provide valuable information and illustrate the potential benefits of using computation‐aided sensitizer design prior to further experimental synthesis.