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.     

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.     

Structural optimization of thiophene-(N-aryl)pyrrole-thiophene-based metal-free organic sensitizer for the enhanced dye-sensitized solar cell performance

In this study, we prepared thiophene-(N-aryl)pyrrole-thiophene (TPT)-based two new metal-free organic sensitizers (TPTDYE 2 and TPTDYE 3) with the aim of improving the dye-sensitized solar cell (DSSC) performance of recently reported TPT-based organic sensitizer (TPTDYE 1). The molecular structure of TPTDYE 1 was tuned by decreasing the distance between the donor and acceptor groups (TPTDYE 2) or by introducing a fluoride atom on the phenyl ring near to the electron accepting cyanoacrylic acid group (TPTDYE 3). The photophysical and electrochemical studies of the newly synthesized sensitizers revealed that their absorption and energy levels were significantly altered compared to those of TPTDYE 1. The DSSC performance of each of sensitizers TPTDYE 2 and TPTDYE 3 was investigated with and without coadsorbent and compared with those of TPTDYE 1 and standard N719. Between the two DSSCs, the one sensitized by TPTDYE 2 offered greatly improved solar to electrical energy conversion efficiency of 6.85% without coadsorbent and 7.06% with coadsorbent. The overall conversion efficiency of the DSSC sensitized by TPTDYE 2 without and with coadsorbent was found to be improved by 32% and 20%, respectively, compared with that of the DSSC sensitized by TPTDYE 1 and almost equal (98.7%) to that of the standard cell prepared from N719 under an identical condition.     

Restricted Rotation of σ‐Bonds through a Rigidified Donor Structure to Increase the ICT Ability of Platinum‐Acetylide‐Based DSSCs

A series of new triarylamine‐based platinum‐acetylide complexes ( WY s) have been designed and synthesized as new sensitizers for applications in dye‐sensitized solar cells (DSSCs). With the aim of investigating the effect of a rigidifying donor structure on the photoelectrical parameters of the corresponding DSSCs, two new sensitizers, WY1 and WY2 , with rigid and coplanar fluorene units as an electron donor, were prepared. Moreover, two sensitizers that contained triphenylamine units as an electron donor, WY3 and WY4 , were also synthesized for comparison. The photo‐ and electrochemical properties of all of these new complexes have been extensively explored. We found that the dimethyl‐fluorene unit exhibited a stronger electron‐donating ability and better photovoltaic performance compared to the triphenylamine unit, owing to its rigidifying structure, which restricted the rotation of σ bonds, thus increasing the conjugation efficiency. Furthermore, WY2 , which contained a dimethyl‐fluorene unit as an electron donor and bithiophene as a π bridge, showed a relatively high open‐circuit voltage (V_oc) of 640 mV and a PCE of 4.09 %. This work has not only expanded the choice of platinum‐acetylide sensitizers, but also demonstrates the advantages of restricted rotation of donor σ bonds for improved behavior of the corresponding DSSCs.     

Hydroxy-Porphyrin as an Effective,Endogenous Molecular Clamp during Early Stages of Amyloid Fibrillization

Amyloid fibril formation of proteins is of great concern in neurodegenerative disease and can be detrimental to the storage and stability of biologics. Recent evidence suggests that insulin fibril formation reduces the efficacy of type II diabetes management and may lead to several complications. To develop anti-amyloidogenic compounds of endogenous origin, we have utilized the hydrogen bond anchoring, π stacking ability of porphyrin, and investigated its role on the inhibition of insulin amyloid formation. We report that hydroxylation and metal removal from the heme moiety yields an excellent inhibitor of insulin fibril formation. Thioflavin T, tyrosine fluorescence, Circular Dichorism (CD) spectroscopy, Field emission scanning electron microscopy (FESEM) and molecular dynamics (MD) simulation studies suggest that hematoporphyrin (HP) having hydrogen bonding ability on both sides is a superior inhibitor compared to hemin and protoporphyrin (PP). Experiments with hen egg white lysozyme (HEWL) amyloid fibril formation also validated the efficacy of endogenous porphyrin based small molecules. Our results will help to decipher a general therapeutic strategy to counter amyloidogenesis.     

Binding Mode of Insulin Receptor and Agonist Peptide

LI Wei Introduction In1986,Geysen[1]foundthatshortpeptidescon tainingthekeyresiduesofaproteincanmimicthede terminantoftheprotein;mostofthebindingenergybe tweenproteinsresultsfromthenoncovalentinteractions ofsomekeyresidues.Thesesmallpeptidesgenerally have…