Biocatalytically oligomerized epicatechin with potent and specific anti-proliferative activity for human breast cancer cells

Catechins, naturally occurring flavonoids derived from wine and green tea, are known to exhibit multiple health benefits. Epigallocatechin gallate (EGCG) is one of the most widely investigated catechins, but its efficacy in cancer therapy is still inconsistent and limited. The poor stability of EGCG has contributed to the disparity in the reported anti-cancer activity and other beneficial properties. Here we report an innovative enzymatic strategy for the oligomerization of catechins (specifically epicatechin) that yields stable, water-soluble oligomerized epicatechins with enhanced and highly specific anti-proliferative activity for human breast cancer cells. This one-pot oxidative oligomerization is carried out in ambient conditions using Horseradish Peroxidase (HRP) as a catalyst yielding water-soluble oligo(epicatechins). The oligomerized epicatechins obtained exhibit excellent growth inhibitory effects against human breast cancer cells with greater specificity towards growth-inhibiting cancer cells as opposed to normal cells, achieving a high therapeutic differential. Our studies indicate that water-soluble oligomeric epicatechins surpass EGCG in stability, selectivity and efficacy at lower doses.     

Barrel- and crown-shaped dodecanuclear copper(II) cages built from phosphonate, pyrazole, and hydroxide ligands

The reaction of Cu(ClO4)2. 6H2O with t-BuP(O)(OH)2 and 3,5-(CF3)2PzH in the presence of triethylamine afforded the dodecanuclear cage ([Et3NH]2[Cu12(mu-3,5-(CF3)2Pz)6(mu3-OH)6(mu-OH)3(mu3-t-BuPO3)2(mu6-t-BuPO3)3][t-BuPO2OH][C6H5CH3]2) (2). The molecular structure of this cage revealed that it possesses a barrel-shaped architechture. The cage structure is built by the cumulative coordination action of phosphonate, hydroxide, and pyrazolyl ligands. A similar reaction involving Cu(NO3)2. 3H2O, t-BuP(O)(OH)2, 3,5-dimethylpyrazole, and triethylamine afforded another dodecanuclear cage [Cu12(mu-DMPz)8(eta1-DMPzH)2(mu4-O)2(mu3-OH)4(mu3- t-BuPO3)4].3MeOH (3). The latter is crown-shaped and is built by the coordination of pyrazole, pyrazolyl, phosphonate, hydroxide, oxide, and methanol ligands. Both of the dodecanuclear cages are efficient nucleases in the presence of magnesium monoperoxyphthalate.     

High-Performance Organic Field-effect Transistors from Functionalized Zinc Meso-Porphyrins

A series of new zinc porphyrins were synthesized, and their charge transport property was tuned by introducing various groups. Triarylamine was introduced to the porphyrin moiety at the meso-position as an electron donor, enhancing the charge carrier mobility. All the synthesized zinc porphyrins are thermally stable with a decomposition temperature over 178 °C. High frontier molecular orbitals levels of these compounds make them stable donor materials. SEM analysis of zinc porphyrins fabricated by spin-coating resulted in diversely self-assembled films. Field-effect transistors were fabricated using bottom-gate/top-contact architecture (BGTC) by solution-processable technique. The higher charge carrier mobility of 5.17 cm²/Vs with on/off of 10⁶ was obtained for trifluoromethyl substituted compound due to better molecular packing. In addition, GIXRD analysis revealed zinc porphyrins films crystalline nature, which supports its better charge carrier mobility. The present investigation has validated that zinc porphyrin building blocks are an attractive candidate for p-channel OFET devices.     

Microfluidic integration of substantially round glass capillaries for lateral patch clamping on chip

High-throughput screening of drug candidates for channelopathies can greatly benefit from an automated patch-clamping assay. Automation of the patch clamping through microfluidics ideally requires on-chip integration of glass capillaries with substantially round cross section. Such round capillaries, if they can only be integrated to connect isolated reservoirs on a substrate surface, will lead to a "lateral" configuration which is simple yet powerful for the patch clamping. We demonstrate here "lateral" patch clamping through microfluidic integration of substantially round glass capillaries in a novel process. The process adopts two well-known phenomena from microelectronics: keyhole-void formation and thermal-reflow of phosphosilicate glass in silicon trenches. The process relies on the same physical principle as the preparation of conventional micropipette electrodes by heat-pulling and fire-polishing glass tubes. The optimized process forms capillaries with a diameter approximately 1.5 microm and variation <10%. Functionality of the integrated glass capillaries for the patch-clamp recording has been verified by statistical test results from a sample of one hundred capillaries on mammalian cells (RBL-1) in suspension: 61% formed gigaseals (>1 GOmega) and of those approximately 48% (29% of all) achieved whole-cell recordings. Pharmacological blockade of ion channel activity and longevity of a whole-cell mode on these capillaries have also been presented.     

1 Pi<--X1 Sigma+ band systems of jet-cooled ScCo and YCo

Rotationally resolved resonant two-photon ionization (R2PI) spectra of ScCo and YCo are reported. The measured spectra reveal that these molecules possess ground electronic states of (1)Sigma(+) symmetry, as previously found in the isoelectronic Cr(2) and CrMo molecules. The ground state rotational constants for ScCo and YCo are B(0)(")=0.201 31(22) cm(-1) and B(0) (")=0.120 96(10) cm(-1), corresponding to ground state bond lengths of r(0) (")=1.812 1(10) A and r(0) (")=1.983 0(8) A, respectively. A single electronic band system, assigned as a (1)Pi<--X (1)Sigma(+) transition, has been identified in both molecules. In ScCo, the (1)Pi state is characterized by T(0)=15,428.8, omega(e)(')=246.7, and omega(e)(')x(e)(')=0.73 cm(-1). In YCo, the (1)Pi state has T(0)=13 951.3, omega(e)(')=231.3, and omega(e)(')x(e) (')=2.27 cm(-1). For YCo, hot bands originating from levels up to v(")=3 are observed, allowing the ground state vibrational constants omega(e)(")=369.8, omega(e)(")x(e)(")=1.47, and Delta G(12)(")=365.7 cm(-1) to be deduced. The bond energy of ScCo has been measured as 2.45 eV from the onset of predissociation in a congested vibronic spectrum. A comparison of the chemical bonding in these molecules to related molecules is presented.     

A new entry to polycyclic indole derivatives via intramolecular imino Diels-Alder reaction: observation of unexpected reaction

A new, efficient, and highly diastereoselective synthesis of polycyclic indole derivatives through intramolecular imino Diels-Alder reaction of aminoanthraquinone with N-prenylated indole-2-carboxaldehydes in the presence of 20 mol % of triphenylphosphonium perchlorate (TPPP) is reported with extremely high cis selectivity in good yield.     

Charge transfer states in the photophysics and photochemistry of polyimides and related phthalimides

Polyimides such as 6F-6F and 6F-ODA and model N-arylphthalimides are stabilized against photooxidative degradation by their electron donor (D) – acceptor (A) character. We have investigated the precise origin(s) of this effect using D and A substituents on the N-aryl groups of these compounds. The lowest excited singlet state (S₁) of N-arylphthalimides is an intramolecular charge transfer (ICT) state. A nominally twisted compound, N-(2-t-butylphenyl)phthalimide, shows greatly diminished CT absorption and blue-shifted fluorescence with reduced quantum yield when compared to the 4-t-butyl isomer with an identical N-aryl donor group. It therefore seems unnecessary to claim that the ICT state of phthalimides is a so-called TICT state. Quantum yield and fluorescence lifetime measurements lead to the conclusion that enhanced internal conversion from the ICT state (S₁) to the ground state makes a significant contribution to photostabilization of these compounds by suppressing formation of the reactive triplet state. Further stabilization of polymer films may be afforded by triplet state self-quenching which is enhanced for 6F-ODA in increasingly poor solvents. N-alkylarylphthalimides in which the aryl and phthalimide groups are not formally conjugated but, rather, joined by flexible methylene ‘spacers’, exhibit a different kind of fluorescent intramolecular CT singlet state whose formation can also stabilize these compounds by suppressing triplet state formation.     

Theoretical analysis of somatostatin receptor 5 with antagonists and agonists for the treatment of neuroendocrine tumors

We report on SSTR5 receptor modeling and its interaction with reported antagonist and agonist molecules. Modeling of the SSTR5 receptor was carried out using multiple templates with the aim of improving the precision of the generated models. The selective SSTR5 antagonists, agonists and native somatostatin SRIF-14 were employed to propose the binding site of SSTR5 and to identify the critical residues involved in the interaction of the receptor with other molecules. Residues Q2.63, D3.32, Q3.36, C186, Y7.34 and Y7.42 were found to be highly significant for their strong interaction with the receptor. SSTR5 antagonists were utilized to perform a 3D quantitative structure–activity relationship study. A comparative molecular field analysis (CoMFA) was conducted using two different alignment schemes, namely the ligand-based and receptor-based alignment methods. The best statistical results were obtained for ligand-based (\({q}^{2} = 0.454\), \({r}^{2}\) = 0.988, noc = 4) and receptor-guided methods (docked mode 1:\({q}^{2} = 0.530\), \({r}^{2} = 0.916\), noc = 5), (docked mode 2:\({q}^{2}\) = 0.555, \({r}^{2 }= 0.957\), noc = 5). Based on CoMFA contour maps, an electropositive substitution at \(\hbox {R}^{1}\), \(\hbox {R}^{2}\) and \(\hbox {R}^{4}\) position and bulky group at \(\hbox {R}^{4}\) position are important in enhancing molecular activity.     

苝类化合物研究与应用

苝类化合物具有大的共轭体系,易于进行结构修饰,可引入各种功能性基团,这种奇特结构赋予了苝类化合物优良的理化性质和特殊功能,在材料科学、超分子化学、生物、药学、医学等领域具有宽广的应用潜力,尤其在苝类有机光电材料已得到广泛的研究,取得了许多重要成就。尤其是近来越来越多的研究致力于开发苝类化合物其它可能的应用,已延伸到诸多领域,特别是相关生物医药的应用研究已成为近几年来异常活跃的新兴研究领域,引起广泛关注,进展迅速。本文结合课题组的研究工作,参考国内外近五年文献,首次系统地综述了苝类化合物在有机光电材料、纳米材料、生物医药光敏剂、生物荧光标记和成像、药物载体、人工诊断剂、人工离子受体和荧光分子探针等材料、生物、医药领域应用研究新进展。文中注重强化了化合物结构对苝类化合物性质和应用的影响。对未来苝类化合物研究与应用的发展趋势作了展望。