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.     

Assembling metal phosphonates in the presence of monodentate-terminal and bidentate-bridging pyridine ligands. Use of non-covalent and covalent-coordinate interactions to build polymeric metal-phosphonate architectures

The cubic transition metal phosphonates [(t)BuPO3M(2-apy)]4 (M= Zn (1), Co (2)), whose core resembles the D4R SBU of zeolites, have been synthesized from a reaction between the corresponding metal acetate, tert-butylphosphonic acid and 2-aminopyridine (2-apy) at room temperature. X-Ray structure determination reveals that the molecules of 1 and 2, which crystallize in the tetragonal I4(1)/a space group with crystallographically imposed 4 symmetry, form a 3-D supramolecular assembly aided by N-H...O hydrogen bonding. When the same reaction was carried out by using a bridging bidentate Lewis base such as 4,4'-bipyridine, insoluble precipitate is obtained for both zinc and cobalt. In the case of other metal salts such as copper, manganese and nickel, however, one-dimensional polymeric compounds such as [M((t)BuPO3H)2(4,4'-bipy)(H2O)2]n (M= Cu (3), Mn (4)), [(Ni(4,4'-bipy)(H2O)4)((t)BuPO3H)2(H2O)]n (5) have been isolated. The solid-state structures of 3-5 have been determined by single crystal X-ray diffraction studies. Compounds 3 and 4 are isostructural and crystallize in the triclinic P1 space group with two phosphonate ligands coordinated to the metal centers in a [1.100] fashion, whereas in the case of compound 5, the polymeric backbone is formed by Ni-4,4'-bipy units and the phosphonate anions show no bonding interaction to the metal. The 1-D polymeric chains of 3-5 organize in the solid-state as 3-D supramolecular assemblies with the aid of extensive hydrogen bonding interaction between coordinated water molecules and P-OH or P=O groups of the phosphonate ligands.     

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.     

Physical insights from a penetration depth model of optically pumped NMR

A model of optically pumped NMR (OPNMR) behavior in GaAs that connects the photon energy dependence of the OPNMR signal intensity for (69)Ga with different polarizations of light has been developed. Inputs to this model include experimental conditions--external magnetic field (B(0)), temperature (T), and optical pumping parameters (tau(L), laser helicity)--as well as parameters that arise from sample-specific characteristics--electron spin lifetime (T(1e)), electron lifetime (tau(e)), electron-nuclear correlation time (tau(c)), and sample thickness (z). These various inputs affect the profile of the OPNMR signal intensity as a function of photon energy (E) in a predictable manner. Therefore, the profile can serve as a composite fingerprint by which individual parameters can be inferred when not known. Characteristics of the profile include the photon energy for maximum OPNMR signal intensity and the intensity ratio between sigma(+) and sigma(-) light.     

Optically pumped nuclear magnetic resonance of semiconductors

Optically pumped NMR (OPNMR) of direct gap and indirect gap semiconductors has been an area of active research interest, motivated by both basic science and technological perspectives. Proposals to enhance and to spatially localize nuclear polarization have stimulated interest in this area. Recent progress in OPNMR has focused on exploring the experimental parameter space in order to elucidate details of the underlying photophysics of optical pumping phenomena. The focus of this review is on recent studies of bulk samples of GaAs and InP, namely, the photon energy dependence, the magnetic field dependence, and the phase dependence of OPNMR resonances. Models for the development of nuclear polarization are discussed.     

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.     

Unusual reactivity of a sterically hindered diphosphazane ligand, EtN{P(OR)(2)}(2), (R = C(6)H(3)(Pr(I))(2)-2,6) towards (eta(3)-allyl)palladium precursors

The reactivity of (eta(3)-allyl)palladium chloro dimers [(1-R-eta(3)-C(3)H(4))PdCl](2) (R = H or Me) towards a sterically hindered diphosphazane ligand [EtN{P(OR)(2)}(2)] (R = C(6)H(3)(Pr(i))(2)-2,6), has been investigated under different reaction conditions. When the reaction is carried out using NH(4)PF(6) as the halide scavenger, the cationic complex [(1-R-eta(3)-C(3)H(4))Pd{EtN(P(OR)(2))(2)}]PF(6) (R = H or Me) is formed as the sole product. In the absence of NH(4)PF(6), the initially formed cationic complex, [(eta(3)-C(3)H(5))Pd{EtN(P(OR)(2))(2)}]Cl, is transformed into a mixture of chloro bridged complexes over a period of 4 days. The dinuclear complexes, [(eta(3)-C(3)H(5))Pd(2)(mu-Cl)(2){P(O)(OR)(2)}{P(OR)(2)(NHEt)}] and [Pd(mu-Cl){P(O)(OR)(2)}{P(OR)(2)(NHEt)}](2) are formed by P-N bond hydrolysis, whereas the octa-palladium complex [(eta(3)-C(3)H(5))(2-Cl-eta(3)-C(3)H(4))Pd(4)(mu-Cl)(4)(mu-EtN{P(OR)(2)}(2))](2), is formed as a result of nucleophilic substitution by a chloride ligand at the central carbon of an allyl fragment. The reaction of [EtN{P(OR)(2)}(2)] with [(eta(3)-C(3)H(5))PdCl](2) in the presence of K(2)CO(3) yields a stable dinuclear (eta(3)-allyl)palladium(I) diphosphazane complex, [(eta(3)-C(3)H(5))[mu-EtN{P(OR)(2)}(2)Pd(2)Cl] which contains a coordinatively unsaturated T-shaped palladium center. This complex exhibits high catalytic activity and high TON's in the catalytic hydrophenylation of norbornene.     

Determination of 77Se-77Se and 77Se-13C J-coupling parameters for the clusters [Re5OsSe8(CN)6]3- and [Re4Os2Se8(CN)6]2-

We have investigated rarely observed 77Se J-couplings (spin-spin couplings) in the mixed-metal face-capped octahedral clusters [Re5OsSe8(CN)6]3- and [Re4Os2Se8(CN)6]2- at natural abundance. To the best of our knowledge, these are the first observations of Se-Se spin-spin interactions between mu3-Se sites, important for stereochemical assignments in hexarhenium analogues, Chevrel phase materials, and similar cluster materials. NMR techniques such as COSY, INADEQUATE, and 2D J-resolved spectroscopy have been used in conjunction to study these interactions. The two isomers (cis and trans) of [Re4Os2Se8(CN)6]2- were distinguishable, and selective isotopic labeling of [Re5OsSe8(CN)6]3- with 13CN ligands enabled resonances to be assigned by observing the 2J (Se-M-C) couplings. For [Re5OsSe8(CN)6]3-, two different 2J (Se-M-Se) couplings were measurable on a single cluster, and these are related to one another through spin-spin interactions across a face diagonal or along an edge of the cube of inner selenium ligands. A rigorous analysis based on combinatorial math has been invoked to assign the couplings on the basis of the probability of multiple-spin interactions. The face diagonal association is found to result in a J-coupling interaction larger in magnitude than that from coupling along an edge of the cube-information critical for making stereochemical assignments of selenium sites.