A Golgi-Targeted Platinum Complex Plays a Dual Role in Autophagy Regulation for Highly Efficient Cancer Therapy.

Regulating autophagy to control the homeostatic recycling process of cancer cells is a promising anticancer strategy. Golgi apparatus is a substrate of autophagy but the Golgi-autophagy (Golgiphagy) mediated antitumor pathway is rarely reported. Herein, we have developed a novel Golgi-targeted platinum (II) complex Pt3, which is ca. 20 times more cytotoxic to lung carcinoma than cisplatin and can completely eliminate tumors after intratumoral administration in vivo. Its nano-encapsulated system for tail vein administration also features a good anti-tumor effect. Mechanism studies indicate that Pt3 induces substantial Golgi stress, indicated by the fragmentation of Golgi structure, down-regulation of Golgi proteins (GM130, GRASP65/55), loss of Golgi-dependent transport and glycosylation. This triggers Golgiphagy but blocks the subsequent fusion of autophagosomes with lysosomes, that is a dual role in autophagy regulation, resulting in loss of proteostasis and apoptotic cell death. As far as we know, Pt3 is the first Golgi-targeted Pt complex that can trigger Golgi stress-mediated dual-regulation of autophagic flux and autophagy-apoptosis crosstalk for highly efficient cancer therapy.

Solution structure of a thrombin binding aptamer complex with a non-planar platinum(ii) compound.

Thrombin Binding Aptamer (TBA) is a monomolecular well-defined two G-tetrad antiparallel G-quadruplex DNA that inhibits the activity of human α-thrombin. In this report, we synthesized a quasi-cross-shaped platinum(ii) compound (L'2LPt) with one cyclometalated and two carbene ligands. We found L'2LPt has selective affinity to bind the TBA G-quadruplex. A fibrinogen clotting assay revealed that L'2LPt can abrogate the inhibitory activity of TBA against thrombin. We solved the 1 : 1 L'2LPt-TBA complex structure by NMR, which revealed a unique self-adaptive property of L'2LPt upon binding to TBA. In the complex, a carbene ligand of L'2LPt rotates to pair with the cyclometalated ligand to form a plane stacking over half of the TBA G-tetrad and covered by lateral TT loops. It is notable that the heavy atom Pt stays out of the G-tetrad. Meanwhile, the other carbene ligand remains relatively perpendicular and forms a hydrogen bond with a guanine to anchor the L'2LPt position. This structure exhibits a quasi-cross-shaped Pt(ii) compound bound to the G-quadruplex with an unusual "wall-mounted" binding mode. Our structures provide insights into the specific recognition of antiparallel G-quadruplex DNA by a self-adaptive Pt(ii) compound and useful information for the design of selective G-quadruplex targeting non-planar molecules.

Buchwald-Hartwig amination of aryl esters and chlorides catalyzed by the dianisole-decorated Pd-NHC complex.

A modular and generic method for the Buchwald-Hartwig amination reactions of relatively unreactive aryl esters as acyl electrophiles and aryl chlorides as aryl electrophiles has been developed, leading to the efficient synthesis of amides/amines under air conditions and with low catalyst loadings. The success of this catalytic protocol is mainly attributed to the modification of the Pd-IPr skeleton with sterically hindered and electron-donating anisole groups. This method also features good functional group tolerance and excellent chemoselectivities. In summary, the results presented herein suggest the possibility of developing a versatile and general protocol for diverse electrophiles to undergo the Buchwald-Hartwig amination reactions, avoiding too much consideration of the reaction conditions for the substrate-dependent C-N bond formations.

Selectivity and Targeting of G-Quadruplex Binders Activated by Adaptive Binding and Controlled by Chemical Kinetics.

G-quadruplexes (G4s) are prevalent in oncogenes and are potential antitumor drug targets. However, binding selectivity of compounds to G4s still faces challenges. Herein, we report a platinum(II) complex (Pt1), whose affinity to G4-DNA is activated by adaptive binding and selectivity controlled by binding kinetics. The resolved structure of Pt1/VEGF-G4 (a promoter G4) shows that Pt1 matches 3'-G-tetrad of VEGF-G4 through Cl- -dissociation and loop rearrangement of VEGF-G4. Binding rate constants are determined by coordination bond breakage/formation, correlating fully with affinities. The selective rate-determining binding step, Cl- -dissociation upon G4-binding, is 2-3 orders of magnitude higher than dsDNA. Pt1 potently targets G4 in living cells, effectively represses VEGF expression, and inhibits vascular growth in zebrafish. We show adaptive G4-binding activation and controlled by kinetics, providing a complementary design principle for compounds targeting G4 or similar biomolecules.

Synthesis of Pyrrolo[2,1,5-cd]indolizine Rings via Visible-Light-Induced Intermolecular [3+2] Cycloaddition of Indolizines and Alkynes.

A range of indolizine smoothly underwent visible-light-induced intermolecular [3+2] annulations with internal alkynes to afford pyrrolo[2,1,5-cd]indolizine in good to excellent yields with high regioselectivity. Through this cascade reaction, a series of fluoroactive fused indolizines with a large π-system were conveniently synthesized. The usage of visible light as energy source with air as a stoichiometric oxidant under simple conditions makes this process attractive and practical.

cis-{1-Butyl-3-[2-(phenyl-sulfan-yl)eth-yl]-4-imidazolin-2-yl-κ2 C 2,S'}di-chlorido-platinum(II).

The asymmetric unit of the title compound, [PtCl2(C15H20N2S)], comprises one PtII ion, one N-heterocyclic carbene(NHC)-thio-ether ligand and two chloride ions. The PtII ion is four-coordinated by one C atom and one S atom of the NHC-thio-ether ligand, and by two chloride ions, forming an approximately square-planar geometry. In the crystal, the mol-ecules are linked via C-H⋯Cl and C-H⋯π inter-actions, forming a layer parallel to the ab plane.

Highly Regioselective, Acid-Catalyzed, Three-Component Cascade Reaction for the Synthesis of 2-aminopyridine-Decorated Imidazo[1,2- a]pyridine.

A highly regioselective acid-catalyzed three-component reaction of 2-aminopyridine and 3-phenylpropiolaldehyde for the construction of imidazo[1,2- a]pyridine has been developed. This strategy provides a broad range of substrates and represents an efficient approach to give various 2-aminopyridine-decorated imidazo[1,2- a]pyridine in good yields.

Dipotassium tetra-aqua-bis-(µ-citrato-κ(4) O:O',O'',O''')nickelate(II) tetra-hydrate.

The title complex, K2[Ni2(C6H5O7)2(H2O)4]·4H2O, is a dinuclear centrosymmetric anionic octa-hedral complex, involv-ing citrates as tridentate and bridging ligands, and coordinating water mol-ecules. An extensive network of hydrogen bonds connects the complex anions through the two unique uncoordinating water mol-ecules. The K(+) counter cation is surrounded by seven O atoms in the form of an irregular polyhedron and further stabilizes the crystal packing.

Dichlorido[1-(2,6-dimethyl-phenyl-imino)-1,2-diphenyl-propan-2-ol-κN,O]palladium(II) methanol monosolvate.

The title compound, [PdCl(2)(C(23)H(23)NO)]·CH(3)OH, was obtained by the reaction of 1-(2,6-dimethyl-phenyl-imino)-1,2-diphenyl-propan-2-ol and palladium chloride in methanol. The Pd atom is four-coordinated by the O atom of a tertiary alcohol, the imine N atom of the hy-droxy-limine part of the bidentate ligand and by two chloride ions, forming a nearly square-planar geometry. The complex mol-ecule and the uncoordinated methanol mol-ecule are connected via an O-H⋯O hydrogen bond.

Copper-rich framework sulfides: A(4)Cu(8)Ge(3)S(12) (A = K, Rb) with cubic perovskite structure.

Two copper-rich open-framework sulfides, K(4)Cu(8)Ge(3)S(12) (1) and Rb(4)Cu(8)Ge(3)S(12) (2), have been synthesized under solvothermal conditions. Compounds 1 and 2 are isostructural and contain icosahedral [Cu(8)S(12)](16-) clusters as basic building blocks. These clusters are primitive cubic packed and connect to one another by discrete Ge(4+) ions to generate 3D copper-rich Cu-Ge-S framework and form 3D channels along 100 directions where the alkali metal cations reside. These two open-framework sulfides crystallize in cubic perovskite structure.

(H(2)en)(2)Cu(8)Sn(3)S(12): a trigonal CuS(3)-based open-framework sulfide with interesting ion-exchange properties.

(H(2)en)(2)Cu(8)Sn(3)S(12) contains a trigonal CuS(3)-based framework into which Sn(4+) ions are incorporated, and exhibits multiple channel systems and interesting ion-exchange properties.

Syntheses and characterization of a series of silver-thioantimonates(III) and thioarsenates(III) containing two types of silver-sulfur chains.

Three framework silver-thioantimonates, K(3)Ag(9)Sb(4)S(12)(1), Rb(3)Ag(9)Sb(4)S(12)(2), and Cs(3)Ag(9)Sb(4)S(12)(3), and one layered silver-thioarsenate, CsAg(2)AsS(3)(4), have been synthesized solvothermally in the presence of thiophenol as a mineralizer. Compounds 1, 2, and 3 are isostructural and contain infinite silver-sulfur chains [Ag(9)S(12)](15-). These chains are connected to one another by the antimony atoms to generate wide channels along the [001] direction where the alkali metal cations reside. The structure of 4 consists of helical chains [Ag(2)S(3)](4-) linked by the arsenic atoms to form layers with potassium ions between the layers.

New framework iodoargentates: M(en)3Ag2I4 (M=Zn, Ni) with tridymite topology.

Two novel framework compounds, Zn(en) 3Ag2I4 (1) and Ni(en) 3Ag2I4 (2), have been synthesized by a self-assembly reaction. Both of them contain an unexpected framework, Ag2I4(2-) with tridymite topology, and the discrete M(en)3(2+) cations are located in the channels. Their thermal properties and circular dichroism spectra were investigated.