Synthesis and antioxidant evaluation of (S,S)- and (R,R)-secoisolariciresinol diglucosides (SDGs)

Secoisolariciresinol diglucosides (SDGs) (S,S)-SDG-1 (major isomer in flaxseed) and (R,R)-SDG-2 (minor isomer in flaxseed) were synthesized from vanillin via secoisolariciresinol (6) and glucosyl donor 7 through a concise route that involved chromatographic separation of diastereomeric diglucoside derivatives (S,S)-8 and (R,R)-9. Synthetic (S,S)-SDG-1 and (R,R)-SDG-2 exhibited potent antioxidant properties (EC₅₀ = 292.17 ± 27.71 μM and 331.94 ± 21.21 μM, respectively), which compared well with that of natural (S,S)-SDG-1 (EC₅₀ = 275.24 ± 13.15 μM). These values are significantly lower than those of ascorbic acid (EC₅₀ = 1129.32 ± 88.79 μM) and α-tocopherol (EC₅₀ = 944.62 ± 148.00 μM). Compounds (S,S)-SDG-1 and (R,R)-SDG-2 also demonstrated powerful scavenging activities against hydroxyl [natural (S,S)-SDG-1: 3.68 ± 0.27; synthetic (S,S)-SDG-1: 2.09 ± 0.16; synthetic (R,R)-SDG-2: 1.96 ± 0.27], peroxyl [natural (S,S)-SDG-1: 2.55 ± 0.11; synthetic (S,S)-SDG-1: 2.20 ± 0.10; synthetic (R,R)-SDG-2: 3.03 ± 0.04] and DPPH [natural (S,S)-SDG-1: EC₅₀ = 83.94 ± 2.80 μM; synthetic (S,S)-SDG-1: EC₅₀ = 157.54 ± 21.30 μM; synthetic (R,R)-SDG-2: EC₅₀ = 123.63 ± 8.67 μM] radicals. These results confirm previous studies with naturally occurring (S,S)-SDG-1 and establish both (S,S)-SDG-1 and (R,R)-SDG-2 as potent antioxidants and free radical scavengers for potential in vivo use.     

Synthesis and structures of heterodinuclear organoplatinum(or -palladium)–molybdenum(or -tungsten) complexes: Unexpected structural deformation of heterodinuclear propionylplatinum–tungsten complex having 1,2-bis(diphenylphosphino)ethane ligand

Synthesis of a series of heterodinuclear phenylpalladium–molybdenum(or -tungsten) complexes having a bidentate nitrogen ligand, L₂PhPd–MCp(CO)₃ (M = Mo, L₂ = tmeda (12), bpy (13), phen (14); M = W, L₂ = tmeda (15)) by metathetical reactions of PdPhIL₂ with Na[MCp(CO)₃] and acylplatinum–molybdenum(or -tungsten) complex having a 1,2-bis(diphenylphosphino)ethane ligand, (dppe)(RCO)Pt–MCp(CO)₃ (M = Mo, R = Et (16), CH₂CMe₃ (18); M = W, R = Et (17)) by CO insertion into Pt–C bond in corresponding alkyl analogues (dppe)RPt–MCp(CO)₃ (M = Mo, R = Et (6), CH₂CMe₃, M = W, R = Et (8)) are described. These complexes are characterized by NMR and IR spectroscopies and elemental analyses, and the molecular structures of 12, 13, 17 and 18 are determined by X-ray structure analysis. The geometry at Pt (or Pd) is square planar and the MCp(CO)₃ moiety has three-leg piano-stool geometries in these complex expect the propionylplatinum–tungsten complex 17, which shows apparent but unexpected structural deformation at Pt and W, giving twisted square-planar and four-leg piano-stool geometries for platinum and tungsten, respectively.     

Chiral porphyrin complexes of cobalt(II) and ruthenium(II) in catalytic cyclopropanation and amination reactions

We report here the syntheses of two new metal complexes (M = Co, 2; M = Ru, 3) of the chiral porphyrin TmyrtP (1) (TmyrtP = dianion of the meso-tetrakis[(1R)-apopinen-2-yl]porphyrin). Both complexes exist as a mixture of atropisomers. Complexes 2 and 3 activate aromatic azides for the amination under mild conditions of unsaturated hydrocarbons. Even though the observed ee values are low, this is the first asymmetric transfer of the nitrene residue of aryl azides to a prochiral olefin catalyzed by a transition metal complex to be reported in the literature. Complex 3 also showed a good catalytic activity in cyclopropanation reactions with ethyldiazoacetate even at low temperatures (−30 °C) but a poor diastereo- and enantioselectivity were observed.     

Evaluation of (Z)-2-((1-benzyl-1H-indol-3-yl)methylene)-quinuclidin-3-one analogues as novel,high affinity ligands for CB1 and CB2 cannabinoid receptors

A small library of N-benzyl indolequinuclidinone (IQD) analogs has been identified as a novel class of cannabinoid ligands. The affinity and selectivity of these IQDs for the two established cannabinoid receptor subtypes, CB1 and CB2, was evaluated. Compounds 8 (R = R² = H, R¹ = F) and 13 (R = COOCH₃, R¹ = R² = H) exhibited high affinity for CB2 receptors with K_i values of 1.33 and 2.50 nM, respectively, and had lower affinities for the CB1 receptor (K_i values of 9.23 and 85.7 nM, respectively). Compound 13 had the highest selectivity of all the compounds examined, and represents a potent cannabinoid ligand with 34-times greater selectivity for CB2R over CB1R. These findings are significant for future drug development, given recent reports demonstrating beneficial use of cannabinoid ligands in a wide variety of human disease states including drug abuse, depression, schizophrenia, inflammation, chronic pain, obesity, osteoporosis and cancer.     

New pentafluorophenyl complexes with phosphine-amide ligands

A series of nickel(II) and palladium(II) complexes containing one or two pentafluorophenyl ligands and the phosphino-amides o-Ph₂PC₆H₄CONHR [R = ⁱPr (a), Ph (b)] displaying different coordination modes have been synthesised. The chelating ability of these ligands and the influence of both coligands and the metal centre in their potential hemilabile behaviour have been explored. The crystal structure of (b) has been determined and reveals N–H⋯O intermolecular hydrogen bonding. Bis-pentafluorophenyl derivatives [M(C₆F₅)₂(o-Ph₂PC₆H₄CO-NHR)] [M = Ni; R = ⁱPr (1a); R = Ph (1b); M = Pd; R = ⁱPr (2a); R = Ph (2b)] in which (a) and (b) act as rigid P, O-chelating ligands were readily prepared from the labile precursors cis-[M(C₆F₅)₂(PhCN)₂]. X-ray structures of (1a), (1b) and (2a) have been established, allowing an interesting comparative structural discussion. Dinuclear [{Pd(C₆F₅)(tht)(μ-Cl)}₂] reacted with (a) and (b) yielding the monopentafluorophenyl complexes [Pd(C₆F₅)Cl{PPh₂(C₆H₄–CONH–R)}] (R = ⁱPr (3a), Ph (3b)) that showed a P, O-chelating behaviour of the ligands, confirmed by the crystal structure determination of (3a). New cationic palladium(II) complexes in which (a) and (b) behave as P-monodentate ligands have been synthesised by reacting them with [{Pd(C₆F₅)(tht)(μ-Cl)}₂], stoichiometric Ag(O₃SCF₃) and external chelating reagents such as cod [Pd(C₆F₅)(cod){PPh₂(C₆H₄-CONH-R)}](O₃SCF₃)(R = ⁱPr (4a), Ph (4b)) and 2,2′-bipy [Pd(C₆F₅)(bipy){PPh₂(C₆H₄-CONH-R)}](O₃SCF₃) (R = ⁱPr (5a), Ph (5b)). When chloride abstraction in [{Pd(C₆F₅)(tht)(μ-Cl)}₂] is promoted by means of a dithioanionic salt as dimethyl dithiophospate in the presence of (a) or (b), the corresponding neutral complexes [Pd(C₆F₅){S(S)P(OMe)₂}{PPh₂(C₆H₄-CONH-R)}] (R = ⁱPr (6a), Ph (6b)) were obtained.     

Structure and catalytic activity of rhodium(I) carbene complexes in polymerization of phenylacetylene

Rh(I) carbene complexes of [RhX(bmim)(η⁴-1,5-cod)] type (bmim = 1-butyl-3-methyl imidazolium cation, X = Cl 2, Br 3, I 4), obtained in the reaction of [Rh(OMe)(η⁴-1,5-cod)]₂ (1) with [bmim]X ionic liquids, catalyzed polymerization of phenylacetylene (PA) to cis-polyphenylacetylene (PPA) in CH₂Cl₂ and in ionic liquids. The yield of PPA increased and molecular weight (M_w) decreased after addition of phosphorus ligands PPh₃ or P(OPh)₃. Complex 4 reacted with P(OPh)₃ giving cis-[RhI(bmim)(P(OPh)₃)₂] (5) complex which catalyzed oligomerization but not polymerization of PA.     

Evaluation of the association of mercury(II) with some dicysteinyl tripeptides

The present study was undertaken to gain insight into the associations of mercury(II) with dicysteinyl tripeptides in buffered media at pH 7.4. We investigated the effects of increasing the distance between cysteinyl residues on mercury(II) associations and complex formations. The peptide–mercury(II) formation constants and their associated thermodynamic parameters in 3-(N-morpholino)propanesulfonic acid (MOPS) buffered solutions were evaluated by isothermal titration calorimetry. Complexes formed in different relative ratios of mercury(II) to cysteinyl peptides in ammonium formate buffered solutions were characterized by LTQ Orbitrap mass spectrometry. The results from these studies show that n-alkyl dicysteinyl peptides (CP 1–4), and an aryl dicysteinyl peptide (CP 5) can serve as effective “double anchors” to accommodate the coordination sites of mercury(II) to form predominantly one-to-one Hg(peptide) complexes. The aryl dicysteinyl peptide (CP 5) also forms the two-to-two Hg₂(peptide)₂ complex. In the presence of excess peptide, Hg(peptide)₂ complexes are also detected. Notably, increasing the distance between the ligating groups or “anchor points” in CP 1–5 does not significantly affect their affinity for mercury(II). However, the enthalpy change (ΔH) values (ΔH₁ ∼ −91 kJ mol⁻¹ and ΔH₂ ∼ −66 kJ mol⁻¹) for complex formation between CP 4 and 5 with mercury(II) are about one and a half times larger than the related values for CP 1, 2 and 3 (ΔH₁ ∼ −66 kJ mol⁻¹ and ΔH₂ ∼ 46 kJ mol⁻¹). The corresponding entropy change (ΔS) values (ΔS₁ ∼ −129 J K⁻¹ mol⁻¹ and ΔS₂ ∼ −116 J K⁻¹ mol⁻¹) of the structurally larger dicysteinyl peptides CP 4 and 5 are less entropically favorable than for CP 1, 2 and 3 (ΔS₁ ∼ −48 J K⁻¹ mol⁻¹ and ΔS₂ ∼ −44 J K⁻¹ mol⁻¹). Generally, these associations result in a decrease in entropy, indicating that these peptide–mercury complexes potentially form highly ordered structures. The results from this study show that dicysteinyl tripeptides are effective in binding mercury(II) and they are promising motifs for the design of multi-cysteinyl peptides for binding more than one mercury(II) ion per peptide.     

Synthesis,characterization, structure and luminescence studies of dinuclear gold(I) alkynyls of bis(diphenylphosphino)alkyl- and aryl-amines

A series of alkynylgold(I) bis(diphenylphosphino)alkyl- and aryl-amine complexes, [{Ph₂PN(R)PPh₂}Au₂(CCR′)₂] [R = ⁿPr, R′ = Ph (1), C₆H₄OMe-p (2), C₆H₄Me-p (3), C₆H₄Cl-p (4); R = C₆H₄OMe-p, R′ = Ph (5)], has been synthesized. The X-ray crystal structures of 1 and 2 revealed the presence of short intramolecular Au⋯Au contacts with the distances of 2.8404(8) and 3.0708(7) Å. The luminescence behavior of the complexes were studied.     

Copper(II) and zinc(II) complexes with Schiff-base ligands derived from salicylaldehyde and 3-methoxysalicylaldehyde: Synthesis,crystal structures,magnetic and luminescence properties

The following Schiff bases were employed as ligands in synthesizing copper(II) and zinc(II) complexes: N-[(2-pyridyl)-methyl]-salicylimine (Hsalampy), N-[2-(N,N-dimethyl-amino)-ethyl]-salicylimine (Hsaldmen), and N-[(2-pyridyl)-methyl]-3-methoxy-salicylimine (Hvalampy). The first two ligands were obtained by reacting salicylaldehyde with 2-aminomethyl-pyridyne and N,N-dimethylethylene diamine, respectively, while the third one results from the condensation of 3-methoxysalicylaldehyde with 2-aminomethyl-pyridine. Four new coordination compounds were synthesized and structurally characterized: [Cu(salampy)(H₂O)(ClO₄)] 1, [Cu₂(salampy)₂(H₂trim)₂] 2 (H₂trim^? = the monoanion of the trimescic acid), [Cu₄(valampy)₄](ClO₄)₄ · 2CH₃CN 3, and [Zn₃(saldmen)₃(OH)](ClO₄)₂ · 0.25H₂O 4. The crystal structure of 1 consists of supramolecular dimers resulted from hydrogen bond interactions established between mononuclear [Cu(salampy)(H₂O)(ClO₄)] complexes. Compound 2 is a binuclear complex with the copper ions connected by two monoatomic carboxylato bridges arising from two molecules of monodeprotonated trimesic acid. The crystal structure of 3 consists of tetranuclear cations with a heterocubane {Cu₄O₄} core, and perchlorate ions. Compound 4 is a trinuclear complex with a defective heterocubane structure. The magnetic properties of complexes 1–3 have been investigated. Compound 4 exhibits solid-state photoluminescence at room temperature.     

Synthesis,spectral and magnetical characterization of monomeric [Cu(2-NO2bz)2(3-pyme)2(H2O)2] and polymeric [Cu{3,5-(NO2)2bz}2(3-pyme)2]n

Two new complexes of composition [Cu(2-NO₂bz)₂(3-pyme)₂(H₂O)₂] (1) and/or [Cu{3,5-(NO₂)₂bz}₂(3-pyme)₂] (2) (3-pyme = 3-pyridylmethanol, ronicol or 3-pyridylcarbinol, 2-NO₂bz = 2-nitrobenzoate and 3,5-(NO₂)₂bz = 3,5-dinitrobenzoate) have been prepared and studied by elemental analysis, electronic, infrared and EPR spectroscopy, magnetic susceptibility measurements and the structure of both complexes has been solved. Complex (1) shows an unusual molecular type of structure consisting of the [Cu(2-NO₂bz)₂(3-pyme)₂(H₂O)₂] molecules held together by hydrogen bonds and van der Waals interactions. Complex (2) exhibits a polymeric chain-like structure [Cu{3,5-(NO₂)₂bz}₂(3-pyme)₂]_n with copper atoms doubly bridged by two 3-pyridylmethanol molecules and the polymeric molecules are held together by van der Waals interactions. Complex (1) exhibits a magnetic moment μ_eff = 1.84 B.M. at 300 K that remains nearly constant within the temperature region (5–300 K). Further cooling results in lowering the magnetic moment to μ_eff = 1.82 B.M. at 1.8 K. The magnetic susceptibility temperature dependence obeys Curie–Weiss law with Curie constant of 0.423 cm³ K mol⁻¹ and with Weiss constant of −0.06 K. The magnetic moment of (2) exhibits a small increase with a decrease in the temperature (μ_eff = 1.80 B.M. at 300 K and μ_eff = 1.85 B.M. at 1.8 K) with Curie constant of 0.409 cm³ K mol⁻¹ and with Weiss constant of +1.1 K, which can indicate a very weak ferromagnetic interaction between the copper atoms within the chain. Applying the molecular field model resulted in obtaining zJ′ values −0.08 cm⁻¹ for complex (1), and −0.07 cm⁻¹ for complex (2), respectively, that could characterize intermolecular and interchain interactions transmitted through π–π stacking.     

Magnetostructural correlations and catecholase-like activities of μ-alkoxo-μ-carboxylato double bridged dinuclear and tetranuclear copper(II) complexes

Two μ-alkoxo-μ-carboxylato bridged dinuclear copper(II) complexes, [Cu₂(L¹)(μ-HCO₂)] (1) ((H₃L¹ = 1,3-bis(5-bromosalicylideneamino)-2-propanol)), [Cu₂(L²)(μ-HCO₂)] · dmf (2) (H₃L² = 1,3-bis(3,5-chlorosalicylideneamino-2-propanol)), and two μ-alkoxo-μ-dicarboxylato doubly bridged tetranuclear copper(II) complexes, [{Cu₂(L³)}₂(μ-O₂C–C(CH₃)₂–CO₂)] · 5H₂O · 3CH₃OH (3) ((H₃L³ = 1,3-bis(salicylid-deneamino)-2-propanol)) and [{Cu₂(L³)}₂(μ- O₂CCH₂–C₆H₄–CH₂CO₂)] · 2H₂O (4) have been prepared and characterized. The single crystal X-ray analysis shows that the structures of complexes 1 and 2 are dimeric with two adjacent copper(II) atoms bridged by μ-alkoxo-μ-carboxylato ligands with the Cu⋯Cu distances and Cu–O(alkoxo)–Cu angles are 3.511 Å and 132.85° for 1, 3.517 Å and 131.7° for 2, respectively. Complexes 3 and 4 consist of μ-alkoxo-μ-dicarboxylato doubly bridged tetranuclear Cu(II) complexes with mean Cu–Cu distances and Cu–O–Cu angles of 3.158 Å and 108.05° for 3 and 3.081 Å and 104.76° for 4, respectively. Magnetic measurements reveal that 1 and 2 are strong antiferromagnetically coupled with 2J = −156 and −152 cm⁻¹, respectively, while 3 and 4 exhibit ferromagnetic coupling with 2J = 86 and 155.2 cm⁻¹, respectively. The 2J values of 1–4 are linearly correlated to the Cu–O–Cu angles. Dependence of the pH at 25 °C on the reaction rate of oxidation of 3,4-di-tert-butylcatechol (3,5-dtbc) to the corresponding quinone catalyzed by 1–4 was studied. Complexes 1–4 exhibit high catecholase-like activity at pH 9.0 and 25 °C for oxidation of 3,5-di-tert-butylcatechol.     

DNA binding and photocleavage properties and apoptosis-inducing activities of a ruthenium porphyrin complex [(Py-3′)TPP-Ru(phen)2Cl]Cl and its heterometallic derivatives

The interactions of a ruthenium porphyrin complex [(Py-3′)TPP-Ru(phen)₂Cl]Cl (phen = 1,10-phenanthroline, (Py-3′)TPP = 5-(3′-pyridyl-10,15,20-triphenylporphyrin) (1) and its heterometallic derivatives, [Ni(Py-3′)TPP-Ru(phen)₂Cl][PF₆] (2) and [Cu(Py-3′)TPP-Ru(phen)₂Cl][PF₆] (3), with calf thymus DNA have been investigated by spectroscopic and viscosity measurements in this study. The results showed that these synthetic complexes can bind to double strand helix DNA in groove binding mode, and the intrinsic binding constants of complexes 1, 2 and 3, as calculated according to the decay of the Soret absorption, are (1.35 ± 0.5) ×10⁵ M^?1 (s = 4.2), (1.29 ± 0.5) × 10⁵ M^?1 (s = 5.6) and (1.22 ± 0.5) × 10⁵ M^?1 (s = 6.2) (s is the binding-site size), respectively, which are consistent with those obtained from ethidium bromide-quenching experiments. Further investigations on the photocleavage properties of these complexes on plasmid pBR 322 DNA showed that complexes 1, 2 and 3 could cleave single chain DNA and convert DNA molecules from supercoiled form to the nicked form. As determined by MTT assay, the complexes were also identified as potent antiproliferative agents against A375 human melanoma cells, MCF-7 human breast adrenocarcinoma cells, Colo201 human colon adenocarcinoma cells and HepG2 human liver cancer cells. Complex 1 inhibits the growth of A375 cells through induction of apoptotic cell death and G0/G1 cell cycle arrest. Further investigation on intracellular mechanisms indicated that Complex 1 induced depletion of mitochondrial membrane potential (ΔΨ_m) in A375 cells through regulating the expression of pro-survival and pro-apoptotic Bcl-2 family members. Our results suggest that ruthenium porphyrin complexes could be candidates for further evaluation as chemopreventive and chemotherapeutic agents for human cancers.     

Synthesis of water-soluble dinuclear metal complexes [metal = cobalt(II) and nickel(II)] and their behavior in solution

Two dinuclear metal complexes, [Co₂(bhmp)(MeCO₂)₂]ClO₄ · 2H₂O (1) and [Ni₂(bhmp)(MeCO₂)₂]ClO₄ · 2H₂O (2), were synthesized with a dinucleating ligand, 2,6-bis[bis(2-hydroxyethyl)aminomethyl]-4-methylphenol [H(bhmp)]. Both complexes were easily soluble in water as well as in DMF. Electronic spectra for both complexes were measured in both solvents and analyzed using the angular overlap model (AOM). From the electronic spectra and molar conductance, both complexes were determined to exist as [M₂(bhmp)(MeCO₂)₂]⁺ (M = Co^II or Ni^II) in DMF, dissociating perchlorate ions. On the other hand, in water, it was concluded that the acetate ions were partially dissociated and each complex existed as a mixture of some dissociated species, such as [M₂(bhmp)(MeCO₂)(H₂O)₂]²⁺ and [M₂(bhmp)(H₂O)₄]³⁺ (M = Co^II or Ni^II). Such dissociation was also confirmed by precipitation of the dissociated species when NaBPh₄ was added into an aqueous solution of the nickel complex.     

Ruthenium complexes of furan- and thiophene-thiolates: Structure of CpRu(dppe)SThi

Complexes of ruthenium containing 2-furan- and 2-thiophene-thiolates with phosphine ligands have been prepared and characterized. The bis(triphenylphosphine) complexes CpRu(PPh₃)₂SR (R = C₄H₃O: Fu (1a), C₄H₃S: Thi (1b)) were prepared by the reaction of thiolato anions (FuS^? or ThiS^?) with CpRu(PPh₃)₂Cl. The one-pot reaction of CpRu(PPh₃)₂Cl, thiolato anions and L ligands gave CpRu(L)SR (L = bis(diphenylphosphino)methane: dppm (2); bis(diphenylphosphino)ethane: dppe (3)). The newly prepared complexes have been characterized by spectroscopic techniques (FT-IR, ¹H NMR and ³¹P NMR) and by elemental analysis. The crystal structure of CpRu(dppe)SThi (3b) has been determined by X-ray diffraction.     

Homogeneous CO hydrogenation and transfer hydrogenation catalyzed by ruthenium(II) complexes containing optically active Ph2PCH(Ph)CH(Me)NH2 and 1,2-C5H8(PPh2)2 ligands

Combination of (1S,2S)-cyclopentanediylbis(diphenylphosphine) with [Ru(η⁴-C₈H₁₂){η³-(CH₂)₂CMe}₂] afforded the chelate complex [Ru{η³-(CH₂)₂CMe}₂{(1S,2S)-C₅H₈(PPh₂)₂}] (1), which gave (OC-6-13)-[RuCl₂{(1S,2S)-C₅H₈(PPh₂)₂}{(1S,2S)-Ph₂PCH(Ph)CH(Me)NH₂}] (2) upon reaction with methanolic HCl in acetone, followed by the addition of the β-aminophosphine in DMF. The (P ∩ N)₂-chelated complexes (OC-6-13)-[RuCl₂{(1S,2S)-Ph₂PCH(Ph)CH(Me)NH₂}₂] (3) and (OC-6-13)-[RuCl₂{(1R,2S)-Ph₂PCH(Ph)CH(Me)NH₂}₂] (4) resulted from RuCl₃ · 3H₂O and the P,N ligands under reducing conditions. The crystal structures of 3 and 4 were determined by single-crystal X-ray diffraction. Following activation by KOBu-t in isopropanol, compounds 2–4 catalyzed the enantioselective transfer hydrogenation of acetophenone with i-PrOH as the hydrogen source as well as the direct hydrogenation of the ketone by H₂ in low to moderate e.e. (up to 67%).     

Synthesis,structures and magnetic properties of pentanuclear and trinuclear heterometallic complexes with bended and linear cyano-bridges (tren = tris(2-aminoethyl)amine)

The reaction of [Cu(tren)(OH₂)](ClO₄)₂ with KCN gave a mononuclear complex [Cu(tren)(CN)](ClO₄) (1) (tren = tris(2-aminoethyl)amine). Using 1 as a building block, one pentanuclear compound, [{Cu(tren)(NC)}₄Ni](ClO₄)₆ (2) and two trinuclear complexes, [{Cu(tren)NC}₂Co(tren)](ClO₄)₅ · 2H₂O (3), [{Cu(tren)CN}₂NiL](ClO₄)₄ (4) (L = 3,10-bis(2-hydroxyethyl)-1,3,5,8,10,12-hexaazacyclotetradecane) were prepared and characterized by single crystal X-ray analysis. In 1, Cu(II) atom adopts a distorted trigonal bipyramidal (TBP) geometry. In 2, the Ni(II) atom occupies the center of the pentanuclear compound with a square-planar coordination geometry. In 3, the six-coordinated Co(III) atom presents a distorted octahedral geometry with four nitrogen atoms from tren and two carbon atoms of bridged cyano groups in cis-positions. In 4, the nickel atom is located in an inversion center and coordinated with two [(tren)CuCN]⁺ moieties through cyano-bridging ligands. Magnetic susceptibility measurements of 2–4 show that the magnetic interactions between the heterometallic ions are antiferromagnetical coupling through the cyano bridges with g = 2.25, J = −0.142 cm⁻¹ and J′ = −0.167 cm⁻¹ for 2, g = 2.06, J = −0.094 cm⁻¹ for 3, and g = 2.20, J = −33.133 cm⁻¹ for 4. The correlations between the structures and the J values are discussed.     

Structure–cytotoxic activity relationship of sesquilignan,morinol A

The cytotoxic activities of sesquilignans, (7S,8S,7′R,8′R)- and (7R,8R,7′S,8′S)-morinol A and (7S,8S,7′S,8′S)- and (7R,8R,7′R,8′R)-morinol B were compared, showing no significant difference between stereoisomers (IC₅₀ = 24–35 μM). As a next stage, the effect of substituents at 7, 7′, and 7″-aromatic ring on the activity was evaluated to find out the higher activity of (7S,8S,7′R,8′R)-7,7′,7″-phenyl derivative 18 (IC₅₀ = 6–7 μM). In the research on the structure–activity relationship of 7″-position of (7S,8S,7′R,8′R)-7,7′,7″-phenyl derivative 18, the most potent compounds were 7,7′,7″-phenyl derivative 18 (IC₅₀ = 6 μM) against HeLa cells. Against HL-60 cells, 7″-(4-nitrophenyl)-7,7′-phenyl derivative 33 and 7″-hexyl-7,7′-phenyl derivative 37 (IC₅₀ = 5 μM) showed highest activity. We discovered the compounds showed four to sevenfold potent activity than that of natural (7S,8S,7′R,8′R)-morinol A. It was also confirmed that the 7′-benzylic hydroxy group have an important role for exhibiting activity, on the other hand, the resonance system of cinnamyl structure is not crucial for the potent activity.     

Linear homobimetallic 4-thioacetyl-substituted NCN pincer palladium(II) and platinum(II) complexes with N-bidentate connecting units (NCN = [C6H2(CH2NMe2)2-2,6-R-4]−)

The synthesis and characterization of homobimetallic palladium and platinum complexes of type [(Me(O)CS-4-NCN–M ← N^∩N → M–NCN-4-SC(O)Me](OTf)₂ (Me(O)CS-4-NCN = [C₆H₂(CH₂NMe₂)₂-2,6-SC(O)Me-4]^?; N^∩N = 4,4′-bipyridine (bipy); M = Pd, 12; M = Pt, 13) is reported. The required bifunctional thio-acetyl NCN pincer starting compound NC(Br)N-4-SC(O)Me (2) has been synthesized by the consecutive reactions of NC(Br)N–I (I-1-C₆H₂(CH₂NMe₂)₂-3,5-Br-4) (1) with ^tBuLi, S₈ and Me(O)CCl, respectively. Chemoselective metallation at the C_aryl–Br bond was achieved by the reaction of 2 with the palladium(0) source [Pd₂(dba)₃] (3) (dba = dibenzylidene acetone). Treatment of thus formed [Pd(NCN-4-SC(O)Me)(Br)] (4) with [AgOTf] (8) (OTf = triflate, OSO₂CF₃) gave [Pd(NCN-4-SC(O)Me)(H₂O)][OTf] (9) which was further reacted with 0.5 equiv. of 4,4′-bipyridine (11a) to afford rigid-rod structured 12. When [Pt(tol)₂(SEt₂)]₂ (5) (tol = 4-tolyl) was used instead of 3, then 13 was produced via the in situ formation of [PtBr(NCN-4-SC(O)Me)] (7) and [Pt(NCN-4-SC(O)Me)(H₂O)][OTf] (10). Another possibility to synthesize 7 relied upon the subsequent reaction of 1 with 0.5 equiv. of 5 to give [PtBr(NCN-4-I)] (6) which further reacted with ^tBuLi, 1/8 S₈ and Me(O)CCl to afford 7. The cyclic voltammograms of 2, 7, and 13 are discussed.Complex 7 was structurally characterized by single crystal X-ray crystallography. Organometallic 7 crystallizes with three independent molecules in the asymmetric unit and displays a monomeric structure as commonly encountered in d⁸-metal pincer chemistry.     

(R)-3-Amino-1-((3aS,7aS)-octahydro-1H-indol-1-yl)-4-(2,4,5-trifluorophenyl)butan-1-one derivatives as potent inhibitors of dipeptidyl peptidase-4: Design,synthesis, biological evaluation,and molecular modeling

A series of (R)-3-amino-1-((3aS,7aS)-octahydro-1H-indol-1-yl)-4-(2,4,5-trifluorophenyl)butan-1-one derivatives was designed, synthesized, and evaluated as novel inhibitors of dipeptidyl peptidase-4 (DPP-4) for the treatment of type 2 diabetes. Most of the synthesized compounds demonstrated good inhibition activities against DPP-4. Among these, compounds 3e, 4c, 4l, and 4n exhibited prominent inhibition activities against DPP-4, with IC₅₀s of 0.07, 0.07, 0.14, and 0.17 μM, respectively. The possible binding modes of compounds 3e and 4n with dipeptidyl peptidase-4 were also explored by molecular docking simulation. These potent DPP-4 inhibitors were optimized for the absorption, distribution, metabolism, and excretion (ADME) properties, and compound 4n displayed an attractive pharmacokinetic profile (F = 96.3%, t_1/2 = 10.5 h).     

Electronic structure of [Ga2(tren)2(CAsq,cat)](BPh4)2(BF4): An EPR,ENDOR, and density functional study

The bimetallic [M₁M₂(tren)₂(CA^n?)]^m+ series, where M = Ga^III or Cr^III and CA is the chloranilate ligand which can take on diamagnetic (CA^cat,cat)^4? or paramagnetic (CA^sq,cat)^3? forms, comprises an electronically diverse series of compounds ranging from the closed-shell [Ga₂(tren)₂(CA^cat,cat)]²⁺ to the S = 5/2 ground state of [Cr₂(tren)₂(CA^sq,cat)]³⁺. This report deals with the interpretation of the EPR and ENDOR spectra of [Ga₂(tren)₂(CA^sq,cat)](BPh₄)₂(BF₄) (2) and the related derivative [Ga₂(tren)₂(DHBQ)](BPh₄)₂(BF₄) (2a) (where DHBQ is the fully deprotonated trianionic form of 2,5-dihydroxy-1,4-benzoquinone) in an effort to further characterize the electronic structure of this radical species. The X-band (～9.5 GHz) EPR spectrum of complex 2 acquired in a butyronitrile/propionitrile glass at 4 K reveals a rhombic g-tensor with g_xx = 2.0100, g_yy = 2.0097, and g_zz = 2.0060 with hyperfine interactions due to spin delocalization onto the two Ga nuclei (a_xx = 4.902 G, a_yy = 4.124 G, a_zz = 3.167 G); the origin of the hyperfine coupling was confirmed by analysis of the room temperature spectra of complexes 2 and 2a. The low-temperature spectrum of complex 2 also indicates the presence of a triplet electronic state characterized by a g-value of 2.009 and axial zero-field splitting of D = 150 G (0.012 cm^?1) as determined from measurements carried out at both X- and W-band (～95 GHz) frequencies. This triplet state is believed to arise due to a weak intermolecular Heisenberg exchange interaction between two aggregating complexes. ENDOR measurements on complex 2a at 20 K allowed for a determination of the magnitude of hyperfine coupling to the protons associated with the radical bridge as well as providing a rare example of an ENDOR signal arising from coupling to a gallium nucleus. Finally, these results were combined with literature data on the free semiquinone form of the bridging ligand in order to assess the extent to which density functional theory can predict unpaired spin density distribution in a complex molecule of this type. Although differences between theory and experiment were noted, DFT was able to provide a reasonably accurate picture of the electronic structure of this system as well as provide insight into the spin polarization mechanism(s) responsible for the observed hyperfine interactions.