Characterization of adducts produced in DNA by isomeric 1,2-diaminocyclohexaneplatinum(II) complexes

The cancer chemotherapeutic drug cis-diamminedichloroplatinum(II) (cis-DDP) is active as a result of its bifunctional reactions with DNA. Many other platinum complexes also have therapeutic activity. Of current interest are complexes containing 1,2-diaminocyclohexane (DACH). The DACH ligand exists in three isomeric forms with reported differences in therapeutic activity in the order R,R greater than S,S greater than R,S-DACH-Pt. The reaction of the sulphate form of each of these three isomers with DNA has been characterized as a possible explanation for the apparent differences in antitumor activity. These reactions have been characterized by platinating pure DNA followed by enzyme digestion, HPLC separation and analysis by atomic absorption and nuclear magnetic resonance. The spectrum of adducts produced was similar for each isomer and similar to that reported for cis-DDP with adduction at d(GpG), d(ApG) and (dG)2. The R,S-isomer additionally demonstrated isomeric adducts at d(GpG) and d(ApG). The kinetics of formation of the various adducts was the same for each isomer; total platination of DNA was complete in 15 min as were bifunctional adducts at d(GpG) and (dG)2. However, rearrangement to bifunctional adducts took several hours in the case of adducts at d(ApG) sequences. These results did not provide a reason for the different activities of the isomers. It is suggested that the interaction of these adducts with metabolic processes such as DNA repair might explain these differences.     

Structures, spectroscopy and modeling of a rare set of isomeric copper(II) complexes

The structures and spectroscopic properties of various conformations of two diasteromeric pairs of enantiomers of pentacoordinate Cu^II bispidine complexes with chiral tetradentate ligands are reported. With one of the ligands an interesting type of distortional isomerism was observed experimentally, and this was studied in detail on the basis of the experimental structural and spectroscopic data (UV-Vis-NIR, EPR) and a DFT-, MM- and ligand-field-theory-based analysis.     

Cationic ligands for Ag(I): Organometallic polymers versus unimolecular complexes

We have prepared and characterized two cationic ligands and their Ag(I) coordination compounds. For the bidentate ligand 2, 2,2-bis-pyridin-2-ylmethyl-2,3-dihydro-1H-isoindolium bromide, we obtained the organometallic polymer [AgL]_x[CF₃SO₃]_2x (4), and the unimolecular complex [AgL₂][PF₆]₃ (5). Compound 4 exists as an organometallic linear polymer with triflate anions either bonded to Ag(I) or non-bonded and sandwiched between the polymer chains. Complex 5 is the only unimolecular example in this series due to the non-interaction of anions with Ag(I) or with the cationic portion of the ligand. In the case of the tridentate cationic ligand 3-(3-pyridin-2-yl-2-pyridin-2-ylmethy-propyl)-benzyl-triethylammonium bromide (3), two dimeric Ag(I) complexes are formed, [Ag₂L₂][CF₃SO₃]₄ (6), and [Ag₂(CH₃CN₂)₂L₂][PF₆]₄ (7). Both of these dimers have essentially similar structures, with a closed-shell Ag(I)?Ag(I) interaction of approximately 3.00 Å in both cases; the pyridyl moieties of the ligands are forced into an electronically unfavourable face-to-face arrangement. The coordination spheres of the Ag(I) cations are completed by in the case of 6, and by CH₃CN solvent in the case of 7. In the extended packing diagrams, the arrangements of 6 and 7 are driven by intermolecular π-stacking and cation-anion interactions.     

Synthesis and crystal structure of a salicylatooxovanadium(V) complex of an aminebis(phenolate) ligand: Kinetic studies on its formation from corresponding alkoxo complexes

Synthesis and single crystal X-ray structures of H₂L¹ and VO(L¹)(HL) [H₂L¹ = N,N-bis(2-hydroxy-3,5-ditertiarybutyl)-N′,N′-dimethylethylendiamine) or simply aminebis(phenol) and H₂L = salicylic acid) are reported here. The complex [VO(L¹)(HL)] is in distorted octahedral geometry under O₄N₂ donor environment where the basal core is defined by O(1), O(3), O(2) and N(5) atoms and two axial coordinates are occupied by O(4), an alkoxo-group and N(1), an imino-nitrogen atom. The electron spray mass spectrometric study on [VO(L¹)(HL)] in MeCN clearly points out the existence of single species in solution. Again, the ⁵¹V NMR of the bulk polycrystalline sample reveals that the complex [VO(L¹)(HL)] mainly exists in three out of four possible isomers. The formation of [VO(L¹)(HL)] from both [VO(L¹)(OMe)] and [VO(L¹)(OEt)] was followed kinetically by reacting with salicylic acid in MeCN. The presence of isosbestic point indicates a clean conversion of the reactants to product.     

Resonance Raman spectroscopie investigations on phenolate bridged binuclear Cu(II) complexes: A basis for the identification of the endogenous bridging

Phenolate bridged binuclear Cu(II) complexes were used to monitor the contribution of the endogenous bridging ligand to the resonance Raman spectrum of the oxygen transport protein such as hemocyanin. From the excitation profile of the intensity enhanced phenolate v_c-o the phenolate-to-Cu(II) charge-transfer transition of the four studied complexes has been located between 380 nm and 430 run, similar to the low-temperature absorption band in the hemocyanin spectra. By approaching the exciting laser frequency to this electronic transition, the whole spectral range 1250–1650 cm⁻¹ is strongly intensity enhanced and considered as the typical feature of this kind of phenolate bridged Cu(II) complexes. Comparison to mononuclear analogues pointed out no significant differences of the resonance enhanced Raman lines. The results are discussed in relation to the resonance Raman spectra of hemocyanin.     

WASP-interacting protein (WIP): working in polymerisation and much more

The migration of cells and the movement of some intracellular pathogens, such as Shigella and Vaccinia, are dependent on the actin-based cytoskeleton. Many proteins are involved in regulating the dynamics of the actin-based microfilaments within cells and, among them, WASP and N-WASP have a significant role in the regulation of actin polymerisation. The activity and stability of WASP is regulated by its cellular partner WASP-interacting protein (WIP) during the formation of actin-rich structures, including the immune synapse, filopodia, lamellipodia, stress fibres and podosomes. Here, we review the role of WIP in regulating WASP function by stabilising WASP and shuttling WASP to areas of actin assembly in addition to reviewing the WASP-independent functions of WIP.     

The synthesis and characterisation of phenolate complexes of Cu(II) and Ni(II) that are capable of supporting a phenoxyl radical ligand

New Cu^II and Ni^II complexes of potentially tridentate N₂O Schiff base ligands 1 and 2 have been synthesised and characterised. [Cu(2)(OH₂)]⁺ possesses a square planar geometry in the solid state whereas [Ni(1)₂] possesses a distorted octahedral geometry in which the amine donors of 1 coordinate weakly to the Ni^II centre. EPR spectroscopy demonstrates that the N₂O₂ coordination sphere of [Cu(2)(OH₂)]⁺ is retained in CH₂Cl₂ solution. [Cu(2)(OH₂)]⁺ exhibits a reversible one electron oxidation at E_1/2 = 0.54 V versus [Fc]⁺/[Fc], the product of which has been characterised by UV-Vis absorption and EPR spectroscopies. The spectroscopic signature of the oxidised product is consistent with the formation of a stable phenoxyl radical ligand bound to a Cu^II centre. [Ni(1)₂] possesses a reversible metal-based oxidation process at E_1/2 = 0.03 V versus [Fc]⁺/[Fc] and a further oxidation, attributed to the generation of a phenoxyl radical centre, at  = 0.44 V versus [Fc]⁺/[Fc]. UV-Vis absorption and EPR spectroscopic studies indicate that the lower potential process is a formal Ni^III/II couple. In contrast, the pro-ligands 1H and 2H exhibit chemically irreversible oxidation processes at  = 0.42 and 0.40 V versus Fc⁺/Fc, respectively, and do not support the formation of stable phenoxyl radical species.     

Synthesis, reactivities and catalytic carbonylation of rhodium(I) carbonyl complexes containing isomeric acetylpyridine ligands

[Rh(CO)₂Cl]₂ reacts with two mole equivalent of 2-acetylpyridine (a), 3-acetylpyridine (b) and 4-acetylpyridine (c) to afford chelate [Rh(CO)Cl(η²-N∩O)] (1a) and non-chelate [Rh(CO)₂Cl(η¹-N∼O)] (1b, 1c) complexes, where, N∩O = a, N∼O = b, c. Oxidative addition (OA) of 1a-1c with CH₃I and C₂H₅I yields penta coordinate rhodium(III) complexes, [Rh(COR)ClI(η²-N∩O)] {R = -CH₃ (2a); -C₂H₅ (3a)} and [Rh(COR)(CO)ClI(η¹-N∼O)] {R = -CH₃ (2b, 2c); -C₂H₅ (3b, 3c)}. Kinetic study for the reaction of 1a-1c with CH₃I indicates a pseudo-first order reaction. The catalytic activity of 1a-1c for the carbonylation of methanol to acetic acid and its ester was evaluated at different initial CO pressures 5, 10 and 20 bar at ∼25 °C and higher turn over numbers (TON = 1581-1654) were obtained compared to commercial Monsanto’s species [Rh(CO)₂I₂]⁻ (TON = 1000) under the reaction conditions: temperature = 130 ± 1 °C, pressure = 15-32 bar, rpm = 450, time = 1 h and catalyst: substrate = 1: 1900.     

Chiral bimetallic complexes from chiral salen metal complexes and mercury (II) halides and acetates: the anionic groups interact with Cu(II) in apical position

A series of chiral bimetallic complexes have been prepared containing both Cu(II) and Hg(II) metal centers. The complexes possess chiral salen ligands which host Cu(II) in the center of the cis-N₂O₂ chromophore and Hg(II) via two oxygen atoms of the chromophore. Halogen and acetate groups from mercury salts interact with the Cu(II) center. The X-ray crystallographic data of 11 reveals a short distance of Cl?Cu (3.22-3.26 Å). EPR study also discloses a strong interaction, in particular, of acetate group with Cu.     

Copper(II) complexes with phenoxyalkanoic acids and nitrogen donor heterocyclic ligands: structure and bioactivity

The copper complexes with the phenoxyalkanoic acids MCPA, 2,4-D, 2,4,5-T and 2,4-DP in the presence of a nitrogen donor heterocyclic ligand, phen or bipyam, were prepared and characterized. Interaction of Cu(II) with phenoxyalkanoic acids and bipyam leads to dinuclear or uninuclear neutral complexes while in the presence of phen uninuclear neutral or cationic forms have been isolated. The crystal structure of bis(1,10-phenanthroline)(2-methyl-4-chloro-phenoxyacetato)copper(ll) chloride-methanol(1/1)-water(1/0.6), 1 has been determined and refined by least-squares methods using three-dimensional MoK, data. 1 crystallizes in space group P1, in a cell of dimensions a = 14.577(6)A, b = 1 1.665(5) A, c = 12.249(6) A, alpha = 98.38( 1)degrees, beta = 112.18( 1) degrees, gamma = 104.56(1 ) degrees, V= 1,798( 1) A3 and Z= 2. The cyclic voltammograms of uninuclear cationic complexes in dmf exhibit an extra cathodic wave due to the chloride ion. The available evidence supports an increasing antimicrobial effeciency for the cationic complexes.     

Asymmetric hydroformylation with highly crosslinked polystyrene-supported (R,S)-BINAPHOS-Rh(I) complexes: the effect of immobilization position

A new class of polymer-supported (R,S)-BINAPHOS 1e in which the parent BINAPHOS has two alkoxy-substituents at the 3-positions of the phenyls, has been synthesised. Using its Rh(I) complex, asymmetric hydroformylation of olefins proceeded with higher enantioselectivity in some cases compared to the conventional polymer-supported 1c.     

Synthesis and biological studies of neutral technetium (V) complexes containing NNOS donor sets

Complexation of ligands containing an N₃S donor set has been affected with [^99mTc]. These are part of a ligand series of analogous structures which exhibit similar chemistry and potentially interesting biology. The complexes which have been characterized with [^33mTc]as [TcOL] are neutral and lipophilic and their biological behaviour has been assessed in rats. After HPLC purification of the no-carrier added preparation, brain uptake of the tracers was > 1% at 15 min p.i. Muscle activity was significant with slow blood clearance.     

Site-specific electronic couplings in dyads with MLCT excited states. Intramolecular energy transfer in isomeric Ru(II)-Ru(II) cyclometalated complexes.

The rod-like binuclear complexes [(ttpy)Ru(tpy-ph(2)-phbpy)Ru(ttpy)](4+) and [(ttpy)Ru(tpy-ph(2)-tpy)Ru(phtbpy)](4+) (for abbreviations, see text) have been synthesized and characterized. In both complexes, the polypyridine Ru(II) centers have (N--N--N)Ru(N--N--N) and (N--N--N)Ru(C--N--N) coordination environment. The two isomeric species differ in whether the cyclometalating carbon resides on the bridging or on the terminal ligand. The two complexes have virtually identical energy levels, but MLCT excited states of different (bridging or terminal) ligand localization. They are thus ideally suited to investigate possible effects of excited-state localization on intramolecular energy transfer kinetics. In fact, ultrafast spectroscopic measurements yield different energy transfer time constants for the two isomers, with the bridge-cyclometalated complex (2.7 ps) being faster than the terminal-cyclometalated one (8.0 ps). This difference can be explained in terms of different electronic factors for Dexter energy transfer. The study highlights the peculiar intricacies of intramolecular energy transfer in inorganic dyads involving MLCT excited states.     

Ring-opening polymerisation of beta-butyrolactone catalysed by distannoxane complexes: study of the mechanism.

The mechanism of the ring-opening polymerisation of beta-butyrolactones was studied. The ring-opening polymerisation of BL catatlysed by distannoxane complexes is of a living nature. The polymerisation of racemic BL gave a predominantly syndiotactic P(3HB). The temperature effect on syndiospecificity was used to determine the activation energy (deltaE = Esyndiotactic - Eisotactic) for syndiotactic versus isotactic diad placement. The deltaE value was obtained as -1.49 kcal/mol. The steric control leading to the observed syndiospecificity is due predominantly to diastereomeric interactions between the Sn-coordinated P(3HB) chain end. having a specific chain end stereochemistry, and the incoming BL enantiomeric monomers. The catalytic cycle derived from the mechanism of the polymerisation was proposed.     

Copper (II) complexes with N,S donor pyrazole-based ligands as anticancer agents

BioMetals - A group of bidentate nitrogen and sulfur donor pyrazole derivative ligands abbreviated as Na[RNCS(Pz)], Na[RNCS(PzMe2)], Na[RNCS(PzMe3)], Na[RNCS(PzPhMe)], Na[RNCS(PzPh2)], where...     

Guanine versus deoxyribose damage in DNA oxidation mediated by vanadium(IV) and vanadium(V) complexes

Vanadyl sulfate reacts with the peroxy acid oxidant KHSO5 to produce guanine-selective oxidation of a 167-bp restriction fragment of DNA. The oxidized lesions result in strand scission after hot piperidine treatment. Although several reactive intermediates are possible, quenching studies with ethanol and tert-butyl alcohol suggest that a monoperoxysulfate radical or a caged sulfate radical are the likely species responsible for oxidation of guanine. Several oxidants and various vanadium complexes (including insulin mimetic compounds) were studied with DNA for comparison. None of the other vanadium complexes showed modification of the double-stranded 167-bp fragment of DNA in the presence of KHSO5. The reactivity of VOSO4 may be due to its irreversible oxidation potential of 0.77 V (vs. Ag+/AgCl, pH 7.0, 10 mM phosphate), making it an appropriate catalyst for decomposition of monoperoxysulfate.     

Binuclear manganese(III) complexes of an unsymmetric pyrazolate-based compartmental ligand with hard donor set

The synthesis, crystal structure and magnetic properties of manganese(III) binuclear complexes [Mn^III₂(L-3Н)₂(CH₃ОH)₄]·2CH₃ОH (1) and [Mn^III₂(L-3Н)₂(Py)₄]·2Py (2) (L = 3-[(1E)-N-hydroxyethanimidoyl]-4-methyl-1H-pyrazole-5-carboxylic acid) are reported. The ligand contains two distinct donor compartments formed by the pyrazolate-N and the oxime or the carboxylic groups. The complexes were characterized by X-ray single crystal diffraction, revealing that both 1 and 2 consist of dinuclear units in which the two metal ions are linked by double pyrazolate bridges with a planar {Mn₂N₄} core. Cryomagnetic measurements show antiferromagnetic interaction with g = 1.99, J = −3.6 cm⁻¹, Θ = −2.02 K for 1 and g = 2.00, J = −3.7 cm⁻¹, Θ = 1.43 K for 2.     

Crystal Structure of Circular Permuted RoCBM21 (CP90): Dimerisation and Proximity of Binding Sites

Glucoamylases, containing starch-binding domains (SBD), have a wide range of scientific and industrial applications. Random mutagenesis and DNA shuffling of the gene encoding a starch-binding domain have resulted in only minor improvements in the affinities of the corresponding protein to their ligands, whereas circular permutation of the RoCBM21 substantially improved its binding affinity and selectivity towards longer-chain carbohydrates. For the study reported herein, we used a standard soluble ligand (amylose EX-I) to characterize the functional and structural aspects of circularly permuted RoCBM21 (CP90). Site-directed mutagenesis and the analysis of crystal structure reveal the dimerisation and an altered binding path, which may be responsible for improved affinity and altered selectivity of this newly created starch-binding domain. The functional and structural characterization of CP90 suggests that it has significant potential in industrial applications.     

The role of cyclopentadienyl versus indenyl in Mo(II) spirodiene complexes reactivity: A DFT mechanistic study

Spiro[2,4]hepta-4,6-diene and spiro[4,4]nona-1,3-diene react with [Mo(CO)₂Cp’(NCCH₃)₂][BF₄] (Cp’ = Cp, Ind; Ind = η⁵-C₉H₇) to afford the corresponding diene complex [Mo(diene)(CO)₂Cp′]⁺. When Cp’ = Ind, the reaction proceeded forward leading to ring opening in the case of the small spiro ring. Although this and another product resulting from migration of the side arm to the carbonyl were detected when Cp’ = Cp, they did not form from the diene complex. A DFT/PBE1PBE study was carried out and showed a kinetically controlled reaction pathway leading from the [Mo(diene)(CO)₂Ind]⁺ to the reaction product, with an activation barrier of 21.3 kcal mol⁻¹. The thermodynamic preferred species was the non-observed complex (insertion), and its formation required higher barriers. In the presence of Cp, all the barriers increased significantly, explaining the inertness of the initial diene complex. The interpretation of this behaviour is associated with the ease of the η⁵ → η³ haptotropic rearrangement of the indenyl, which helps to lower some relevant barriers. This route is not available for the Cp analogue.