EPR Study of some Copper(II) Coordination Compounds with substituted Biguanides. III

Copper(II) coordination compounds with p-chlorphenylbiguanide of the type: [Cu(Cl-PhBig)₂]X₂ and [Cu(Cl–PhBig)X₂] with X =Cl^?, Br^? NO₃, OH^?, NCS^?, NCO^?, N₃, have been studied by EPR spectroscopy using polycrytalline powders and solutions in DMF. The parameters of the EPR spectra have been used to estimate molecular orbital coefficient, in these compounds and to discuss details of the chemical bonding.     

Substitution of [Pt(terpy)H2O]2+ and [Pt(bpma)H2O]2+ with thiols in acidic aqueous solution. terpy = 2,2′:6′2″-terpyridine; bpma = bis(2-pyridylmethyl)amine

The substitution behaviour of [Pt(terpy)H₂O]²⁺ and [Pt(bpma)H₂O]²⁺, where terpy is 2,2:62-terpyridine and bpma is bis(2-pyridylmethyl)amine, was studied as a function of entering thiol concentration and temperature. The reactions between the Pt-complexes and DL-penicillamine, L-cysteine and glutathione were carried out in a 0.10 mol dm^–3 aqueous HClO₄ medium using stopped-flow and conventional u.v.–vis spectrophotometry. The observed pseudo-first-order rate constants for the substitutions are given by k _obs = k ₂[thiol] + k _–2. The k _–2 term represents the reverse solvolysis. This was found to be zero for Pt^II(terpy) which was the most reactive complex. The second-order rate constants, k ₂, for the three thiols varied between 0.107 ± 0.001 and 0.517 ± 0.025 M^–1 s^–1 for Pt^II(bpma) and 10.7 ± 0.7–711.9 ± 18.3 M^–1 S^–1 for Pt^II(terpy), whereas glutathione was found to be the strongest nucleophile. An analysis of the activation parameters, H and S , clearly shows that the substitution process is associative in nature.     

A mechanistic investigation of the carbon-carbon bond cleavage of aryl and alkyl cyanides using a cationic RhIII silyl complex

Cationic Rh(III) complex [Cp(PMe(3))Rh(SiPh(3))(CH(2)Cl(2))]BAr(4)' (1) activates the carbon-carbon bond of aryl and alkyl cyanides (R-CN, where R = Ph, (4-(CF(3))C(6)H(4)), (4-(OMe)C(6)H(4)), Me, (i)Pr, (t)Bu) to produce complexes of the general formula [Cp*(PMe(3))Rh(R)(CNSiPh(3))]BAr(4)'. With the exception of the (t)BuCN case, every reaction proceeds at room temperature (t(1/2) < 1 h for aryl cyanides, t(1/2) < 14 h for alkyl cyanides). A general mechanism is presented on the basis of (1) an X-ray crystal structure determination of an intermediate isolated from the reaction involving 4-methoxybenzonitrile and (2) kinetic studies performed on the C-C bond cleavage of para-substituted aryl cyanides. Initial formation of an eta(1)-nitrile species is observed, followed by conversion to an eta(2)-iminoacyl intermediate, which was observed to undergo migration of R (aryl or alkyl) to rhodium to form the product [Cp*(PMe(3))Rh(R)(CNSiPh(3))]BAr(4)'.     

Janus-type isopropyl groups revealed by 1H-NMR spectra of alkylpyridines with lanthanide shift reagents (LSR)

Two Isomeric pyridines were designed and prepared : 2-isopropyl-4,5,6-trimethyl-(3) and 2-isopropyl-3,4,6-trimethyl-pyridine (7); the latter, with a buttressed isopropyl, leads to much lower induced shifts by Eu(dpm)₃ and Pr(dpm)₃ than the former, owing to the conformation in which the Janus-type iPr group how to the LSR a t-butyl-like face.     

Rh(II) and Rh(I) two-legged piano-stool complexes: structure,reactivity, and electronic properties

The ligand 1,4-bis[4-(diphenylphosphino)butyl]-2,3,5,6-tetramethylbenzene, 3, was used to synthesize a mononuclear Rh(II) complex [(eta(1):eta(6):eta(1)-1,4-bis[4-(diphenylphosphino)butyl]-2,3,5,6-tetramethylbenzene)Rh][PF(6)](2), 6+, in a two-legged piano-stool geometry. The structural and electronic properties of this novel complex including a single-crystal EPR analysis are reported. The complex can be cleanly interconverted with its Rh(I) form, allowing for a comparison of the structural properties and reactivity of both oxidation states. The Rh(I) form 6 reacts with CO, tert-butyl isocyanide, and acetonitrile to form a series of 15-membered mononuclear cyclophanes [(eta(1):eta(1)-1,4-bis[4-(diphenylphosphino)butyl]-2,3,5,6-tetramethylbenzene)Rh(CO)(3)][PF(6)] (8), [(eta(1):eta(1)-1,4-bis[4-(diphenylphosphino)butyl]-2,3,5,6-tetramethylbenzene)Rh(CNC(CH(3))(3))(2)][PF(6)] (10), and [(eta(1):eta(1)-1,4-bis[4-(diphenylphosphino)butyl]-2,3,5,6-tetramethylbenzene)Rh(CO)(CH(3)CN)][PF(6)] (11). The Rh(II) complex 6+ reacts with the same small molecules, but over shorter periods of time, to form the same Rh(I) products. In addition, a model two-legged piano-stool complex [(eta(1):eta(6):eta(1)-1,4-bis[3-(diphenylphosphino)propoxy]-2,3,5,6-tetramethylbenzene)Rh][B(C(6)F(5))(4)], 5, has been synthesized and characterized for comparison purposes. The solid-state structures of complexes 5, 6, 6+, and 11 are reported. Structure data for 5: triclinic; P(-)1; a = 10.1587(7) A; b = 11.5228(8) A; c = 17.2381(12) A; alpha = 96.4379(13) degrees; beta = 91.1870(12) degrees; gamma = 106.1470(13) degrees; Z = 2. 6: triclinic; P(-)1; a = 11.1934(5) A; b = 12.4807(6) A; c = 16.1771(7) A; alpha = 81.935(7) degrees; beta = 89.943(1) degrees; gamma = 78.292(1) degrees; Z = 2. 6+: monoclinic; P2(1)/n; a = 11.9371(18) A; b = 32.401(5) A; c = 12.782(2) A; beta = 102.890(3) degrees; Z = 4. 11: triclinic; P(-)1; a = 13.5476(7) A; b = 13.8306(7) A; c = 14.9948(8) A; alpha = 74.551(1) degrees; beta = 73.895(1) degrees; gamma = 66.046(1) degrees; Z = 2.     

Phosphorus-based SAHA analogues as histone deacetylase inhibitors

[structure: see text] Three analogues of suberoyl anilide hydroxamic acid (SAHA) with phosphorus metal-chelating functionalities were synthesized as inhibitors of histone deacetylases (HDACs). The compounds showed weak activity for HeLa nuclear extracts (IC(50) = 0.57-6.1 mM), HDAC8 (IC(50) = 0.28-0.41 mM), and histone-deacetylase-like protein (HDLP, IC(50) = 0.33-1.9 mM), suggesting that the transition state of HDAC is not analogous to zinc proteases. Antiproliferative activity against A2780 cancer cells (IC(50) = 0.11-0.12 mM), comparable to SAHA (0.15 mM), was observed.     

Design and Enantioselective Synthesis of a Peptidomimetic of the Turn in the Helix-Turn-Helix DNA-Binding Protein Motif

A peptidomimetic of the turn in the helix-turn-helix (HTH) motif of DNA-binding proteins was designed and synthesized. Conformational constraint was achieved by an unusual linking of two amino acids with a side chain carbon-carbon bond. A phenyl ring provides the potential for new hydrophobic contacts with the hydrophobic core of the HTH motif. In the mimic, the peptide backbone and the central residue were retained in native form within a 12-membered cyclic tripeptide. The target compound 1b was synthesized by two sequential Horner-Wittig couplings followed by enantioselective hydrogenation with Rh(MeDuPHOS) in eight steps and 35% overall yield. The stereochemical outcome of the key hydrogenation was determined by aromatic ring oxidation with RuO(2)/NaIO(4) to give 2 equiv of Boc-Asp-OMe.     

Determination of glucosamine in raw materials and dietary supplements containing glucosamine sulfate and/or glucosamine hydrochloride by high-performance liquid chromatography with FMOC-Su derivatization: collaborative study

A collaborative study was conducted for determination of glucosamine in raw materials and dietary supplements containing glucosamine sulfate and/or glucosamine hydrochloride by high-performance liquid chromatography (HPLC) with N-(9-fluorenyl-methoxycarbonyloxy) succinimide (FMOC-Su) derivatization. Thirteen blind materials, one pair of which were duplicates, were tested by 12 collaborating laboratories. The test samples consisted of various commercial products, including tablets, capsules, drink mix, and liquids as well as raw materials, blanks, and those for spike recovery analyses. The tests with blank products and products spiked with glucosamine showed good specificity of the method. The average recoveries at spike levels of 100 and 150% of the declared amount were 99.0% with a relative standard deviation (RSD) of 2.1%, and 101% with an RSD of 2.3%, respectively. The test results between laboratories on each commercial product were reproducible with RSD values of no more than 4.0%, and the results were repeatable in the same laboratory with an average RSD of 0.7%. HorRat values ranged from 0.5 to 1.7 on both tests of spike recovery and reproducibility between laboratories on commercial products. The average determination coefficient of the calibration curves from the laboratories was 0.9995 with an RSD of 0.03%. All of the 12 collaborating laboratories succeeded in the study and none of their reported test results were outliers, partly indicating the robustness of the method. It is recommended that the method be accepted by AOAC INTERNATIONAL as Official First Action.     

Spectroscopic investigation of β-cyclodextrin -metoprolol tartrate inclusion complexes

Aqueous-solution complexes of β-cyclodextrin (β-CD) with metoprolol tartrate (MET) have been analysed with ¹H NMR and UV–vis spectroscopy. With ¹H NMR a [1:1] stoichiometry could be established for the β-CD-MET complex while its stability constant was determined with UV–vis spectroscopy. Powder diffraction data of a polycrystalline sample of the β-CD-MET complex show that a novel product has been formed, likely to be a β-CD-MET [1:1] inclusion complex. Also Hyperchem MM+ molecular-dynamics results suggest an inclusion complex and from ¹H NMR data it is inferred that probably the MET is docked in the CD with the formers methoxyethyl-benzene moiety in front. Mihaela Toma is Socrates/Erasmus student at UNED Madrid     

Stereochemistry of cyclobutanone resulted from cycloadditions of t-butylcyanoketene to bicyclo[2.2.1]heptene derivatives, as evidence for a π2s+π2a reaction mode

The stereochemistry of the cyclobutanones 1-7, resulted from the reaction of t-butylcyanoketene with bicyclo[2.2.1]heptene, bicyclo[2.2.1]heptadiene, 1,4 - dihydro - 1,4 - methanonaphthalene, 1,4 - dihydro - 9 - (1 - methylethylidene) - 1,4 - methanonaphthalene, 1,4 - dihydro - 1,4 - epoxynaphthalene, l,4,4a,8b - tetrahydro - 1,4 - methanobiphenylene (l,4,4a,8b) and 1,4,4a,8b - tetrahydro - 1,4 - methanobiphenylene(1,4,4aβ,8bβ) was established as having the cyclobutanone ring exo and the t-Bu group in the configuration. These findings represent a stereochemical argument in favour of a _π2_s + _π2_a reaction mode of t-butylcyanoketene to the above mentioned bicyclo[2.2.1]heptene derivatives. Observations regarding preservation of the original configurations of alkenes as well as the geometrical distorsion of the cyclobutanones are shortly discussed.