Photophysical studies of hetero-bischelated complexes of rhodium(III) containing 2,2′-dipyridylamine

Four mixed-ligand complexes, cis-Rh[(bipy)(HDPA)Cl₂]Cl (1), cis-[Rh(phen)(HDPA)Cl₂]Cl (2), cis-[Rh(bipy)(DPA)Cl₂] (3), and cis-[Rh(phen)(DPA)Cl₂] (4) (where bipy = 2,2′-bipyridine, phen = 1,10-phenantroline, HDPA = 2,2′-dipyridylamine, and DPA = the deprotonated form of 2,2′-dipyridylamine) have been synthesized and characterized. In slightly acidic solution and at low temperature (77 K), both complexes 1 and 2 show a broad, symmetric and structureless red emission with microsecond lifetime identified as dd* phosphorescence. In slightly basic solution, the deprotonated complexes (3 and 4) exhibit a broad and asymmetric blue emission, showing no vibrational structure with a lifetime in the order of microseconds. Emission of complex 3 reveals a blue shift of 0.81 μm⁻¹ compared to the emission of complex 1 and that of complex 4 shows a blue shift of 0.77 μm⁻¹ with respect to complex 2. Electrochemical data have also been obtained for the four complexes in CH₃CN. There are two reduction peaks observed for both complexes 1 and 2. Each peak is followed by a one-electron reduction at the metal, with an elimination of chloride during each reduction step, which is in consistent with the dd* phosphorescence assignment for the two complexes. For complexes 3 and 4, only a one-electron reduction process occurs at the metal with an elimination of chloride. Based on the luminescence and electrochemical data, the emission of complexes 3 and 4 are assigned as πd* phosphorescence. Results from density functional theory (DFT) calculations provide theoretical evidence in support of this πd* assignments.     

Efficient synthesis of the cyclometalated complex fac-[Rh(ppy)3] (ppy = 2-phenylpyridinato)

A new convenient high-yield synthesis of the tris-cyclometalated complexes fac-[Rh(ppy)₃] (4; ppy = 2-phenylpyridinato) was developed. Complex 4 was prepared in a kind of one-pot synthesis starting from in situ prepared [Rh(acac)(coe)₂] (2) which was heated in refluxing 2-phenylpyridine for a short time. After purification by filtration over alumina, compound 4 was obtained in yields of 65%. Also [Rh(acac)(ppy)₂] (3) was prepared in a similar manner by oxidative addition of Hppy in refluxing toluene in high yields. In contrast to previous findings with the analogous iridium compounds, there was not any hint at the formation of the isomer mer-[Rh(ppy)₃] using similar reaction conditions as applied for iridium. Furthermore the compound [{Rh(μ-Cl)(ppy)₂}₂] (5) was prepared from [{Rh(μ-Cl)(coe)₂}₂] (1) and Hppy in refluxing toluene in nearly quantitative yield.     

Novel rhodium complexes containing a bulky iminophosphine ligand and their use as catalysts for the hydroboration of vinylarenes

Addition of o-Ph₂PC₆H₄CHN-2,6-ⁱPr₂C₆H₃ (1) to [RhCl(coe)₂]₂ (coe = cis-cycloctene) gave several new iminophosphino rhodium(I) complexes including [Rh(κ²-o-Ph₂PC₆H₄CHN-2,6-ⁱPr₂C₆H₃)(μ-Cl)]₂ (2). Addition of 1 to Rh(acac)(coe)₂ (acac = acetylacetonato) gave [Rh(acac)(κ²-o-Ph₂PC₆H₄CHN-2,6-ⁱPr₂C₆H₃)] (3) in yields of up to 75%. Complex 3 has been examined for its ability to catalyze the hydroboration of a series of vinyl arenes. Reactions using catecholborane and pinacolborane seem to proceed largely through a dehydrogenative borylation mechanism to give a number of boronated products.     

The synthesis and structural properties of [M(dippe)(η2-C4H4S)] complexes of Pd and Pt and comparison with their Ni analog

X-ray structural and NMR spectroscopic data for the ring-opened thiophene complexes [Pd(dippe)(T)] (2), and [Pt(dippe)(T)] (3) are now presented. The complex [Ni(dippe)(T)] (1), where T = (η²-C,S-C₄H₄S), was reported by our group, previously.The structural and bonding properties of complexes 2 and 3 were compared with those of complex 1. DFT calculations were carried out to rationalize their relative stabilities and structural properties. Compound 1 loses thiophene at ambient temperature in solution, while compound 2 decomposes rapidly in both acetone-d₆ and THF-d₈ with k_obs = 7.15(9) × 10⁻⁵ and 7.7(3) × 10⁻⁵ s⁻¹, respectively, to give products that varied by solvent. Complex 3 does not lose thiophene at temperatures below 100 °C. The ΔG⁰ values determined from DFT calculations are consistent with the observed stabilities of the complexes. The single crystal X-ray structures of all three complexes contain a disordered thienyl fragment in the asymmetric unit due to the interchange of the position of sulfur in the metal-inserted thiophenic ring. The thiophenic moiety is relatively flat in 1, 2 and 3, which is attributed to the open ligand environment at the M(dippe) fragment. All three complexes possess square-planar geometry around the metal center and have bond-length alternation among the thiophenic carbons, which indicates double bond localization. The calculated bond lengths are in good agreement with experimental data. Molecular orbital (MO) and natural bonding orbital (NBO) analyses were carried out to rationalize the results.     

Mononuclear arene ruthenium complexes containing 5,6-diphenyl-3-(pyridine-2-yl)-1,2,4-triazine as chelating ligand: Synthesis and molecular structure

The mononuclear cations of the general formula [(η⁶-arene)RuCl(pdpt)]⁺ (pdpt = 5,6-diphenyl-3-(pyridine-2-yl)-1,2,4-triazine; arene = C₆H₆ (1); C₆H₅Me (2); p-PrⁱC₆H₄Me (3); C₆Me₆ (4)) have been synthesised from 5,6-diphenyl-3-(pyridine-2-yl)-1,2,4-triazine (pdpt) and the corresponding chloro complexes [(η⁶-C₆H₆)Ru(μ-Cl)Cl]₂, [(η⁶-C₆H₅Me)Ru(μ-Cl)Cl]₂, [(η⁶p-PrⁱC₆H₄Me)Ru(μ-Cl)Cl]₂ and [(η⁶-C₆Me₆)Ru(μ-Cl)Cl]₂, respectively. The X-ray crystal structure analyses of [1][PF₆] · (C₆H₆)_2.5 and [2][PF₆] · (CH₃CN)₂ reveal a typical piano-stool geometry around the metal centre and in the crystal packing a complexed networks of intermolecular interactions.     

[RuIII(medtra)(H2O)] (medtra = N-methylethylenediaminetriacetate) complex – A highly efficient NO inhibitor with low toxicity

Stopped-flow kinetic measurements were used to compare the reactivities of [Ru(medtra)(H₂O)] (medtra³⁻ = N-methylethylenediaminetriacetate) (1) and [Ru(hedtra)(H₂O)] (2) (hedtra³⁻ = N-hydroxyethylethylenediaminetriacetate) with NO in aqueous solution at 15 °C, pH 7.2 (phosphate buffer). The measured second-order rate constants (3 × 10³ and 6 × 10⁴ M⁻¹ s⁻¹ for 1 and 2, respectively) are three to four order of magnitudes lower than that for the reaction between [Ru^III(edta)(H₂O)]⁻ (3) with NO. However, NO scavenging studies of complexes 1–3, conducted by measuring the difference in nitrite production between treated and untreated murine macrophage cells, revealed that despite being less kinetically reactive toward NO, the [Ru(medtra)(H₂O)] complex exhibited the highest NO scavenging ability and lowest toxicity of compounds 1–3.     

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.     

Two new pseudohalide-bridged Cu(II) complexes with a hydrazone ligand: Syntheses,crystal structures and magnetic studies

Two new pseudohalide-bridged copper(II) complexes [{Cu(PBH)(μ_1,1-CNO)}₂] (1) and {Cu(PBH)(μ_1,5-NCNCN)}_n (2) (where HPBH = 2-pyridinecarboxaldehyde benzoyl hydrazone) have been synthesised and characterised by elemental analysis, CV, IR and UV–Vis spectral studies. The tridentate hydrazone pro-ligand (HPBH) was obtained by the condensation of benzhydrazide and pyridine-2-carboxaldehyde. Structures of both complexes have been established by X-ray crystallography which shows that 1 is a μ_1,1-CNO^?-bridged dimer whereas 2 is a μ_1,5-dca-bridged (dca = dicyanamide) linear polynuclear structure. Variable temperature magnetic susceptibility studies indicate weak antiferromagnetic interactions with J values ?0.50 cm^?1 and ?0.10 cm^?1 for 1 and 2, respectively.     

Syntheses,structures, and magnetic properties of heterobimetallic complexes based on tetracyanometallic building blocks

Two tetracyanometalate building blocks, [Fe(5,5′-dmbipy)(CN)₄]^? (2) and [Fe(4,4′-dmbipy)(CN)₄]^? (3) (5,5′-dmbipy = 5,5′-dimethyl-2,2′-bipyridine; 4,4′-dmbipy = 4,4′-dimethyl-2,2′-bipyridine), and two cyano-bridged heterobimetallic complexes, [Cu₂(bpca)₂(H₂O)₂Fe₂(5,5′-dmbipy)₂(CN)₈] · 2[Cu(bpca)Fe(5,5′-dmbipy)(CN)₄] · 4H₂O (4) and [Cu(bpca)Fe(4,4′-dmbipy)(CN)₄]_n (5) (bpca = bis(2-pyridylcarbonyl)amidate), have been synthesized and structurally characterized. Complex 4 contains two dinuclear and one tetranuclear heterobimetallic clusters in an asymmetric unit whereas the structure of complex 5 features a one-dimensional heterobimetallic zigzag chain. The Cu(II) ion is penta-coordinated in the form of a distorted square-based pyramid. Magnetic studies show ferromagnetic coupling between Cu(II) and Fe(III) ions with g = 2.28, J₁ = 2.64 cm^?1, J₂ = 5.40 cm^?1 and TIP = ?2.36 × 10^?3 for complex 4, and g = 2.17, J = 4.82 cm^?1 and zJ′ = 0.029 cm^?1 for complex 5.     

Synthesis,characterization and magnetic properties of six new copper(II) complexes with aminoacids as bridging ligand,exhibiting ferromagnetic coupling

The synthesis, crystallographic analysis and magnetic studies of six new copper(II) complexes of formulae [Cu(μ-ala)(im)(H₂O)]_n(ClO₄)_n (1), [Cu(μ-ala)(pz)(μ-ClO₄)] (2), [Cu(μ-phe)(im)(H₂O)]_n(ClO₄)_n (3), [Cu(μ-gly)(H₂O)(ClO₄)]_n (4), [Cu(μ-gly)(pz)(ClO₄)]_n(5) and [Cu(μ-pro)(pz)(ClO₄)]_n (6) have been carried out (ala = alanine; phe = phenylalanine; gly = glycine; pro = proline; im = imidazole; pz = pyrazole). In all cases, the deprotonated aminoacid ligand acts as chelate through the N(amine) and one O(carboxylato), whereas the second O atom of the same carboxylato acts as a bridge to the neighbouring copper(II) ion. The coordination of copper(II) ions is square-pyramidal in all complexes but 2 (elongated O_h). All complexes (1–6) are uniform chains with syn–anti (equatorial–equatorial) coordination mode of the carboxylato bridging ligand, exhibiting intrachain ferromagnetic interactions.     

Synthesis,structures and characterization of the dinuclear nickel(II) complexes containing N,N,N′,N′-tetrakis[(1-ethyl-2-benzimidazolyl)methyl]-2-hydroxy-1,3-diaminopropane and an azide ion

Two dinuclear nickel(II) complexes, [Ni₂(L-Et)(N₃)(H₂O)₃](NO₃)₂ · 2H₂O (1) and [Ni₂(L-Et)(μ-1,3-N₃)(H₂O)₂](NO₃)₂ · 4H₂O (2) containing (HL-Et = N,N,N′,N′-tetrakis[(1-ethyl-2-benzimidazolyl)methyl]-2-hydroxy-1,3-diaminopropane), have been synthesized and characterized by their IR and UV–Vis spectra and magnetic susceptibilities. The crystal structures of [Ni₂(L-Et)(N₃)(H₂O)₃](NO₃)₂ · CH₃OH (1′) and [Ni₂(L-Et)(μ-1,3-N₃)(H₂O)₂](NO₃)₂ · 2C₂H₅OH (2′) similar to 1 and 2 were determined by X-ray crystallography. In 1′, the two nickel(II) ions are bridged by only an alkoxo group of L-Et⁻, while an azido and an alkoxo connect two nickel(II) ions in 2′. Magnetic susceptibility measurements (2–300 K) showed a weak ferromagnetic exchange coupling between the two nickel(II) ions (2J = 10.1 cm⁻¹) for 1. On the other hand, antiferromagnetic interactions were observed for 2 (2J = −15.8 cm⁻¹).     

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.     

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.     

Synthesis and biological study of 3-(phenylsulfonyl)thieno[2,3-e][1,2,3]triazolo[1,5-a]pyrimidines as potent and selective serotonin 5-HT6 receptor antagonists

A number of 3-(phenylsulfonyl)thieno[2,3-e][1,2,3]triazolo[1,5-a]pyrimidines were prepared and their 5-HT₆ receptor binding affinity and ability to inhibit the functional cellular responses to serotonin were evaluated. 3-[(3-Chlorophenyl)sulfonyl]-N-(tetrahydrofuran-2-ylmethyl)thieno[2,3-e][1,2,3]triazolo[1,5-a]pyrimidin-5-amine 2{5,26} appeared to be the most active in a functional assay (IC₅₀ = 29.0 nM) and 3-(phenylsulfonyl)-N-(2-thienylmethyl) thieno[2,3-e][1,2,3]triazolo[1,5-a]pyrimidin-5-amine 2{1,28} demonstrated the greatest affinity in a 5-HT₆ receptor radioligand binding assay (K_i = 1.7 nM). A screening of 5-HT_2A and 5-HT_2B receptor affinity revealed that 3-(phenylsulfonyl)thieno[2,3-e][1,2,3]triazolo[1,5-a]pyrimidines are highly selective 5-HT₆ receptor ligands.     

Design,modification and 3D QSAR studies of novel 2,3-dihydrobenzo[b][1,4]dioxin-containing 4,5-dihydro-1H-pyrazole derivatives as inhibitors of B-Raf kinase

Two series of novel 2,3-dihydrobenzo[b][1,4]dioxin-containing 4,5-dihydro-1H-pyrazole derivatives C1–C15 and D1–D15 have been synthesized and evaluated for their B-Raf inhibitory and anti-proliferation activities. Compound C14 ((3-(4-bromophenyl)-5-(2-fluorophenyl)-4,5-dihydro-1H-pyrazol-1-yl)(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methanone) showed the most potent biological activity against B-Raf^V600E (IC₅₀ = 0.11 μM) and WM266.4 human melanoma cell line (GI₅₀ = 0.58 μM), being comparable with the positive control Erlotinib and more potent than our previous best compound, while D10 ((2,3-dihydrobenzo[b][1,4]dioxin-2-yl)(5-(3-fluorophenyl)-3-phenyl-4,5-dihydro-1H-pyrazol-1-yl)methanone) performed the best in the D series (IC₅₀ = 1.70 μM; GI₅₀ = 1.45 μM). The docking simulation was performed to analyze the probable binding models and poses and the QSAR model was built for reasonable design of B-Raf inhibitors in future. The introduction of 2,3-dihydrobenzo[b][1,4]dioxin structure reinforced the combination of our compounds and the receptor, resulting in progress of bioactivity.     

Influence of ligands on the fac⇌Δhνmer isomerization in [RuCl3(NO)(P–P)] complexes, [P–P = R2P(CH2)nPR2 (n = 1–3) and R2P(CH2)POR2, PR2–CHCH–PR2, R = Ph and (C6H11)2P-(CH2)2-P(C6H11)2]

[RuCl₃(NO)(P–P)], [P–P = R₂P(CH₂)_nPR₂ (n = 1–3) and R₂P(CH₂)POR₂, PR₂–CHCH–PR₂, R = Ph and (C₆H₁₁)₂P-(CH₂)₂-P(C₆H₁₁)₂] were obtained and characterized by ³¹P {¹H} NMR, IR spectroscopies and cyclic voltammetry. The structures of fac-[RuCl₃(NO)(P–P)], P–P = dppm (1), dppe (2), c-dppen (3) and dppp (4), mer-[RuCl₃(NO)(dcpe)] (6a) and mer-[RuCl₃(NO)(dppmO)] (7) have been determined by X-ray diffraction. Photochemical isomerization of fac- to mer-[RuCl₃(NO)(P–P)] was observed under white light in a CH₂Cl₂ solution and in solid state. The isomerization processes were followed by IR and ³¹P {¹H} spectra. The mer-[RuCl₃(¹⁵NO)(dppb)] isomer was used for the definition of the phosphorus atoms in the structure of the complex in solution. The electrochemical study shows that the oxidation/reduction processes observed in these complexes are dependent on both the isomer (fac or mer) and the solvent. In CH₂Cl₂, the NO⁺ reduction potentials are less negative for the mer-isomers than for the fac ones, while in CH₃CN solvent these potentials are, in general, very close for both isomers.     

Synthesis and evaluation of novel azetidine analogs as potent inhibitors of vesicular [3H]dopamine uptake

Lobelane analogs that incorporate a central piperidine or pyrrolidine moiety have previously been reported by our group as potent inhibitors of VMAT2 function. Further central ring size reduction of the piperidine moiety in lobelane to a four-membered heterocyclic ring has been carried out in the current study to afford novel cis-and trans-azetidine analogs. These azetidine analogs (15a–15c and 22a–22c) potently inhibited [³H]dopamine (DA) uptake into isolated synaptic vesicles (K_i ? 66 nM). The cis-4-methoxy analog 22b was the most potent inhibitor (K_i = 24 nM), and was twofold more potent that either lobelane (2a, K_i = 45 nM) or norlobelane (2b, K_i = 43 nM). The trans-methylenedioxy analog, 15c (K_i = 31 nM), was equipotent with the cis-analog, 22b, in this assay. Thus, cis- and trans-azetidine analogs 22b and 15c represent potential leads in the discovery of new clinical candidates for the treatment of methamphetamine abuse.     

Metal-assisted preparation of the alkenyl ketone and carbonyl complexes from 1-alkyne and H2O: C–C triple bond cleavage of terminal alkyne

Reactions of Cp*RhCl₂(PPh₃) (1) with 1-alkyne and H₂O in the presence of KPF₆ generated alkenyl ketone complexes [Cp*Rh(CRCHCOCH₂R)(PPh₃)](PF₆) (2) (R = Ph (a), C₆H₄−p-Me (b), C₆H₄-p-COOMe (c), C₆H₄-p-NO₂ (d)). A similar complex [Cp*Rh(CPhCHCOCH₂Ph)(PMePh₂)](PF₆) (2e) was obtained by use of Cp*RhCl₂(PMePh₂). It was revealed by X-ray analyses of 2b, 2c and 2e that the complexes 2 consist of the five-membered ring structures bound by the carbon and oxygen atoms of the alkenyl ketone group. Similar reactions of Cp*IrCl₂(PPh₃) (6) or (C₆Me₆)RuCl₂(PPh₃) (7) proceeded with a cleavage of C–C triple bond of 1-alkyne without formation of an alkenyl ketone complex, affording the corresponding carbonyl complexes, [Cp*IrCl(PPh₃)(CO)](PF₆) (8) or [(C₆Me₆)RuCl(PPh₃)(CO)](PF₆) (9). The diphosphine complexes [(Cp*MCl₂)₂{μ-diphos}] (4: M = Rh, diphos = dppm,; 12a: M = Ir, diphos = dppm; 12b: M = Ir, diphos = dppb) gave a Cl-bridged rhodium complex [{Cp*Rh(μ-Cl)}₂{μ-dppm}](PF₆)₂ (5), mono-carbonyl or dicarbonyl iridium complexes,[(Cp*IrCl₂){μ-dppm}{Cp*IrCl(CO)}](PF₆)(13a) or [{Cp*IrCl(CO)}₂{μ-dppb}](PF₆)₂ (14b), respectively.     

Structure-based discovery of cellular-active allosteric inhibitors of FAK

In order to develop potent and selective focal adhesion kinase (FAK) inhibitors, synthetic studies on pyrazolo[4,3-c][2,1]benzothiazines targeted for the FAK allosteric site were carried out. Based on the X-ray structural analysis of the co-crystal of the lead compound, 8-(4-ethylphenyl)-5-methyl-1,5-dihydropyrazolo[4,3-c][2,1]benzothiazine 4,4-dioxide 1 with FAK, we designed and prepared 1,5-dimethyl-1,5-dihydropyrazolo[4,3-c][2,1]benzothiazin derivatives which selectively inhibited kinase activity of FAK without affecting seven other kinases. The optimized compound, N-(4-tert-butylbenzyl)-1,5-dimethyl-1,5-dihydropyrazolo[4,3-c][2,1]benzothiazin-8-amine 4,4-dioxide 30 possessed significant FAK kinase inhibitory activities both in cell-free (IC₅₀ = 0.64 μM) and in cellular assays (IC₅₀ = 7.1 μM). These results clearly demonstrated a potential of FAK allosteric inhibitors as antitumor agents.     

Diversity of triflate coordination modes in neodymocene complexes containing bulky bis(trimethylsilyl)cyclopentadienyl ligands

The reaction of Nd(OTf)₃ (OTf = O₃SCF₃) with two molar equivalents of LiCp″ [Cp″ = C₅H₃(SiMe₃)₂-1,3] in thf solution generated the blue, tetrametallic dimer [{Nd(η⁵-Cp″)₂(μ₂-κ²-O₃SCF₃)(μ₃-κ³-O₃SCF₃)Li(thf)}₂] (1a), which has been shown by X-ray crystallography to contain a tricyclic, ladder-like scaffold with Nd and Li cations and OTf anions at its core. Compound 1a was relatively labile, being readily cleaved by a variety of donor molecules. 18-Crown-6 efficiently encapsulated the lithium cation to yield the salt [Li(18-crown-6)][Nd(η⁵-Cp″)₂(κ¹-O₃SCF₃)(κ²-O₃SCF₃)] (2). Addition of N,N,N′,N′-tetramethylethylenediamine (tmeda) afforded the monomeric bimetallic [Nd(η⁵-Cp″)₂(μ₂-κ²-O₃SCF₃)₂Li(tmeda)] (3), while the more rigid donor 2,2′-bipyridine (bipy) produced the neutral, Li-free complex [Nd(η⁵-Cp″)₂(κ¹-O₃SCF₃)(bipy)] (4). The molecular and crystal structures of 2–4, as well as that of1b, the unstable La analogue of 1a, have been determined by X-ray methods.