A Cytotoxic Bis(1,2,3-triazol-5-ylidene)carbazolide Gold(III) Complex Targets DNA by Partial Intercalation.

The syntheses of bis(triazolium)carbazole precursors and their corresponding coinage metal (Au, Ag) complexes are reported. For alkylated triazolium salts, di- or tetranuclear complexes with bridging ligands were isolated, while the bis(aryl) analogue afforded a bis(carbene) AuI -CNC pincer complex suitable for oxidation to the redox-stable [AuIII (CNC)Cl]+ cation. Although the ligand salt and the [AuIII (CNC)Cl]+ complex were both notably cytotoxic toward the breast cancer cell line MDA-MB-231, the AuIII complex was somewhat more selective. Electrophoresis, viscometry, UV-vis, CD and LD spectroscopy suggest the cytotoxic [AuIII (CNC)Cl]+ complex behaves as a partial DNA intercalator. In silico screening indicated that the [AuIII (CNC)Cl]+ complex can target DNA three-way junctions with good specificity, several other regular B-DNA forms, and Z-DNA. Multiple hydrophobic π-type interactions involving T and A bases appear to be important for B-form DNA binding, while phosphate O⋅⋅⋅Au interactions evidently underpin Z-DNA binding. The CNC ligand effectively stabilizes the AuIII ion, preventing reduction in the presence of glutathione. Both the redox stability and DNA affinity of the hit compound might be key factors underpinning its cytotoxicity in vitro.

Synthesis of 6-Membered-Ring Fused Thiazine-Dicarboxylates and Thiazole-Pyrimidines via One-Pot Three-Component Reactions.

A facile and efficient one-pot three-component reaction method for the synthesis of thiazine-dicarboxylates is reported. Reaction of an isocyanide and dialkyl acetylenedicarboxylate with 2-amino-4H-1,3-thiazin-4-one derivatives containing both an acidic proton and an internal nucleophile gave the products in good yields of 76-85%. The reactivity of dialkyl acetylenedicarboxylates was further tested in the synthesis of thiazole-pyrimidines where a two-component reaction of 2-aminothiazole with dialkyl acetylenedicarboxylates was successfully converted to a more efficient three-component reaction of a thiourea, α-haloketone and dialkyl acetylenedicarboxylate (DMAD/DEtAD) to give thiazole-pyrimidines in good yields of 70-91%.

Total synthesis of ent-pavettamine.

Pavettamine, a plant toxin first isolated from Pavetta harborii in 1995, was previously identified as a polyamine with C 2 symmetry and a 1,3-syn-diol moiety on a C10 carbon backbone - one of very few substituted polyamines to be isolated from nature. Its absolute configuration was later established by our first reported total synthesis in 2010. Herein we report the first total synthesis of the enantiomer of pavettamine, ent-pavettamine. The symmetrical structure of the molecule allows for the synthesis of a common C5 fragment that can be divergently transformed into two synthons for later convergent coupling to furnish the target carbon framework. Based on the success of the protocol we employed for the synthesis of the naturally occurring pavettamine, (S)-malic acid was again the starting material of choice for the synthesis of the two individual C5 fragments, with strategic differences in terminal-group manipulation allowing for the synthesis of ent-pavettamine rather than pavettamine. Chain extension and stereoselective ketone reduction were achieved using the (R)-methyl p-tolyl sulfoxide chiral auxiliary to give the desired 1,3-syn-diol C5 unit. A protecting-group strategy was also developed for the orthogonal protection of the alcohol and amine functional groups as they were unveiled. The functionalized C5 fragments were coupled via reductive amination revealing the C10 carbon backbone. Deprotection of the alcohol and amine functional groups successfully provided ent-pavettamine as a TFA salt.

Synthesis and Photophysical Properties of T-Shaped Coinage-Metal Complexes.

The photophysical properties of a series of T-shaped coinage d10 metal complexes, supported by a bis(mesoionic carbene)carbazolide (CNC) pincer ligand, are explored. The series includes a rare new example of a tridentate T-shaped AgI complex. Post-complexation modification of the AuI complex provides access to a linear cationic AuI complex following ligand alkylation, or the first example of a cationic square planar AuIII -F complex from electrophilic attack on the metal centre. Emissions ranging from blue (CuI ) to orange (AgI ) are obtained, with variable contributions of thermally-dependent fluorescence and phosphorescence to the observed photoluminescence. Green emissions are observed for all three gold complexes (neutral T-shaped AuI , cationic linear AuI and square planar cationic AuIII ). The higher quantum yield and longer decay lifetime of the linear gold(I) complex are indicative of increased phosphorescence contribution.

Fischer Carbene Complexes of Iridium(I) for Application in Catalytic Transfer Hydrogenation.

New examples of the very rare class of iridium(I) Fischer carbene complexes (FCCs) are reported from the facile transmetalation from group 6 FCCs. Postcomplexation modification of either the carbene ligand or the ancillary coligands results in a tunable IrI metal center, for unprecedented application as a (pre)catalyst in a benchmark transfer hydrogenation reaction. The introduction of an aminocarbene ligand with a pendant N-donor moiety capable of hemilabile coordination yielded the best catalytic results with turnover frequencies reaching 445 h-1 and requiring 0.1 mol % catalyst and 0.5 mol % base loading, respectively.

The synthesis of a corrole analogue of aquacobalamin (vitamin B12a) and its ligand substitution reactions.

The synthesis of a Co(III) corrole, [10-(2-[[4-(1H-imidazol-1-ylmethyl)benzoyl]amino]phenyl)-5,15-diphenylcorrolato]cobalt(III), DPTC-Co, bearing a tail motif terminating in an imidazole ligand that coordinates Co(III), is described. The corrole therefore places Co(III) in a similar environment to that in aquacobalamin (vitamin B12a, H2OCbl(+)) but with a different equatorial ligand. In coordinating solvents, DPTC-Co is a mixture of five- and six-coordinate species, with a solvent molecule occupying the axial coordination site trans to the proximal imidazole ligand. In an 80:20 MeOH/H2O solution, allowed to age for about 1 h, the predominant species is the six-coordinate aqua species [H2O-DPTC-Co]. It is monomeric at least up to concentrations of 60 µM. The coordinated H2O has a pKa = 9.76(6). Under the same conditions H2OCbl(+) has a pKa = 7.40(2). Equilibrium constants for the substitution of coordinated H2O by exogenous ligands are reported as log K values for neutral N-, P-, and S-donor ligands, and CN(-), NO2(-), N3(-), SCN(-), I(-), and Cys in 80:20 MeOH/H2O solution at low ionic strength. The log K values for [H2O-DPTC-Co] correlate reasonably well with those for H2OCbl(+); therefore, Co(III) displays a similar behavior toward these ligands irrespective of whether the equatorial ligand is a corrole or a corrin. Pyridine is an exception; it is poorly coordinated by H2OCbl(+) because of the sterically hindered coordination site of the corrin. With few exceptions, [H2O-DPTC-Co] has a higher affinity for neutral ligands than H2OCbl(+), but the converse is true for anionic ligands. Density functional theory (DFT) models (BP86/TZVP) show that the Co-ligand bonds tend to be longer in corrin than in corrole complexes, explaining the higher affinity of the latter for neutral ligands. It is argued that the residual charge at the metal center (+2 in corrin, 0 in corrole) increases the affinity of H2OCbl(+) for anionic ligands through an electrostatic attraction. The topological properties of the electron density in the DFT-modeled compounds are used to explore the nature of the bonding between the metal and the ligands.

Di-chlorido-dimethyl-bis-(thio-urea-κS)tin(IV).

The title compound, [Sn(CH3)2Cl2(CH4N2S)2], crystallizes with two half-mol-ecules in the asymmetric unit. Both mol-ecules are completed by inversion symmetry with the two Sn(IV) atoms located on inversion centers. The metal atoms have distorted octa-hedral coordination environments defined by two Cl atoms, two C atoms of methyl groups and two thio-urea S atoms. In the crystal, mol-ecules are linked via N-H⋯Cl and N-H⋯S hydrogen bonds, forming a three-dimensional structure.

Tungsten-183 NMR study of cis-[W(CO)4(PPh3)(4-RC5H4N)]; effect of varying the σ donor strength of the pyridine.

Tungsten-183 NMR data are reported for the complexes cis-[W(CO)4(PPh3)(4-RC5H4N)] (R = H, Me, Ph, COMe, COPh, OMe, NMe2, Cl, NO2). The (183)W chemical shift (obtained by indirect detection using (31)P) is found to correlate with the Hammett σ function for the group R, with (183)W shielding increasing approximately linearly with the donor strength of the pyridine over a range of 93 ppm. The X-ray structures of cis-[W(CO)4(PPh3)(4-MeOC5H4N)] and cis-[W(CO)4(PPh3)(4-PhCOC5H4N)] are also reported.

3-Methyl-1-tosyl-1H-indole-2-carbaldehyde.

The title indole derivative, C(17)H(15)NO(3)S, crystallizes with two independent mol-ecules in the asymmetric unit. The benzene ring of the tosyl group is almost perpedicular to the indole ring in both mol-ecules, with inter-planar angles of 82.60 (5)° and 81.82 (6)°. The two mol-ecules are, as a consequence, able to form an almost centrosymmetric non-bonded dimer, in which the molecules are linked by pairs of C-H⋯π inter-actions. The crystal structure displays a three-dimensional network of C-H⋯O inter-actions. A π-π inter-action occurs between inversion-related indole rings with a centroid-centroid distance of 3.6774 (16) Šand an inter-planar angle of 1.53 (15)°. This inter-action leads to a stacking of mol-ecules along the a axis.

The synthesis of the pyranonaphthoquinones dehydroherbarin and anhydrofusarubin using Wacker oxidation methodology as a key step and other unexpected oxidation reactions with ceric ammonium nitrate and salcomine.

The synthesis of two closely related pyranonaphthoquinones, dehydroherbarin and anhydrofusarubin, is described. The construction of the naphthalene nuclei was achieved using the Stobbe condensation reaction using 2,4-dimethoxybenzaldehyde and 2,4,5-trimethoxybenzaldehyde as their respective starting materials. Two key steps en route include a PIFA-mediated addition of a methoxy substituent onto the naphthalene skeleton and a Wacker oxidation reaction to construct the benzo[g]isochromene nucleus. Two interesting oxidation reactions of the intermediate isochromene enol ether of 7,9-dimethoxy-3-methyl-1H-benzo[g]isochromene-5-ol were observed. Treatment of the substrate with salcomine resulted in the formation of (3-formyl-4-hydroxy-6,8-dimethoxynaphthalene-2-yl)methyl acetate, while treatment of the same substrate with CAN resulted in the formation of racemic (3R,4R)-3-hydroxy-7,9-dimethoxy-3-methyl-5,10-dioxo-3,4,5,10-tetrahydro-1H-benzo[g]isochromen-4-yl nitrate.

Structural study of six cycloalkylammonium cinnamate salt structures featuring one-dimensional columns and two-dimensional hydrogen-bonded networks.

Six ammonium carboxylate salts, namely cyclopentylammonium cinnamate, C(5)H(12)N(+)·C(9)H(7)O(2)(-), (I), cyclohexylammonium cinnamate, C(6)H(14)N(+)·C(9)H(7)O(2)(-), (II), cycloheptylammonium cinnamate form I, C(7)H(16)N(+)·C(9)H(7)O(2)(-), (IIIa), and form II, (IIIb), cyclooctylammonium cinnamate, C(8)H(18)N(+)·C(9)H(7)O(2)(-), (IV), and cyclododecylammonium cinnamate, C(12)H(26)N(+)·C(9)H(7)O(2)(-), (V), are reported. Salts (II)-(V) all have a 1:1 ratio of cation to anion and feature three N(+)-H···O(-) hydrogen bonds forming one-dimensional hydrogen-bonded columns consisting of repeating R(4)(3)(10) rings, while salt (I) has a two-dimensional network made up of alternating R(4)(4)(12) and R(6)(8)(20) rings. Salt (III) consists of two polymorphic forms, viz. form I having Z' = 1 and form II with Z' = 2. The latter polymorph has disorder of the cycloheptane rings in the two cations, as well as whole-molecule disorder of one of the cinnamate anions. A similar, but ordered, Z' = 2 structure is seen in salt (IV).

Helical self-assembly of 2-(1,4,7,10-tetraazacyclododecan-1-yl)cyclohexan-1-ol (cycyclen).

The title macrocyclic amino alcohol compound, C(14)H(30)N(4)O, is investigated as a solid-state synthon for the design of a self-assembled tubular structure. It crystallizes in a helical column constructed by stereospecific O-H···N and N-H···N interactions. The hydrogen-bonding interactions, dependent upon macrocyclic ring helicity and molecular conformation, link R,R and S,S enantiomers in a head-to-tail fashion, forming a continuous hydrophilic inner core.

2-(2-Carb-oxy-eth-yl)-1,3-dioxoisoindoline-5,6-dicarb-oxy-lic acid methanol monosolvate.

In the title compound, C(13)H(9)NO(8)·CH(3)OH, the main mol-ecule possesses three carb-oxy-lic acid groups, which are asymmetrically distributed around the mol-ecule core. This results in hydrogen-bonding motifs ranging from a chain to various rings. The combination of the chain motif together with a carb-oxy-lic dimer R(2) (2)(8) ring motif creates a ribbon of mol-ecules propagating along the c-axis direction. A second ribbon results from the combination of the chain motif together with a methanol solvent mol-ecule and carboxyl-containing R(4) (4)(12) ring motif. These two ribbons combine alternately, forming a hydrogen-bonded layer of mol-ecules parallel to (2[Formula: see text]0).

1-(Anthracen-1-yl)pyrrolidine-2,5-dione.

In the mol-ecular structure of title compound, C(18)H(13)NO(2), the succinimide ring is orientated away from the plane of the anthracene moiety by 71.94 (4)°. The crystal structure features three different types of inter-molecular inter-actions, viz. C-H⋯O, C-H⋯π and π-π bonds. Mol-ecules along the b axis stack on each other as a result of π-π inter-actions which have a centroid-centroid distance of 3.6780 (15) Å, while C-H⋯π inter-actions are present between neigbouring stacks. Also, acting between the stacks are the C-H⋯O inter-actions between the aromatic H atoms of the anthracene and the O atoms of the succinimide.

Cyclo-octanaminium hydrogen succinate monohydrate.

In the title hydrated salt, C(8)H(18)N(+)·C(4)H(5)O(4) (-)·H(2)O, the cyclo-octyl- ring of the cation is disordered over two positions in a 0.833 (3):0.167 (3) ratio. The structure contains various O-H.·O and N-H⋯O inter-actions, forming a hydrogen-bonded layer of mol-ecules perpendicular to the c axis. In each layer, the ammonium cation hydrogen bonds to two hydrogen succinate anions and one water mol-ecule. Each hydrogen succinate anion hydrogen bonds to neighbouring anions, forming a chain of mol-ecules along the b axis. In addition, each hydrogen succinate anion hydrogen bonds to two water mol-ecules and the ammonium cation.

Hexa-kis-(propyl-ammonium) benzene-1,2,4,5-tetra-carboxyl-ate 2,5-dicarb-oxy-benzene-1,4-carboxyl-ate tetra-hydrate.

The title organic salt, 6C(3)H(10)N(+)·C(10)H(2)O(8) (4-)·C(10)H(4)O(8) (2-)·4H(2)O, contains seven independent entities in the asymmetric unit which comprises three propyl-ammonium cations, two water mol-ecules, half a 2,5-dicarb-oxy-benzene-1,4-carboxyl-ate dianion (H(2)btc(2-)) and half a benzene-1,2,4,5-tetra-carboxyl-ate tetra-anion (btc(4-)), the latter two anions being located about centres of inversion. One of the water mol-ecules is disordered over two positions in a 0.55 (2):0.45 (2) ratio. The combination of mol-ecular ions and water mol-ecules results in an extensive and complex three-dimensional network of hydrogen bonds, the network being made up of nine unique N-H⋯O inter-actions between the ammonium cations and the anions, as well as four unique O-H⋯O inter-actions between the water mol-ecules and the anions.

N-[(2Z,4Z)-4-Benzyl-idene-6-chloro-1,4-dihydro-pyrido[2,3-d][1,3]thia-zin-2-yl-idene]benzamide.

In the crystal structure of the title compound, C(21)H(14)ClN(3)OS, mol-ecules assemble into inversion dimers via pairs of N-H⋯N hydrogen bonds involving the N-H hydrogen of the thia-zine ring and the N atom of the pyridine ring. There is a close intra-molecular contact [2.570 (2) Å] between the carbonyl O atom of the benzamide and the S atom of the puckered thia-zine ring. The title compound can exist in two tautomeric forms, viz. amino or imino. The observed structure is compatible with the imino form on the basis of observed residual electron density and the two C-N bond lengths of 1.308 (2) and 1.353 (2) Å.

(2-Amino-phen-yl)methanol.

The crystal strucure of the title compound, C(7)H(9)NO, displays N-H⋯O hydrogen bonds which link mol-ecules related by translation along the b axis, and O-H⋯N and further N-H⋯O hydrogen bonds which link mol-ecules related by the 2(1) screw axis along the c axis. The resulting combination is a hydrogen-bonded layer of mol-ecules parallel to (011).

Dicarbon-yl(hexa-methyl-ene-1,3,5,7-tetra-mine-κN(1))(η(5)-penta-methyl-cyclo-penta-dien-yl)iron(II) tetra-fluoridoborate.

In the title compound, [Fe(C(10)H(15))(C(6)H(12)N(4))(CO)(2)]BF(4), the arrangement around the Fe(II) atom corresponds to a three-legged piano stool. The penta-methyl-cyclo-penta-dienyl (Cp*) ligand occupies three coordination sites, while two CO ligands and one N atom of the hexa-methyl-ene-tetra-mine ligand occupy the remaining coordination sites, completing a pseudo-octahedral geometry. Both the complex cation and the BF(4) (-) anion reside on crystallographic mirror planes. The Fe-N bond length is 2.069 (2) and the Fe-Cp*(centroid) distance is 1.7452 (3) Å.