Synthesis and Photobiological Activity of Ru(II) Dyads Derived from Pyrrole-2-carboxylate Thionoesters.

The synthesis and characterization of a series of heteroleptic ruthenium(II) dyads derived from pyrrole-2-carboxylate thionoesters are reported. Ligands bearing a conjugated thiocarbonyl group were found to be more reactive toward Ru(II) complexation compared to analogous all-oxygen pyrrole-2-carboxylate esters, and salient features of the resulting complexes were determined using X-ray crystallography, electronic absorption, and NMR spectroscopy. Selected complexes were evaluated for their potential in photobiological applications, whereupon all compounds demonstrated in vitro photodynamic therapy effects in HL-60 and SK-MEL-28 cells, with low nanomolar activities observed, and exhibited some of the largest photocytotoxicity indices to date (>2000). Importantly, the Ru(II) dyads could be activated by relatively soft doses of visible (100 J cm-2, 29 mW cm-2) or red light (100 J cm-2, 34 mW cm-2), which is compatible with therapeutic applications. Some compounds even demonstrated up to five-fold selectivity for malignant cells over noncancerous cells. These complexes were also shown to photocleave, and in some cases unwind, DNA in cell-free experiments. Thus, this new class of Ru(II) dyads has the capacity to interact with and damage biological macromolecules in the cell, making them attractive agents for photodynamic therapy.

Synthesis, Characterization, and Properties of Weakly Coordinating Anions Based on tris-Perfluoro-tert-Butoxyborane.

A convenient method for the preparation of strongly Lewis acidic tris-perfluoro-tert-butoxyborane B(ORF)3 (1), (ORF = OC(CF3)3) was developed, and its X-ray structure was determined. 1 was used as a precursor, guided by density functional theory (DFT) calculations and volume-based thermodynamics, for the synthesis of [NEt4][NCB(ORF)3] (3) and [NMe4][FB(ORF)3] (5) and the novel large and weakly coordinating anion salts [Li 15-Crown-5][B(ORF)4] (2) and [NEt4][CN{B(ORF)3}2] (4). The stability of [B(ORF)4]- was compared with that of some related known weakly coordinating anions by appropriate DFT calculations.

Deuteration and tautomeric reactivity of the 1-methyl functionality of free-base dipyrrins.

Regioselective reactivity of the 1-methyl group of free-base dipyrrins is explored, including discussion of tautomerism to provide exocyclic alkenyl reactivity. Deuterium is installed so as to generate dipyrrins substituted with deuterated methyl groups. Furthermore, the 1-methyl group reacts to become involved in C-C bonds involving only sp3-hybridised carbon atoms. The isolation of an elusive framework featuring a dipyrrin substituted with a pyrrole in a non-vinylogous fashion is also reported. The use of asymmetric dipyrrins featuring an electron-withdrawing group on one of the pyrrolic units results in regioselective reaction of the alpha-methyl group distal to the electron-withdrawing group.

Access to Substituted Dihydrothiopyrano[2,3-b]indoles via Sequential Rearrangements During S-Alkylation and Au-Catalyzed Hydroarylation on Indoline-2-thiones.

An efficient methodology for the synthesis of indole-fused dihydrothiopyrans has been developed from indoline-2-thiones. The protocol involves the synthesis of conjugated ene-yne-substituted indole-sulfides, a gold(III)-catalyzed rearrangement of the ene-yne side chain followed by intramolecular hydroarylation via C3-H functionalization of the indole core. This new synthesis of functionalized tricyclic indole derivatives through sequential rearrangements is quite general in nature.

Aza-Diels-Alder reaction between N-aryl-1-oxo-1H-isoindolium ions and tert-enamides: Steric effects on reaction outcome.

The synthesis of 5-substituted 6,6a-dihydroisoindolo[2,1-a]quinolin-11(5H)-ones via [4 + 2] imino-Diels-Alder cyclization from N-aryl-3-hydroxyisoindolinones and N-vinyl lactams under Lewis acid-catalysed anhydrous conditions is reported. Reactions of N-(2-substituted-aryl)-3-hydroxyisoindolinones with N-vinylpyrrolidone under identical conditions resulted in the formation of 2-(2-substitued-aryl)-3-(2-(2-oxopyrrolidin-1-yl)vinyl)isoindolin-1-one analogues indicating steric hinderance as the cause of deviation. The probable mechanism of the reaction based on the results from X-ray crystallography and molecular modelling is discussed.

Reactions of a cyclodimethylsiloxane (Me2SiO)6 with silver salts of weakly coordinating anions; crystal structures of [Ag(Me2SiO)6][Al] ([Al] = [FAl{OC(CF3)3}3], [Al{OC(CF3)3}4]) and their comparison with [Ag(18-crown-6)]2[SbF6]2.

Two silver-cyclodimethylsiloxane cation salts [AgD6][Al] ([Al] = [Al(ORF)4](1) or [FAl(OR(F))3](2), R(F) = C(CF3)3, D = Me2SiO) were prepared by the reactions of Ag[Al] with D6 in SO2(l). For a comparison the [Ag(18-crown-6)]2[SbF6]2(3) salt was prepared by the reaction of Ag[SbF6] and 18-crown-6 in SO2(l). The compounds were characterized by IR, multinuclear NMR, and single crystal X-ray crystallography. The structures of 1 and 2 show that D6 acts as a pseudo crown ether toward Ag(+). The stabilities and bonding of [MDn](+) and [M(18-crown-6)](+) (M = Ag, Li, n = 4-8) complexes were studied with theoretical calculations. The calculations predicted that D6 adopts a puckered C(i) symmetric structure in the gas phase in contrast to previous reports. 18-Crown-6 was calculated to bind more strongly to Li(+) and Ag(+) than D6. (29)Si[(1)H] NMR results in solution, and calculations in the gas phase established that a hard Lewis acid Li(+) binds more strongly to D6 than Ag(+). A comparison of the [MD(n)](+) complex stabilities showed D7 to form the most stable metal complexes in the gas phase and the solid state and explained why [AgD7][SbF6] was isolated in a previous reaction where ring transformations resulted in an equilibrium of [AgD(n)](+) complexes. In contrast, the isolations of 1 and 2 were possible because the corresponding equilibrium of [AgD(n)](+) complexes was not observed with [Al](-) anions. The formation of the dinuclear complex salt 3 instead of the corresponding mononuclear complex salt was shown to be driven by the gain in lattice enthalpy in the solid state. The bonding to Li(+) in D6 and 18-crown-6 metal complexes was described by a quantum theory of atoms in molecules (QTAIM) analysis to be mostly electrostatic while the bonding to Ag(+) also had a significant charge transfer component. The charge transfer from both D6 and 18-crown-6 to Ag(+) and Li(+) metal ions was depicted by the QTAIM analysis to be of similar strength, and the difference in the stabilities of the complexes was attributed mostly to more attractive electrostatic interactions between 18-crown-6 and the metal ions despite the more negative oxygen atomic charges calculated for D6.

Bronsted acid-catalyzed rapid enol-ether formation of 2-hydroxyindole-3-carboxaldehydes.

A one-step Bronsted acid-catalyzed synthetic methodology leading to 3-(alkoxymethylene)indolin-2-ones was developed starting from easily accessible 2-hydroxyindole-3-carboxaldehydes. The procedure simply involves a treatment of differently substituted 2-hydroxyindole-3-carboxaldehydes with various alcohols (primary/secondary/tertiary/allyl/propargyl/benzyl) in the presence of a catalytic amount of Bronsted acids such as [Formula: see text]-toluenesulfonic acid and trifluroacetic acid. A series of 19 indolin-2-one-based enol-ethers were synthesized in excellent yields, which implies the general character of our methodology. The enol-ethers produced could be used as a useful building block for the synthesis of indole-based heterocycles.

Use of F-BODIPYs as a protection strategy for dipyrrins: optimization of BF(2) removal.

We recently reported the first general method for the deprotection of 4,4-difluoro-4-bora-3a,4a-diaza-s-indacenes (F-BODIPYs) involving a microwave-assisted procedure for the removal of the BF(2) moiety, and liberation of the corresponding free-base dipyrrin. Further optimization of the reaction has resulted in a more convenient and accessible protocol. The availability of this new methodology enables BF(2)-complexation to be used as a dipyrrin protection strategy. Herein lies a detailed examination of the deprotection reaction, with a view to optimization and gaining mechanistic insight, and its application in facilitating a multistep synthesis of pyrrolyldipyrrins.

(1,5-Diphenyl-thio-carbazonato-κS)trimethyl-tin(IV).

In the title compound, [Sn(C13H11N4S)(CH3)3], the Sn(IV) atom is coordinated by an S atom from the 1,5-diphenyl-thio-carbazonato (L) ligand [Sn-S 2.4710 (6) Å] and by three methyl groups [Sn-C 2.123 (3)-2.130 (2) Å] in a distorted tetra-hedral geometry. The aromatic rings of the L ligand form a dihedral angle of 2.1 (1)°.

Tetra-µ-acetato-κ8 O:O'-bis-[(3-chloro-pyridine-κN)ruthenium(II,III)](Ru-Ru) hexa-fluorido-phosphate 1,2-di-chloro-ethane monosolvate.

The title compound, [Ru2(µ-O2CCH3)4(C5H4ClN)2]PF6·C2H4Cl2, was obtained via a rapid substitution reaction of 3-chloro-pyridine for water in [Ru2(µ-O2CCH3)4(H2O)2]PF6 in 2-propanol and subsequent crystallization from a di-chloro-ethane solution. The cationic diruthenium(II,III) tetra-acetate core lies on a crystallographic inversion center with Ru-Ru and Ru-N bond lengths of 2.2738 (3) and 2.2920 (17) Å, respectively. The Ru-Ru-N bond angle is close to linear at 176.48 (4)°, and a significant π-stacking inter-action of 3.5649 (16) Šis seen between overlapping pyridine rings of adjacent cations.

Synthesis and characterization of fluorescent pyrrolyldipyrrinato Sn(IV) complexes.

A series of neutral, 5-coordinate pyrrolyldipyrrinato Sn(IV) complexes have been synthesized via reaction of a pyrrolyldipyrrin, or its corresponding hydrochloride salt, with dibutyltin or diphenyltin oxide. The complexes are structurally unique in that all three nitrogen atoms of the pyrrolyldipyrrinato ligand bind to the tin center, making these complexes the first examples of pyrrolyldipyrrins behaving as LX(2) ligands. The complexes are highly fluorescent, exhibiting fluorescence quantum yields between 0.28 and 0.61, and display interesting preliminary biological activity.

Chiral induction via the disassembly of diruthenium(II,III) tetraacetate by chiral diphosphines.

[Ru(2)(µ-O(2)CCH(3))(4)(MeOH)(2)](PF(6)) reacts with chiral diphosphines (R,R)- and (S,S)-chiraphos, leading to disassembly and production of the enantiomers Λ-[Ru(η(2)-O(2)CCH(3))(η(2)-(R,R)-chiraphos)(2)](PF(6)) and Δ-[Ru(η(2)-O(2)CCH(3))(η(2)-(S,S)-chiraphos)(2)](PF(6)) in high yield and purity. X-ray crystallography and solid-state circular dichroism (CD) show that only the indicated isomers are present in the solid state. Solution CD measurements also indicate their predominance in solution.

Vinylogous anionic processes in the formation and interconversion of tetracyclic ring systems.

Tandem oxy-Cope and transannular vinylogous aldol reactions and/or vinylogous retro-aldol, conjugate addition, and transannular vinylogous aldol reactions transformed some tricyclic vinyl enones into fused tetracycles under basic conditions. Mesylates derived from similar tetracyclic products underwent efficient skeletal reorganization via transannular ring-opening but then different modes of transannular ring-closure upon treatment with tert-butoxide.

2-Propynyl 2,3,4,6-tetra-O-acetyl-α-D-mannopyranoside.

The 2-propynyl group in the title compound, C(17)H(22)O(10), adopts an exoanomeric conformation, with the acetylenic group gauche with respect to position C1. Comparison of (13)C NMR chemical shifts from solution and the solid state suggest that the acetylenic group also adopts a conformation anti to C1 in solution. The pyranose ring adopts a (4)C(1) conformation. Of the three secondary O-acetyl groups, that on position O4, flanked by two equatorial groups, adopts a syn conformation, in agreement with recent generalizations [González-Outeiriño, Nasser & Anderson (2005). J. Org. Chem. 70, 2486-2493]. The acetyl group on position O3 adopts a gauche conformation, also in agreement with the recent generalizations, but that on position O2 adopts a syn conformation, not in agreement with the recent generalizations.

Preparation and characterization of (CNSSS)2(A)2 (A = AsF6(-), SbF6(-), Sb2F11(-)) containing the O2-like 5,5'-bis(1,2,3,4-trithiazolium) dication: the second example of a simple nonsterically hindered main-group diradical that retains its paramagnetism in the solid state.

The reaction of NC-CN with a 1:1 mixture of S(4)(MF(6))(2) and S(8)(MF(6))(2) (M = As, Sb) (stoichiometrically equivalent to four "S(3)MF(6)" units) results in the quantitative formation of S(3)NCCNS(3)(MF(6))(2) [7(MF(6))(2)], which is the thermodynamic sink in this reaction. The Sb(2)F(11)(-) salt 7(Sb(2)F(11))(2) is prepared by the addition of an excess of SbF(5) to 7(AsF(6))(2). Crystal structure determinations for all three salts show that 7(2+) can be viewed as two R-CNS(3)(+) radical cations joined together by a C-C single bond. The two rings are coplanar and in a trans orientation due to electrostatic N(delta-)...S(delta+) interactions. The classically bonded alternative (quinoidal structure), in which the octet rule is obeyed, is not observed and is much higher in energy based on calculated estimates and a simple comparison of pi bond energies. Calculated molecular orbitals (MOs) support this, showing that the MO corresponding to the quinoidal structure lies higher in energy than the nearly degenerate singly occupied MOs of 7(2+). The vibrational spectra of 7(2+) in all salts were assigned based on a normal-coordinate analysis and theoretical vibrational frequencies calculated at the PBE0/6-31G* level. In the solid state, 7(2+) is a planar disjoint diradical with essentially degenerate open-shell singlet and triplet states. The disjoint nature of the diradical cation 7(2+) is established by magnetic susceptibility studies of the Sb(2)F(11)(-) salt doped in an isomorphous diamagnetic host material (CNSNS)(2)(Sb(2)F(11))(2) [10(Sb(2)F(11))(2)]. Intramolecular spin coupling is extremely weak corresponding to a singlet-triplet gap (DeltaE(ST) = 2J) of <+/-2 cm(-1). CASPT2[12,12]/6-311G* calculations support a triplet ground state with a small singlet-triplet gap. The single-crystal electron paramagnetic resonance (EPR) of 7(Sb(2)F(11))(2) doped in 10(Sb(2)F(11))(2) is in agreement with the triplet state arising from the weak coupling between the unpaired electrons residing in p(pi) orbitals in each of the rings. Variable-temperature susceptibility data for bulk samples of 7(A)(2) (A = SbF(6)(-), AsF(6)(-), Sb(2)F(11)(-)) are analyzed by employing both 1D chain and 2D sheet magnetic models. These studies reveal significant intermolecular exchange approximating that of a 1D chain for the SbF(6)(-) salt with |J| = 32 cm(-1). The exchange coupling is on the same order of magnitude as that for the AsF(6)(-) salt, although in this case it is likely that there are complex exchange pathways where no particular one is dominant. Intermolecular exchange in the Sb(2)F(11)(-) salt is an order of magnitude weaker. In solution, the EPR spectrum of 7(2+) shows a broad triplet resonance as well as a sharp resonance that is tentatively attributed to a rotomer of the 7(2+)/anion pair, which is likely the origin of the green species given on dissolution of the red 7(2+) salts in SO(2)/AsF(3)/MF(5). We account for the many similarities between O(2) and 7(2+), which are the only simple nonsterically hindered nonmetal diradicals to retain their paramagnetism in the solid state. 7(2+) is also the first isolable, essentially sulfur-based diradical as evidenced by calculated spin densities.

New synthetic procedures to catena-phosphorus cations: preparation and dissociation of the first cyclo-phosphino-halophosphonium salts.

Chlorination of 1,2,3,4-tetracyclohexyl-cyclo-tetraphosphine (2) by PhICl(2) or PCl(5) in the presence of Me(3)SiOTf or GaCl(3) provides a stepwise approach to salts of the first cyclo-phosphino-chlorophosphonium cations [Cy(4)P(4)Cl](+) ([19](+)) and [Cy(4)P(4)Cl(2)](2+) ([20](2+)). The analogous iodo derivative [Cy(4)P(4)I](+) ([17](+)) is obtained as the tetraiodogallate salt from reaction of 2 with I(2) in the presence of GaI(3). Reactions of the dication [20](2+) with PMe(3) or dmpe effect a dissociation of the cyclic framework resulting in the formation of salts containing [Me(3)PPCyPCyPMe(3)](2+) ([27](2+)), [dmpeCyP](2+) ([29](2+)), and [dmpeCyPCyP](2+) ([30](2+)), respectively. The new cations represent phosphine complexes of the [PCy](2+) and [P(2)Cy(2)](2+) cationic fragments from [20](2+), demonstrating the coordinate nature of the phosphinophosphonium bonds in cyclo-phosphino-halophosphonium cations. The compounds have been characterized by NMR spectroscopy, single crystal X-ray crystallography, and Raman spectroscopy.

Formation of vinylic dipyrroles by the deprotonation of meso-alkyl and meso-benzyl dipyrrin HCl salts.

Under basic conditions, dipyrrin salts bearing alkyl and benzyl groups at the meso-position undergo deprotonation to give vinylic dipyrroles, rather than the corresponding free-base dipyrrins. The deprotonation is reversible and quantitatively returns the dipyrrinato framework under acidic conditions.

12-Eth-oxy-2,3,8,9-tetra-methoxy-benzo[c]phenanthridine dichloro-methane solvate.

The title compound, C(23)H(23)NO(5)·CH(2)Cl(2), was obtained via the alkyl-ation of the 12-hydr-oxy-2,3,8,9-tetra-methoxy-benzo[c]phenanthridine salt. The benzo[c]phenanthridine ring system is essentially planar, with a mean out-of-plane deviation of 0.026 Å. A dicloromethane mol-ecule of solvation is present and located between the sheets of phenanthridine mol-ecules, preventing any significant inter-molecular hydrogen-bonding or π-π inter-actions.

Understanding the electronic structure, reactivity, and hydrogen bonding for a 1,2-diphosphonium dication.

The experimental charge density for hexamethyldiphosphonium ditriflate has been determined from low-temperature high-resolution X-ray diffraction data. These results have been compared with theoretically calculated values for the isolated gas-phase compound. Analysis of the topological and atomic basin properties has provided insight into the exact nature of the P-P bond in both the crystalline and the gas-phase structures. The rho(b)(r) and nabla2rho(b)(r) values highlight the covalent nature of the P-P bond, while the atomic charges indicate a localization of the positive charges on the two phosphorus atoms. This seems to indicate that a covalent bond is formed despite a strong electrostatic repulsion between these two heteroatoms. The topological properties and electrostatic potentials have also been shown to provide significant insight into the chemical reactivity of the title compound. A topological analysis of P2Me4, P2Me5(+), and P2Me6(+2) species has provided information about the progression of the P-P bond in the synthesis of the title compound. An investigation of the different hydrogen-bonding networks present in the crystalline and gas-phase structures, along with their affect on the electronic structure of the title compound has also been investigated. This has all led to significant new insight into the electronic structure, reactivity, and weak hydrogen bonding in prototypical 1,2-diphosphonium dications.

Bifunctional diphosphorus Lewis acids from cyclodiphosphadiazanes.

The quantitative displacement of triflate groups in 1,3-ditriflato-2,4-bis(2,6-dimethylphenyl)cyclodiphospha-2,4-diazane by DMAP (4-dimethylaminopyridine) or Me(3)P gives dicationic complexes containing bifunctional diphosphorus Lewis acceptors.