Hydrophobic π-π stacking interactions and hydrogen bonds drive self-aggregation of luteolin in water.

Luteolin is a flavonoid obtained from different plant species. It is known for its versatile biological activities. However, the beneficial effects of luteolin have been limited to small concentrations as a result of poor water solubility. This study aimed at investigating the hydrophobic interaction and hydration of luteolin towards the improvement of its solubility when used as a drug. We report the aggregation properties of luteolin in water by varying the number of monomers using atomistic molecular dynamics simulation. Results show that the equilibrium structure of luteolin occurs in an aggregated state with different structural arrangements. As the monomers size increase, the antiparallel flipped conformation dominates over T-shaped antiparallel, T-shaped parallel, and antiparallel conformations. The formation of intramolecular hydrogen bonding of 0.19 nm between the keto-enol groups results in hydrophobic characteristics. A larger cluster exhibits slow hydrogen bond dynamics for luteolin-luteolin than luteolin-water interaction. Water structure at large cluster size exhibited slow dynamics and low self-diffusion of luteolin. The existence of hydrophobic π-π and hydrogen bonds between luteolin molecules drives strong self-aggregation resulting in poor water solubility. Breakage of these established interactions would result in increased solubility of luteolin in water.

Study of molybdenum(4+) quinoxalyldithiolenes as models for the noninnocent pyranopterin in the molybdenum cofactor.

A model system for the molybdenum cofactor has been developed that illustrates the noninnocent behavior of an N-heterocycle appended to a dithiolene chelate on molybdenum. The pyranopterin of the molybdenum cofactor is modeled by a quinoxalyldithiolene ligand (S(2)BMOQO) formed from the reaction of molybdenum tetrasulfide and quinoxalylalkyne. The resulting complexes TEA[Tp*MoX(S(2)BMOQO)] [1, X = S; 3, X = O; TEA = tetraethylammonium; Tp* = hydrotris(3,5-dimethylpyrazolyl)borate] undergo a dehydration-driven intramolecular cyclization within quinoxalyldithiolene, forming Tp*MoX(pyrrolo-S(2)BMOQO) (2, X = S; 4, X = O). 4 can be oxidized by one electron to produce the molybdenum(5+) complex 5. In a preliminary report of this work, evidence from X-ray crystallography, electronic absorption and resonance Raman spectroscopies, and density functional theory (DFT) bonding calculations revealed that 4 possesses an unusual asymmetric dithiolene chelate with significant thione-thiolate character. The results described here provide a detailed description of the reaction conditions that lead to the formation of 4. Data from cyclic voltammetry, additional DFT calculations, and several spectroscopic methods (IR, electronic absorption, resonance Raman, and electron paramagnetic resonance) have been used to characterize the properties of members in this suite of five Mo(S(2)BMOQO) complexes and further substantiate the highly electron-withdrawing character of the pyrrolo-S(2)BMOQO ligand in 2, 4, and 5. This study of the unique noninnocent ligand S(2)BMOQO provides examples of the roles that the N-heterocycle pterin can play as an essential part of the molybdenum cofactor. The versatile nature of a dithiolene appended by heterocycles may aid in modulating the redox processes of the molybdenum center during the course of enzyme catalysis.

Spectroscopic and electronic structure studies of a dimethyl sulfoxide reductase catalytic intermediate: implications for electron- and atom-transfer reactivity.

The electronic structure of a genuine paramagnetic des-oxo Mo(V) catalytic intermediate in the reaction of dimethyl sulfoxide reductase (DMSOR) with (CH(3))(3)NO has been probed by electron paramagnetic resonance (EPR), electronic absorption, and magnetic circular dichroism (MCD) spectroscopies. EPR spectroscopy reveals rhombic g- and A-tensors that indicate a low-symmetry geometry for this intermediate and a singly occupied molecular orbital that is dominantly metal centered. The excited-state spectroscopic data were interpreted in the context of electronic structure calculations, and this has resulted in a full assignment of the observed MCD and electronic absorption bands, a detailed understanding of the metal-ligand bonding scheme, and an evaluation of the Mo(V) coordination geometry and Mo(V)-S(dithiolene) covalency as it pertains to the stability of the intermediate and electron-transfer regeneration. Finally, the relationship between des-oxo Mo(V) and des-oxo Mo(IV) geometric and electronic structures is discussed relative to the reaction coordinate in members of the DMSOR enzyme family.

Chalcogenidobis(ene-1,2-dithiolate)molybdenum(IV) complexes (chalcogenide E = O, S, Se): probing Mo≡E and ene-1,2-dithiolate substituent effects on geometric and electronic structure.

New square-pyramidal bis(ene-1,2-dithiolate)MoSe complexes, [Mo(IV)Se(L)(2)](2-), have been synthesised along with their terminal sulfido analogues, [Mo(IV)S(L)(2)](2-), using alkyl (L(C(4)H(8))), phenyl (L(Ph)) and methyl carboxylate (L(COOMe)) substituted dithiolene ligands (L). These complexes now complete three sets of Mo(IV)O, Mo(IV)S and Mo(IV)Se species that are coordinated with identical ene-1,2-dithiolate ligands. The [alkyl substituted Mo(S/Se)(L(C(4)H(8)))(2)](2-) complexes were reported in prior investigations (H. Sugimoto, T. Sakurai, H. Miyake, K. Tanaka and H. Tsukube, Inorg. Chem. 2005, 44, 6927, H. Tano, R. Tajima, H. Miyake, S. Itoh and H. Sugimoto, Inorg. Chem. 2008, 47, 7465). The new series of complexes enable a systematic investigation of terminal chalcogenido and supporting ene-1,2-dithiolate ligand effects on geometric structure, electronic structure, and spectroscopic properties. X-ray crystallographic analysis of these (Et(4)N)(2)[MoEL(2)] (E = terminal chalocogenide) complexes reveals an isostructural Mo centre that adopts a distorted square pyramidal geometry. The M≡E bond distances observed in the crystal structures and the ν(M≡E) vibrational frequencies indicate that these bonds are weakened with an increase in L→Mo electron donation (L(COOMe) < L(Ph) < L(C(4)H(8))), and this order is confirmed by an electrochemical study of the complexes. The (77)Se NMR resonances in MoSeL complexes appear at lower magnetic fields as the selenido ion became less basic from MoSeL(C(4)H(8)), MoSeL(Ph) and MoSeL(COOMe). Electronic absorption and resonance Raman spectroscopies have been used to assign key ligand-field, MLCT, LMCT and intraligand CT bands in complexes that possess the L(COOMe) ligand. The presence of low-energy intraligand CT transition in these MoEL(COOMe) compounds directly probes the electron withdrawing nature of the -COOMe substituents, and this underscores the complex electronic structure of square pyramidal bis(ene-1,2-dithiolate)-Mo(IV) complexes that possess extended dithiolene conjugation.

A Valence Bond Description of Dizwitterionic Dithiolene Character in an Oxomolybdenum-bis(dithione).

Metallo-dithiolene non-innocence is explored in an oxomolybdenum-bis(dithione) complex, [Mo4+O(i-Pr2Pipdt)2Cl][PF6] (where i-Pr2Pipdt is N,N'-piperazine-2,3-dithione), that possesses a piperazine ring as an integral part of the dithiolene ligand. The title complex displays unusual spectroscopic features for a formally reduced Mo(IV) dithiolene complex, namely a low energy metal-to-ligand charge transfer band with appreciable intensity and C-C and C-S stretching frequencies that are markedly different from those of oxomolydenum complexes coordinated to dianionic dithiolene ligands. The electronic structure of the ligand has been described in valence bond terms as a resonance hybrid of dithione and dizwitterionic dithiolene contributing structures.

Noninnocent dithiolene ligands: a new oxomolybdenum complex possessing a donor-acceptor dithiolene ligand.

A new monoanionic dithiolene ligand is found in Tp*MoO(S(2)BMOQO). A combination of X-ray crystallography, electronic absorption spectroscopy, resonance Raman spectroscopy, and bonding calculations reveal that the monoanionic dithiolene ligand possesses considerable thiolate-thione character resulting from an admixture of an intraligand charge transfer excited state into the ground state wave function. The unusual dithiolene exhibits a highly versatile donor-acceptor character that dramatically affects the Mo(IV/V) redox couple and points to a potentially noninnocent role of the pterin fragment in pyranopterin Mo enzymes.

Monooxomolybdenum(VI) complexes possessing olefinic dithiolene ligands: probing Mo-S covalency contributions to electron transfer in dimethyl sulfoxide reductase family molybdoenzymes.

A monooxomolybdenum(VI) model complex for the oxidized active site in the DMSOR family of molybdoenzymes has been synthesized and structurally characterized. The compound was obtained from the desoxomolybdenum(IV) derivative by clean oxygen-atom transfer from an amine N-oxide in a manner similar to that observed in the enzyme. A combination of electronic absorption and resonance Raman spectroscopies, coupled with the results of bonding and excited-state calculations, has been used to provide strong support for a highly covalent Mo(d(xy))-S(dithiolene) pi*-bonding interaction in the molybdenum(VI) complex. It is proposed that the resulting Mo-S covalency facilitates electron-transfer regeneration of the catalytically competent DMSOR Mo(IV) active site.