Diaryl triazenes inhibit cytochrome P450 1A1 and 1B1 more strongly than aryl morpholino triazenes.

Several diaryl triazene derivatives were synthesized and tested for their ability to inhibit cytochrome P450 1A1 and 1B1 as a potential means to prevent and treat cancer. These compounds are more planar than their conformational flexible aryl morpholino triazene counterparts that were previously shown to inhibit the above enzymes. As a result, the diaryl triazenes are more likely to exhibit increased binding to the enzyme active sites and inhibit these enzymes more strongly than the aryl morpholino triazenes. The data indicates that the diaryl triazenes inhibit cytochrome P450 1A1 and 1B1 one to two orders of magnitude more strongly than the aryl morpholino triazenes. Furthermore, compounds 8-10 strongly inhibited cytochrome P450 1B1 with IC50 values of 51 nM, 740 nM, and 590 nM respectively. Thus, diaryl triazenes should be further investigated as a potential chemopreventive agent.

Investigating the change in the photophysical properties of a trio of tetraphenylcyclopentadienone derivatives with varied groups on the aromatic rings in the 3- and 4-positions.

Organic compounds with electronic properties, such as a small band gap, are useful in areas ranging from organic field effect transistors to solar cells. Such organic compounds can possess conjugation and/or aromatic systems, with one example being tetraphenylcyclopentadienone and its derivatives. A trio of dramatically coloured tetraphenylcyclopentadienone derivatives with varied substituents on the aromatic rings in the 3- and 4-positions were prepared. Their identities were confirmed using the usual methods, for example 1 H nuclear magnetic resonance (NMR) spectroscopy, and their purity quantified using elemental analysis. The X-ray crystal structure of compound 2 was determined. Its notable structural features involved the cyclopentadienone core with its distinct C-C and C=C bond lengths and its overall nonplanarity, both of which served to mitigate its antiaromatic nature. Chloroform solutions of compounds 2-4 exhibited absorption spectra with three absorption bands at approximately 250, 350, and 500 nm that were assigned to (π)→(π*) transitions. Computational chemistry methods assisted in assigning the observed transitions to a specific molecular orbital combination in the structures of 2-4. Emission in the red end of the visible spectrum (550-625 nm) was observed from chloroform solutions of all three of the prepared compounds.

Aryl morpholino triazenes inhibit cytochrome P450 1A1 and 1B1.

Many cytochrome P450 1A1 and 1B1 (CYP1A1 and CYP1B1) inhibitors, such as resveratrol, have planar, hydrophobic, aromatic rings in their structure and exhibit anti-cancer activity. Aryl morpholino triazenes have similar structural features and in addition contain a triazene unit consisting of three consecutive, conjugated nitrogen atoms. Several aryl morpholino triazenes, including 4-[(E)-2-(3,4,5-trimethoxyphenyl)diazenyl]-morpholine (2), were prepared from a reaction involving morpholine and a diazonium ion produced from different aniline derivatives, such as 3,4,5-trimethoxyaniline. The aryl morpholino triazenes were then screened at 100µM for their ability to inhibit CYP1A1 and CYP1B1 using ethoxyresorufin as the substrate. Triazenes that inhibited the enzymes to less than 80% of the uninhibited enzyme activity were assayed to determine their IC50 value. Compound 2 was the only triazene to inhibit both CYP1A1 and CYP1B1 to the same degree as resveratrol with IC50 values of 10µM and 18µM, respectively. Compounds 3 and 6 selectively inhibited CYP1B1 over CYP1A1 with IC values of 2µM and 7µM, respectively. Thus, aryl morpholino triazenes are a new class of compounds that can inhibit CYP1A1 and CYP1B1 and potentially prevent cancer.

Crystal structure of [N,N'-bis-(4-methyl-phen-yl)-1,2-di-phenyl-ethane-1,2-di-imine-κ(2) N,N']di-chlorido-palladium(II) methanol monosolvate.

The title compound, [PdCl2(C28H24N2)]·CH3OH, was pre-pared from the reaction of PdCl2(DMSO)2 (DMSO is di-methyl sulfoxide) and N,N'-bis-(4-methyl-phen-yl)-1,2-di-phenyl-ethane-1,2-di-imine in methanol. The chelating di-imine core of the title compound deviates slightly from planarity, with an N-C-C-N torsion angle of 5.3 (3)°. Delocalization in the di-imine core is indicated by N-C and C-C bonds that are, respectively, longer and shorter than those found in related nonchelating di-imines. The distorted square-planar coordination environment around the Pd(II) atom is manifested as bond angles that are smaller and larger than 90°, and palladacycle torsion angles of -173.22 (16) and 167.06 (16)°. These deviations are attributed to the small bite angle of 79.13 (8)° of the di-imine chelate. The crystal packing exhibits weak inter-molecular hydrogen-bonding inter-actions involving aromatic H atoms, Cl atoms and inter-calated methanol solvent mol-ecules, defining layers parallel to (010).

The functional group on (E)-4,4'-disubstituted stilbenes influences toxicity and antioxidative activity in differentiated PC-12 cells.

This work probes the relationship between stilbene functional group and biological activity. The biological activity of synthesized stilbenes (E)-4,4'-dicyanostilbene, (E)-4,4'-diacetylstilbene, (E)-4,4'-diaminostilbene, a novel stilbene, 1,1'-(vinylenedi-p-phenylene)diethanol, and (E)-stilbene was assessed at biologically relevant nanomolar concentrations using the MTS cell viability assay in differentiated PC-12 cells under optimal culture conditions and conditions of oxidative stress. Under optimal culture conditions the synthesized stilbene derivatives were found to be non-toxic to cells at concentrations up to 10 µg/ml. To mimic oxidative stress, the activity of these stilbene derivatives in the presence of 0.03% H2O2 was investigated. Stilbene derivatives with electron-withdrawing functional groups were 2-3 times more toxic than the H2O2 control, indicating that they may form toxic metabolites in the presence of H2O2. Fluorescence data supported that stilbene derivatives with electron-withdrawing functional groups, (E)-4,4'-dicyanostilbene and (E)-4,4'-diacetylstilbene, may react with H2O2. In contrast, the stilbene derivative with a strong electron-donating functional group, (E)-4,4'-diaminostilbene, rescued neurons from H2O2-induced toxicity. The DPPH assay confirmed that (E)-4,4'-diaminostilbene is able to scavenge free radicals. These data indicate that the Hammett value of the functional group correlates with the biological activity of (E)-4,4'-disubstituted stilbenes in differentiated PC-12 cells.

2-[(Naphthalen-1-yl-methyl-idene)amino]-5-methyl-phenol.

The title compound, C(18)H(15)NO, is a Schiff base prepared from an acid-catalyzed condensation reaction between 1-naphthaldehyde and 6-amino-m-cresol. Intra-molecular hydrogen bonding occurs via an O-H⋯N inter-action, generating an S(5) ring motif. Neighboring phenol groups participate in inter-molecular hydrogen bonding through an O-H⋯O inter-action, forming chains. The O atom of the phenol group also participates in an intermolecular C-H⋯O interaction with an H atom of one of the naphthalene rings. The C-N=C-C torsion angle between the phenol and naphthalene rings is -179.8 (2)°. Crystal packing involves stacks with the mol-ecules inter-acting through the π-systems of the C=N with both the phenol system and one of the naphthalene rings.

2-(9-Anthrylmethyl-ideneamino)-4-methyl-phenol.

The title compound, C(22)H(17)NO, is a novel Schiff base synthesized via a condensation reaction between 9-anthracenecarboxaldehyde and 2-amino-p-cresol. The asymmetric unit contains two independent mol-ecules that are joined by an O-H⋯OH hydrogen bond. An intra-molecular O-H⋯N hydrogen bond occurs in each mol-ecule. π-stacking about inversion centers was observed between adjacent phenol rings [centroid-centroid distance = 3.850 (2) Å] and adjacent anthracene rings [centroid-centroid distance = 3.834 (2) Å]. The C-N=C-C torsion angles between the phenol and anthracene rings are close to 180° with values of 174.06 (15) and 179.85 (14)°.

N-[4-(Morpholinodiazen-yl)phen-yl]acetamide.

The title compound, C(12)H(16)N(4)O(2), is a member of a family of morpholine-substituted aromatic diazenes. Conjugation of the diazene group π-system and the lone pair of electrons of the morpholine N atom is evidenced by a lengthened N=N double bond of 1.2707 (19) Šand a shortened N-N single bond of 1.346 (2) Å. The bond angles at the morpholine N atom range from 113.52 (14) to 121.12 (14)°, indicating some degree of sp(2) hybridization. The morpholine ring adopts a conventional chair conformation with the diazenyl group in the equatorial position. The diazenyl and acetamido groups are both twisted relative to the plane of the benzene ring by 12.3 (2) and 25.5 (3)°, respectively.

Structures of anhydrous and hydrated copper(II) hexafluoroacetylacetonate.

Crystal structure analyses are reported for anhydrous copper(II) hexafluoroacetylacetonate (Cu(hfac)(2)) and for two of its hydrates. The anhydrous compound (Cu(hfac)(2), 1: P1; at 100 K, a = 5.428(1), b = 5.849(1), c = 11.516(3) A; alpha = 81.47(2), beta = 74.57(2), gamma = 86.96(2) degrees; Z = 1) contains centrosymmetric square-planar complexes with close intermolecular Cu.F contacts. The geometry of the complex is similar to that previously reported for Cu(hfac)(2).toluene. The monoaquo compound (Cu(hfac)(2)(H(2)O), 2: P2(1)/c; at 100 K, a = 10.8300(8), b = 6.5400(6), c = 21.551(3) A; beta = 90.282(8) degrees; Z = 4) consists of square-pyramidal molecules with apical H(2)O ligands, and close-lying F atoms in the sixth coordination sites. The major difference between this structure and the two other polymorphs previously reported is the nature and direction of hydrogen bonds. The yellow-green solid formed from Cu(hfac)(2) with excess H(2)O is identified as the trihydrate. In crystalline form it is the previously unreported [trans-Cu(hfac)(2)(H(2)O)(2)].H(2)O (3: P1; at 150 K, a = 8.3899(3), b = 9.6011(3), c = 11.4852(4) A; alpha = 72.397(2), beta = 79.161(2), gamma = 87.843(2) degrees; Z = 2). There is no conclusive evidence in favor of any solid with the composition Cu(hfac)(2).2H(2)O.

Solution Photophysics, One-Electron Photooxidation, and Photoinitiated Two-Electron Oxidation of Molybdenum(III) Complexes.

Several six-coordinate Mo(III) complexes phosphoresce and undergo photooxidation in room-temperature solution. The phosphorescence of (Me(3)[9]aneN(3))MoX(3) (Me(3)[9]aneN(3) = 1,4,7-trimethyl-1,4,7-triazacyclononane) in CH(3)CN at room temperature occurs with the following maxima, lifetimes, and quantum yields: X = Cl, 1120 nm, 1.0 &mgr;s, and 6.1 x 10(-)(5); X = Br, 1130 nm, 0.80 &mgr;s, and 9.6 x 10(-)(5); and X = I, 1160 nm, 0.40 &mgr;s, and 1.2 x 10(-)(4), respectively. The phosphorescences are assigned to the {(2)E(g), (2)T(1g)} --> (4)A(2g) transition. Solutions of HB(Me(2)pz)(3)Mo(III)Cl(3)(-) Me(2)pzH = 3,5-dimethylpyrazole) in CH(3)CN, and solid MoCl(3)(py)(3) and (Me(3)[9]aneN(3))WCl(3), also phosphoresce. (Me(3)[9]aneN(3))MoX(3) (X = Cl, Br, I) complexes undergo reversible one-electron photooxidation upon irradiation in the presence of acceptors such as TCNE and chloranil. (Me(3)[9]aneN(3))MoX(3) (X = Br, I only) are photooxidized irreversibly to [(Me(3)[9]aneN(3))Mo(IV)X(3)](+) by C(NO(2))(4) in CH(3)CN. In CH(3)CN-H(2)O (1:1 v/v), photoinitiated two-electron oxidation occurs: the primary photoproduct is Mo(IV), which disproportionates spontaneously to form [(Me(3)[9]aneN(3))Mo(V)OX(2)](+).

Electronic Absorption Spectra and Phosphorescence of Oxygen-Containing Molybdenum(IV) Complexes.

Electronic absorption and emission spectra are reported for salts of two oxomolybdenum(IV) cations, [MoOCl(CN-t-Bu)(4)](+) and [MoOCl(Ph(2)PCH(2)CH(2)PPh(2))(2)](+), and for the new Mo(IV) complex [trans-Mo(OCH(3))(2)(CN-t-Bu)(4)](2+). All three ions show absorption bands (lambda(max,abs) 550-570 nm; epsilon 45-120 M(-)(1) cm(-)(1)) attributable to the (1)A(1)[(d(xy)())(2)] --> (1)E[(d(xy)())(1)(d(xz)()(,)(yz)())(1)] (C(4)(v)()) transition, and the last two show weak shoulders in the 700-750 nm range due to the analogous spin-forbidden ((1)A(1) --> (3)E) transition. Phosphorescence (lambda(max,em) 850-960 nm) occurs in the solid state for all three compounds at both room temperature and 77 K, and for [MoOCl(CN-t-Bu)(4)](+) in CH(2)Cl(2) at room temperature. These are the first phosphorescences recorded for molybdenum(IV) complexes. [MoOCl(CN-t-Bu)(4)](BPh(4)) precipitates quickly if NaBPh(4) is added to the Mo(IV) solution prepared from MoCl(5) and tert-butyl isocyanide in CH(3)OH. However, if NaPF(6) is used instead, [trans-Mo(OCH(3))(2)(CN-t-Bu)(4)](PF(6))(2) (formed by reaction of [MoOCl(CN-t-Bu)(4)](+) with methanol) crystallizes over a period of ca. 24 h. The crystal structure of [trans-Mo(OCH(3))(2)(CN-t-Bu)(4)](PF(6))(2) has been determined: C(22)H(42)F(12)MoN(4)O(2)P(2), monoclinic; space group P2(1)/c; a = 9.1538(8) Å, b = 15.709(2) Å, c = 13.456(2) Å; beta = 103.31(1) degrees; Z = 2; R(F) = 0.063, R(w)(F) = 0.056 for 2719 reflections with I > sigma(I).