Synthesis and characterization of three group 10 complexes containing nido-carborane diphosphine: [MCl(PPh3){7,8-(PPh2)2-7,8-C2B9H10}] (M = Ni, Pd, Pt)

Three group 10 complexes containing nido-carborane diphosphine, [NiCl(PPh₃){7,8-(PPh₂)₂-7,8-C₂B₉H₁₀}] (1), [PdCl(PPh₃){7,8-(PPh₂)₂-7,8-C₂B₉H₁₀}] · 1.25CH₂Cl₂ (2) and [PtCl(PPh₃){7,8-(PPh₂)₂-7,8-C₂B₉H₁₀}] · 2.5CH₂Cl₂ (3) have been synthesized by the reactions of [M(PPh₃)₂Cl₂] (M = Ni, Pd, Pt) with closo carborane diphosphine 1,2-(PPh₂)₂-1,2-C₂B₁₀H₁₀ in ethanol. For complex 3, it could also be obtained under solvothermal condition. All three complexes were characterized by elemental analysis, FT-IR, ¹H and ¹³C NMR spectroscopy and X-ray structure determination. Single crystal structures show that their structures are similar to each other. In each complex, the nido [7,8-(PPh₂)₂-7,8-C₂B₉H₁₀]⁻, which resulted from the degradation of the initial closo ligand 1,2-(PPh₂)₂-1,2-C₂B₁₀H₁₀ during the reaction process, was coordinated bidentately through the P atoms to M(II) ion, and this resulted in a stable five-membered chelating ring between the bis-diphosphine ligand and the metal. The coordination mode of the metal can be described as a slightly distorted square-planar, in which the remaining two positions were occupied by one Cl⁻ and one PPh₃ group.     

Mono- and bis-cobalt complexes with carbonyl, nitrosyl, and monocarbollide ligands

Reaction of [Co(CO)₃(NO)] with [2-NMe₃-closo-2-CB₁₀H₁₀] in refluxing CH₂Cl₂ affords the mono- and di-cobalt complexes [1-NMe₃-2-CO-2-NO-closo-2,1-CoCB₁₀H₁₀] (3) and [2,7-{Co(CO)(NO)}-7-(μ-H)-1-NMe₃-2-CO-2-NO-closo-2,1-CoCB₁₀H₉] (4), respectively, of which 4 contains formally both Co(I) and Co(-I) centers. Compound 4 reacts with CO to give 3, or with donor ligands L in the presence of Me₃NO to afford simple substituted species, [1-NMe₃-2-L-2-NO-closo-2,1-CoCB₁₀H₁₀] (compounds 5; L = PEt₃, PPh₃, CNBu^t).     

Prochelators triggered by hydrogen peroxide provide hexadentate iron coordination to impede oxidative stress

Prochelators are agents that have little affinity for metal ions until they undergo a chemical conversion. Three new aryl boronate prochelators are presented that are responsive to hydrogen peroxide to provide hexadentate ligands for chelating metal ions. TRENBSIM (tris[(2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzylidene)-2-aminoethyl]amine), TRENBSAM (tris[(2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoyl)-2-aminoethyl]amine), and TB (tris[(2-boronic acid-benzyl)2-aminoethyl]amine) convert to TRENSIM (tris[(salicylideneamino)ethyl]amine), TRENSAM (tris[(2-hydroxybenzoyl)-2-aminoethyl]amine), and TS (tris[2-hydroxybenzyl)2-aminoethyl]amine), respectively. The prochelators were characterized by ¹¹B NMR, and the structures of TRENBSAM, TRENBSIM, and the Fe(III) complex of TS were determined by X-ray crystallography. Of the three prochelator/chelator pairs, TB/TS was identified as the most promising for biological applications, as they prevent iron and copper-induced hydroxyl radical generation in an in vitro assay. TB has negligible interactions with metal ions, whereas TS has apparent binding constants (log K′) at pH 7.4 of 15.87 for Cu(II), 9.67 Zn(II) and 14.42 for Fe(III). Up to 1 mM TB was nontoxic to retinal pigment epithelial cells, whereas 10 μM TS induced cell death. TS protected cells against H₂O₂-induced death, but only within a 1-10 μM range. TB, on the other hand, had a much broader window of protection, suggesting that it may be a useful agent for preventing metal-promoted oxidative damage.     

Modifying aroylhydrazone prochelators for hydrolytic stability and improved cytoprotection against oxidative stress

BSIH ((E)-N′-(2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzylidene)isonicotinohydrazide) is a prodrug version of the metal chelator SIH ((E)-N′-(2-hydroxybenzylidene)isonicotinohydrazide) in which a boronate group prevents metal chelation until reaction with hydrogen peroxide releases SIH, which is then available for sequestering iron(III) and inhibiting iron-catalyzed oxidative damage. While BSIH has shown promise for conditionally targeting iron sequestration in cells under oxidative stress, the yield of SIH is limited by the fact that BSIH exists in cell culture media as an equilibrium mixture with its hydrolysis products isoniazid and 2-formylphenyl boronic acid. In the current study, several BSIH analogs were evaluated for their hydrolytic stability, reaction outcomes with H₂O₂, and prochelator-to-chelator conversion efficiency. Notably, the para-methoxy derivative (p-OMe)BSIH ((E)-N′-(5-methoxy-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzylidene)isonicotinohydrazide) and the meta-, para-double substituted (MD)BSIH ((E)-N′-((6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzo[d][1,3]dioxol-5-yl)methylene)isonicotinohydrazide) showed 1.3- and 1.9-fold improved hydrolytic stability compared to BSIH, respectively, leading to a 22 and 50% increase in chelator released. Moreover, both prochelators were found to protect retinal pigment epithelial cells stressed with either H₂O₂ or paraquat insult.     

Synthesis and characterization of [Co(NO2)2(acac)(IMH2py)] with one-electron-reduced imino nitroxide radical associated with unusual displacement of acetylacetonate in the starting complex trans-Na[Co(NO2)2(acac)2]

A reaction of trans-Na[Co(NO₂)₂(acac)₂] with IM2py(2(2^′-pyridyl)-4,4,5,5-tetramethyl-4,5-dihydro-1H-imidazol-1-oxyl) in methanol afforded trans-[Co(NO₂)₂(acac)(IMH2py)](IMH2py=1-hydroxyl-2(2^′-pyridyl)-4,4,5,5-tetramethyl-4,5-dihydro-1H-imidazole); one-electron reduction of the N-O radical moiety in IM2py and displacement of one of the two acac ligands with retention of two nitrito ligands in the starting complex during the reaction. This new complex was characterized by UV-Vis, ¹H NMR spectra and X-ray analysis.     

Studies on the reactions of ruthenium(II) substrates with tridentate (N,N,O) azo ligands

Reactions of 1-{[2-(arylazo)phenyl]iminomethyl}-2-phenol, HL_sal, 1, [where H represents the dissociable protons upon complexation and aryl groups of HL_sal are phenyl for HL¹_sal, p-methylphenyl for HL²_sal, and p-chlorophenyl for HL³_sal], ligands with Ru(H)(CO)(Cl)(PPh₃)₃ afforded complexes of composition [(L_sal)Ru(CO)(Cl)(PPh₃)] and (L_sal)₂Ru where the N,N,O donor tridentate (L_sal)⁻ ligands coordinated the metal centre facially and meridionally, respectively. Stepwise formation of [(L_sal)₂Ru] has been ascertained. Reaction of 1-{[2-(arylazo)phenyl]iminomethyl}-2-napthol, HL_nap, 2, [where H represents the dissociable protons upon complexation and aryl groups of HL_nap are phenyl for HL¹_nap, p-methylphenyl for HL²_nap, and p-chlorophenyl for HL³_nap], ligands with Ru(H)(CO)(Cl)(PPh₃)₃ afforded exclusively the complexes of composition [(L_nap)Ru(CO)(Cl)(PPh₃)], where N,N,O donor tridentate (L_nap)⁻ was facially coordinated. The ligand 1-{[2-(phenylazo)phenyl]aminomethyl}-2-phenol, HL, 3, was prepared by reducing the aldimine function of HL¹_sal. Reaction of HL with Ru(PPh₃)₃Cl₂ afforded new azosalen complex of Ru(III) in concert with regiospecific oxygenation of phenyl ring of HL. All the new ligands were characterized by analytical and spectroscopic techniques. The complexes were characterized by analytical and spectroscopic techniques and subsequently confirmed by the determination of X-ray structures of selected complexes.     

Synthesis of the manganese-monocarbollide dianion [1-NHBu-2,2,2-(CO)3-closo-2,1-MnCB10H10]: Reactions with transition metal cations

Reaction of [Mn(NCMe)₃(CO)₃][PF₆] with Li₃[7-NHBu^t-nido-7-CB₁₀H₁₀] in THF (THF = tetrahydrofuran) affords the twelve-vertex manganacarborane dianion [1-NHBu^t-2,2,2-(CO)₃-closo-2,1-MnCB₁₀H₁₀]²⁻, isolated as the bis-[N(PPh₃)₂]⁺ salt (5a). This species reacts with {Pt(dppe)}²⁺ (dppe = Ph₂PCH₂CH₂PPh₂) to afford the bimetallic complex [1-NH₂Bu^t-2,3-{Pt(dppe)}-2,2,2-(CO)₃-closo-2,1-MnCB₁₀H₉] (7) which has an Mn-Pt bond. In contrast, with {Cu(PPh₃)}⁺ the anion of 5a yields a CuMnCu trimetallic compound [1-{NH(Bu^t)Cu(PPh₃)}-2,3,7-{Cu(PPh₃)}-3,7-(μ-H)₂-2,2,2-(CO)₃-closo-2,1-MnCB₁₀H₈] (8) in which one of the Cu centers is bonded to Mn, whilst the other is attached to the pendant NHBu^t group. Upon treatment with Ag⁺, compound 5a is oxidized giving the very unusual Mn(III)-carbonyl complex [1,2-μ-NHBu^t-2,2,2-(CO)₃-closo-2,1-MnCB₁₀H₁₀] (9a) in which the carborane ligand formally acts as an eight-electron donor to manganese. The novel structural features of compounds 7, 8, and 9a have been confirmed by X-ray diffraction studies.     

Synthesis, characterization, and evaluation of a novel 99mTc(CO)3 pyrazolyl conjugate of a peptide nucleic acid sequence

The 16-mer peptide nucleic acid sequence H-A GAT CAT GCC CGG CAT-Lys-NH₂ (1), which is complementary to the translation start region of the N-myc oncogene messenger RNA, was synthesized and conjugated to a pyrazolyl diamine bifunctional chelator (pz). The novel conjugate pz-A GAT CAT GCC CGG CAT-Lys-NH₂ (2) was labeled with technetium tricarbonyl, yielding quantitatively the complex fac-[^99mTc(CO)₃(κ³-pz-A GAT CAT GCC CGG CAT-Lys-NH₂)]²⁺ (4). Complex 4 was obtained with high radiochemical purity and high specific activity, revealing high stability in human serum and in cell culture medium. The identity of 4 was confirmed by comparing its reversed-phase high performance liquid chromatography profile with that of the rhenium analog fac-[Re(CO)₃(κ³-pz-A GAT CAT GCC CGG CAT-Lys-NH₂)]²⁺ (3), prepared by conjugation of fac-[Re(CO)₃(3,5-Me₂pz(CH₂)₂N((CH₂)₃COOH)(CH₂)₂NH₂)]⁺ to 1, using solid-phase techniques. UV melting experiments of 1 and 3 with the complementary DNA sequence led to the formation of stable duplexes, indicating that the conjugation of 1 to the pyrazolyl chelator and to the metal fragment fac-[M(CO)₃]⁺ did not affect the recognition of the complementary sequence as well as the duplex stability. For a first screening, SH-SY5Y human neuroblastoma cells, which express N-myc, were treated with 4. The results show that 4 internalizes (7% of the activity goes into the cells, after 4 h at 37 °C), presenting also a relatively high cellular retention (only 40% of internalized activity is released from the cells after 5 h). An erratum to this article can be found at     

Synthesis and structural characterization of zwitterionic oxorhenium(V) complexes with 2-hydroxypyridine

[ReOX₃(PPh₃)₂] complexes (X = Cl and Br) react with equivalent amounts of 2-hydroxypyridine (Hhp) under formation of the mono-substituted, zwitterionic complexes mer-[ReOCl₃(Hhp)(PPh₃)] (1) and mer-[ReOBr₃(Hhp)(PPh₃)] (2). Crystal structure determinations of 1 · CH₂Cl₂ and 2 revealed the Cl and Br ligands adopt a mer arrangement. The Hhp ligands coordinate neutral and monodentate via their exocyclic oxygen atoms in axial positions, trans to the oxo groups. The distorted octahedral coordination sphere of the rhenium(V) complexes is completed by the phosphorus atom of the remaining PPh₃ ligand.     

Syntheses, structures, and magnetic properties of three Fe(II) complexes with reduced radical ligands

Three new Fe(II) complexes [Fe(HIM2py)₂(SCN)₂] (1), [Fe(HIM2py)₂(H₂O)₂](ClO₄)₂ · 2H₂O (2), and [Fe(HIM2py)₂(4,4-bipy)](ClO₄)₂ · 3CH₃CH₂OH (3) (4,4-bipy = 4,4′-bipyridine, HIM2py = 1-hydroxyl-2(2′-pyridyl)-4,4,5,5-tetramethyl-4,5-dihydro-1H-imidazole) have been synthesized and characterized structurally as well as magnetically. The X-ray analysis reveals that HIM2py ligands are coordinated to the metal ions as an unusual six-membered didentate chelate with the κ²N(py), O(HIM) mode. Fe(II) ions in complex 3 are bridged by 4,4-bipy, leading to a 1D chain structure. The magnetic behavior of complex 3 is investigated, showing weak antiferromagnetic interactions.     

Synthesis, structure and magnetic properties of lanthanide(III) complexes with new imidazole-substituted imino nitroxide radical

Synthesis, characterization and magnetic properties of new lanthanide-radical complexes, [Ln^III(hfac)₃(IM2imH)] (Ln = Gd, Tb; IM2imH = 2-(2-pyridyl)-4,5-dihydro-4,4,5,5-tetramethyl-1H-imidazolyl-1-oxy), are described. The molecular structure of the [Tb(hfac)₃(IM2imH)] has been determined by the X-ray diffraction. The magnetic susceptibility data for [Gd(hfac)₃(IM2imH)] show that the Gd-IM2imH magnetic interaction is antiferromagnetic with an exchange coupling constant J = −2.59 cm⁻¹ in contrast to the ferromagnetic interaction in most of Gd(III) complexes containing paramagnetic center, which will be examined in connection with planarity of the IM2imH chelate.     

Synthesis,reactivity and biological activity of N(4)-boronated derivatives of 2′-deoxycytidine

By seeking new stable boron-containing nucleoside derivatives, potential BNCT boron delivery agents, a novel synthetic approach was tested, aimed at a boron attachment via a single bond to an aliphatic carbon of sp³ hybridization. The latter allowed successful modification of deoxycytidine in the reaction with 2-(iodomethyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane of the deoxynucleoside amino group. For new compounds, detailed NMR, LDI HRMS (Laser Desorption/Ionization High-Resolution Mass Spectrometry) analyses along with in vivo phosphorylation studies, toxicity assays and DFT modelling are presented.     

Bioactive metabolites from Alternaria brassicicola ML-P08, an endophytic fungus residing in Malus halliana

A total of 48 strains were isolated from the normal tissues of Malus halliana and the EtOAc extracts of their cultures were subjected to primary antimicrobial screening against four test bacteria and three fungi. As a result, 22 strains exhibited antimicrobial activity against at least one test microbe. Among them, Alternaria brassicicola ML-P08 showing strong activity (MICs: 0.31–2.50 mg/ml) was selected for further investigation on its secondary metabolites. Bioassay-guided fractionation of the EtOAc extract of its liquid culture afforded seven compounds, which were identified as alternariol (1), alternariol 9-methyl ether (2), altechromone A (3), herbarin A (4), cerevisterol (5), 3β,5α-dihydroxy-(22E,24R)-ergosta-7,22-dien-6-one (6) and 3β-hydroxy-(22E,24R)-ergosta-5,8,22-trien-7-one (7), respectively, by spectral means (MS, IR, ¹H- and ¹³C-NMR). In vitro antimicrobial assay showed that compound 3 was substantially active against Bacillus subtilis, Escherichia coli, Pseudomonas fluorescens and Candida albicans with the MICs of 3.9, 3.9, 1.8, and 3.9 μg/ml, respectively. Compound 4 also showed pronounced antifungal activity against Trichophyton rubrum and C. albicans with MICs of both 15.6 μg/ml. In addition, compound 1 exhibited strong xanthine oxidase inhibitory activity with the IC₅₀ of 15.5 μM, comparable to that of positive control, allopurinol (IC₅₀: 10.7 μM).     

Synthesis,X-ray molecular structure analysis,and study on ligand scrambling reactions of new thiolatogold(I) complexes with various phosphines

Treatment of Au(PPh₃)Cl, (AuCl)₂(trans-dpen) and (AuCl)₂(dppfe) with Sn(SPh)(n-Bu)₃ and/or PhSH/KOH affords Au(PPh₃)(SPh) (1), (AuSPh)₂(μ-trans-dpen) (2), (AuSPh)2(μ-dppfe) (3), (AuSPh)(μ-trans-dpen)(AuCl) (4), and (AuSPh)(μ-dppfe)(AuCl) (5) in good yields. All these thiophenolates are characterized by single crystal X-ray analysis, ¹H and ³¹P NMR spectroscopy. 1 forms tetramer through Au⋯Au interaction and π–π interaction between the phenyl group in SPh and one of the phenyl groups in PPh₃ in the solid state. An infinite chain structure is formed for 2 through intermolecular aurophilicity and these chains are connected by partial overlap (π–π interaction) of neighboring phenyl groups in SPh to give two-dimensional networks in the solid state. Similar infinite chains are formed through aurophilicity, but two-dimensional networks are not formed for 4 in the solid state. No multidimensional structure is formed for 3 and 5 in the solid state. ¹H and ³¹P NMR spectroscopy of CDC1₃ solutions of 2, 3, 4, and 5 has revealed that rapid ligand scrambling takes place for 4 and 5.     

Synthesis,characterization, and antimicrobial evaluation of some new hydrazinecarbothioamide, 1,2,4-triazole and 1,3,4-thiadiazole derivatives

In this work, we reported the synthesis and evaluation of antibacterial and antifungal activities of three new compound series obtained from 6-(phenyl/4-chlorophenyl)imidazo[2,1-b]thiazole-3-acetic acid hydrazide: 2-{[6-(phenyl/4-chlorophenyl)imidazo[2,1-b]thiazol-3-yl]acetyl}-N-alkyl/arylhydrazinecarbothioamides (2a–d), 4-alkyl/aryl-2,4-dihydro-5-{[6-(phenyl/4-chlorophenyl)imidazo[2,1-b]thiazol-3-yl]methyl}-3H-1,2,4-triazole-3-thiones (3a–n), and 2-alkyl/arylamino-5-{[6-(phenyl/4-chlorophenyl)imidazo[2,1-b]thiazol-3-yl]methyl}-1,3,4-thiadiazoles (4a–g). The newly synthesized compounds were characterized by IR, ¹H NMR, ¹³C NMR (APT), mass and elemental analysis. Their antibacterial and antifungal activities were evaluated against Staphylococcus aureus ATCC 29213, Pseudomonas aeruginosa ATCC 27853, Escherichia coli ATCC 25922, Candida albicans ATCC 10231, C. parapsilosis ATCC 22019, C. krusei ATCC 6258, Trichophyton mentagrophytes var. erinacei NCPF 375, Microsporum gypseum NCPF 580, and T. tonsurans NCPF 245. 3c, 3f, 3m, 3n, and 4e showed the highest antibacterial activity. Particularly 3c, 3f, 3g, 3k, 3n, 4a, 4e, and 4g showed the highest antifungal activity against tested fungi.     

Synthesis of 5,6-dihydro-4H-1,3-oxazines from neutral and cationic platinum(II) nitrile complexes. X-ray structure of trans-[Pt(CF3){ H2CH2}(PPh3)2]BF4

The 1,3-oxazine complexes cis- and trans-[PtCl₂{ C(R)OCH₂CH₂C}H₂₂] (cis: R=CH₃ (1a), CH₂CH₃ (2a), (CH3)₃C (3a), C₆H₅ (4a); trans:R =CH₃ (1b), C₆H₅ (4b)) were obtained in 51-71% yield by reaction in THF at 0 °C of the corresponding nitrile complexes cis- and trans-[PtCl2(NCR)₂] with 2 equiv. of ⁻OCH₂CH₂CH₂Cl, generated by deprotonation of 3-chloro-1-propanol with n-BuLi. The cationic nitrile complexes trans-[Pt(CF₃)(NCR)(PPh₃)₂]BF₄ (R=CH3, C₆H₅) react with 1 equiv, of ⁻ OCH2CH2CH2Cl to give a mixture of products, including the corresponding oxazine derivatives trans-[Pt(CF₃){ CH₂}(PPh₃)₂]BF₄ (5 and 6), the chloro complex _trans- [Pt(CF₃)Cl(PPh₃)₂] and free oxazine H2. For short reaction times (c. 5–15 min) the oxazine complexes 5 and 6 could be isolated in modest yield (37–49%) from the reaction mixtures and they could be separated from the corresponding chloro complex (yield 40%) by taking advantage of the higher solubility of the latter derivative in benzene. For longer reaction times (> 2 h), trans-[Pt(CF₃)Cl(PPh₃)₂] was the only isolated product. Complex 6 was crystallographically characterized and it was found to contain also crystals of trans- [PtCl{ H₂}(PPh₃)₂]BF₄, which prevented a more detailed analysis of the bond lengths and angles within the metal coordination sphere. The 1,3-oxazine ring, which shows an overall planar arrangement, is characterized by high thermal values of the carbon atoms of the methylene groups indicative of disordering in this part of the molecule in agreement with fast dynamic ring processes suggested on the basis of ¹H NMR spectra. It crystallizes in the trigonal space group P , with a=22.590(4), b=15.970(3) Å, γ=120°, V=7058(1) ų and Z=6. The structure was refined to R=0.059 for 3903 unique observed (I3σ(I)) reflections. A mechanism is proposed for the conversion of nitrile ligands to oxazines in Pt(II) complexes.     

Organometallic indolo[3,2-c]quinolines versus indolo[3,2-d]benzazepines: synthesis, structural and spectroscopic characterization, and biological efficacy

The synthesis of ruthenium(II) and osmium(II) arene complexes with the closely related indolo[3,2-c]quinolines N-(11H-indolo[3,2-c]quinolin-6-yl)-ethane-1,2-diamine (L ¹ ) and N′-(11H-indolo[3,2-c]quinolin-6-yl)-N,N-dimethylethane-1,2-diamine (L ² ) and indolo[3,2-d]benzazepines N-(7,12-dihydroindolo-[3,2-d][1]benzazepin-6-yl)-ethane-1,2-diamine (L ³ ) and N′-(7,12-dihydroindolo-[3,2-d][1]benzazepin-6-yl)-N,N-dimethylethane-1,2-diamine (L ⁴ ) of the general formulas [(η⁶-p-cymene)M^II(L ¹ )Cl]Cl, where M is Ru (4) and Os (6), [(η⁶-p-cymene)M^II(L ² )Cl]Cl, where M is Ru (5) and Os (7), [(η⁶-p-cymene)M^II(L ³ )Cl]Cl, where M is Ru (8) and Os (10), and [(η⁶-p-cymene)M^II(L ⁴ )Cl]Cl, where M is Ru (9) and Os (11), is reported. The compounds have been comprehensively characterized by elemental analysis, electrospray ionization mass spectrometry, spectroscopy (IR, UV–vis, and NMR), and X-ray crystallography (L ¹ ·HCl, 4·H₂O, 5, and 9·2.5H₂O). Structure–activity relationships with regard to cytotoxicity and cell cycle effects in human cancer cells as well as cyclin-dependent kinase (cdk) inhibition and DNA intercalation in cell-free settings have been established. The metal-free indolo[3,2-c]quinolines inhibit cancer cell growth in vitro, with IC₅₀ values in the high nanomolar range, whereas those of the related indolo[3,2-d]benzazepines are in the low micromolar range. In cell-free experiments, these classes of compounds inhibit the activity of cdk2/cyclin E, but the much higher cytotoxicity and stronger cell cycle effects of indoloquinolines L ¹ and 7 are not paralleled by a substantially higher kinase inhibition compared with indolobenzazepines L ⁴ and 11, arguing for additional targets and molecular effects, such as intercalation into DNA.     

Sawhorse-type diruthenium tetracarbonyl complexes containing porphyrin-derived ligands as highly selective photosensitizers for female reproductive cancer cells

Diruthenium tetracarbonyl complexes of the type [Ru₂(CO)₄(μ₂-η²-O₂CR)₂L₂] containing a Ru–Ru backbone with four equatorial carbonyl ligands, two carboxylato bridges, and two axial two-electron ligands in a sawhorse-like geometry have been synthesized with porphyrin-derived substituents in the axial ligands [1: R is CH₃, L is 5-(4-pyridyl)-10,15,20-triphenyl-21,23H-porphyrin], in the bridging carboxylato ligands [2: RCO₂H is 5-(4-carboxyphenyl)-10,15,20-triphenyl-21,23H-porphyrin, L is PPh₃; 3: RCO₂H is 5-(4-carboxyphenyl)-10,15,20-triphenyl-21,23H-porphyrin, L is 1,3,5-triaza-7-phosphatricyclo[3.3.1.1]decane], or in both positions [4: RCO₂H is 5-(4-carboxyphenyl)-10,15,20-triphenyl-21,23H-porphyrin, L is 5-(4-pyridyl)-10,15,20-triphenyl-21,23H-porphyrin]. Compounds 1–3 were assessed on different types of human cancer cells and normal cells. Their uptake by cells was quantified by fluorescence and checked by fluorescence microscopy. These compounds were taken up by human HeLa cervix and A2780 and Ovcar ovarian carcinoma cells but not by normal cells and other cancer cell lines (A549 pulmonary, Me300 melanoma, PC3 and LnCap prostate, KB head and neck, MDAMB231 and MCF7 breast, or HT29 colon cancer cells). The compounds demonstrated no cytotoxicity in the absence of laser irradiation but exhibited good phototoxicities in HeLa and A2780 cells when exposed to laser light at 652 nm, displaying an LD₅₀ between 1.5 and 6.5 J/cm² in these two cell lines and more than 15 J/cm² for the others. Thus, these types of porphyric compound present specificity for cancer cell lines of the female reproductive system and not for normal cells; thus being promising new organometallic photosensitizers.     

Syntheses, crystal structures, and magnetic properties of two cyclic dimer M2L2 complexes constructed from a new nitronyl nitroxide ligand and M(hfac)2 (M = Cu, Mn)

Two new binuclear radical complexes derived from a new long nitronyl nitroxide ligand, 2-[4-(5-pyrimidyl)phenyl]-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (4-NITPhPyrim), and M(hfac)₂ (M²⁺ = Cu²⁺, Mn²⁺; hfac⁻ = hexafluoroacetylacetonato), [Cu(hfac)₂(4-NITPhPyrim)]₂ · 4H₂O (1) and [Mn(hfac)₂(4-NITPhPyrim)]₂ · 4H₂O (2), were synthesized as well as characterized structurally and magnetically. X-ray analysis indicates that 1 and 2 are rectangle-like centrosymmetric dimer M₂L₂ complexes. Magnetic measurements indicate that there are two types of magnetic exchanges in 1: the ferromagnetic (FM) exchange between the Cu(II) ion and the directly bonded nitroxide unit (J₁ = 24.20 cm⁻¹) and the weak FM exchange of Cu-NIT through the pyrimidine and phenyl rings (J₂ = 0.62 cm⁻¹). Besides the strong antiferromagnetic (AFM) coupling between the Mn(II) ion and the directly bonded nitroxide unit (J = −87.61 cm⁻¹), there is a weak FM interaction between the two Mn-NIT pairs (θ = 0.39 K) in 2.     

Design,synthesis and evaluation of some 1,3,5-triazinyl urea and thiourea derivatives as antimicrobial agents

In an effort to establish new candidates with improved antimicrobial activities we report here the synthesis and in vitro biological evaluation of various series of compounds (5a-j) and (7a-j) which were evaluated against two Gram positive (S. aureus, B. subtilis), two Gram negative (S. typhosa, E. coli) strains and a yeast-like fungi (C. albicans) using the micro-dilution procedure. Among the synthesized compounds 2-(cyclohexyl amino)-4-(3,4-dimethoxy phenyl ethyl thioureido)-6-(2-chloro phenyl ureido) s-triazine (7e) and 2-(cyclohexyl amino)-4-(3,4-dimethoxy phenyl ethyl thioureido)-6-(4-chloro phenyl ureido) s-triazine (7g) proved to be effective with MIC (0.019 mg ML^?1) against S. typhosa & E. coli respectively.