From phosphanylphosphaalkenes to coordination copper and silver polymers containing P-P bonds.

This study was focused on the activation of the CP bond via reactions of Ph2CP-PtBu2 (1) with 1,6-hexanediol and selected dithiols (1,4-butanedithiol, 1,4-benzenedithiol and 1,4-benzenedimethanethiol). These reactions proceed according to a 1,2-addition mechanism, providing new compounds with formulas {(Ph)2(H)C-P-PtBu2}{µ2-(O-(CH2)6-O)}{tBu2P-P-C(H)(Ph)2} (2), {(Ph)2(H)C-P-PtBu2}{µ2-(S-(CH2)4-S)}{tBu2P-P-C(H)(Ph)2} (3a), {(Ph)2(H)C-P-PtBu2}{µ2-(S-C6H4-S)}{tBu2P-P-C(H)(Ph)2} (3b), and {(Ph)2(H)C-P-PtBu2}{µ2-(S-CH2-C6H4-CH2-S)}{tBu2P-P-C(H)(Ph)2} (3c). Next, the reactions of 3a and 3c with metal chlorides led to the growth of desired coordination polymers of copper(I) and silver(I). All the obtained compounds remained stable under atmospheric conditions.

Understanding the Exchange Interaction between Paramagnetic Metal Ions and Radical Ligands: DFT and Ab Initio Study on Semiquinonato Cu(II) Complexes.

The exchange coupling, represented by the J parameter, is of tremendous importance in understanding the reactivity and magnetic behavior of open-shell molecular systems. In the past, it was the subject of theoretical investigations, but these studies are mostly limited to the interaction between metallic centers. The exchange coupling between paramagnetic metal ions and radical ligands has hitherto received scant attention in theoretical studies, and thus the understanding of the factors governing this interaction is lacking. In this paper, we use DFT, CASSCF, CASSCF/NEVPT2, and DDCI3 methods to provide insight into exchange interaction in semiquinonato copper(II) complexes. Our primary objective is to identify structural features that affect this magnetic interaction. We demonstrate that the magnetic character of Cu(II)-semiquinone complexes are mainly determined by the relative position of the semiquinone ligand to the Cu(II) ion. The results can support the experimental interpretation of magnetic data for similar systems and can be used for the in-silico design of magnetic complexes with radical ligands.

Activation of the C[double bond, length as m-dash]P bond in phosphanylphosphaalkenes (C[double bond, length as m-dash]P-P bond system) in the reaction with nucleophilic reagents: MeLi, nBuLi and tBuLi.

Three reactions of phosphanylphosphaalkene (1) with nucleophiles were performed to activate the diphosphorus monomer. We observed similar results in the reactions with MeLi and nBuLi, in which the P-P bond is cleavaged and triphosphorus systems [P(Me)2-CH(biph)-CH(biph)-P-(PtBu2)]- (1a'') and [P(nBu)2-CH(biph)-CH(biph)-P-(PtBu2)]- (1b''), respectively, are formed depending on the nucleophilic reagent (biph = biphenyl). In the case of tBuLi, the P-P bond remains intact; on the phosphorus atom, only one -tBu group is substituted, and as a result, [(biph)(H)C-P(tBu)-PtBu2]- (1c) is generated as a stable carbanion. We additionally investigated the effect of substitution in the phenyl ring in the course of these reactions by involving two other phosphanylphosphaalkenes (3 and 4). All initial reactions were conducted in tetrahydrofuran (THF) solution at ambient temperature.

Two out of Three Musketeers Fight against Cancer: Synthesis, Physicochemical, and Biological Properties of Phosphino CuI, RuII, IrIII Complexes.

Two novel phosphine ligands, Ph2PCH2N(CH2CH3)3 (1) and Ph2PCH2N(CH2CH2CH2CH3)2 (2), and six new metal (Cu(I), Ir(III) and Ru(II)) complexes with those ligands: iridium(III) complexes: Ir(η5-Cp*)Cl2(1) (1a), Ir(η5-Cp*)Cl2(2) (2a) (Cp*: Pentamethylcyclopentadienyl); ruthenium(II) complexes: Ru(η6-p-cymene)Cl2(1) (1b), Ru(η6-p-cymene)Cl2(2) (2b) and copper(I) complexes: [Cu(CH3CN)2(1)BF4] (1c), [Cu(CH3CN)2(2)BF4] (2c) were synthesized and characterized using elemental analysis, NMR spectroscopy, and ESI-MS spectrometry. Copper(I) complexes turned out to be highly unstable in the presence of atmospheric oxygen in contrast to ruthenium(II) and iridium(III) complexes. The studied Ru(II) and Ir(III) complexes exhibited promising cytotoxicity towards cancer cells in vitro with IC50 values significantly lower than that of the reference drug-cisplatin. Confocal microscopy analysis showed that Ru(II) and Ir(III) complexes effectively accumulate inside A549 cells with localization in cytoplasm and nuclei. A precise cytometric analysis provided clear evidence for the predominance of apoptosis in induced cell death. Furthermore, the complexes presumably induce the changes in the cell cycle leading to G2/M phase arrest in a dose-dependent manner. Gel electrophoresis experiments revealed that Ru(II) and Ir(III) inorganic compounds showed their unusual low genotoxicity towards plasmid DNA. Additionally, metal complexes were able to generate reactive oxygen species as a result of redox processes, proved by gel electrophoresis and cyclic voltamperometry. In vitro cytotoxicity assays were also carried out within multicellular tumor spheroids and efficient anticancer action on these 3D assemblies was demonstrated. It was proven that the hydrocarbon chain elongation of the phosphine ligand coordinated to the metal ions does not influence the cytotoxic effect of resulting complexes in contrast to metal ions type.

Can Dog-Assisted Intervention Decrease Anxiety Level and Autonomic Agitation in Patients with Anxiety Disorders?

Few studies have explored the influence of an Animal-Assisted Intervention on patients with mental disorders. We investigated it's impact on anxiety symptoms. We divided 51 patients with anxiety symptoms into two groups-treatment group, that went for a short 15-20 min' walk with a dog, his handler and a researcher and control group, that went for a walk only with a researcher. We used State-Trait Anxiety Inventory (STAI), Visual Analogue Scale (VAS) of fear, Beck Depression Inventory (BDI), Ford Insomnia Response to Stress (FIRST), Brief symptom Inventory (BSI) and VAS of satisfaction after trial to assess. We also checked the resting blood pressure and resting heart rate before and after performing psychological tests while sitting. We have obtained full data of 21 people from the research group and 26 people from the control group. After the intervention, the treatment group reported lower anxiety levels as a state (Mean (M) = 34.35; Standard Deviation (SD) = 6.9 vs. M = 40.94; SD = 8.6) and fear (M = 1.05; SD = 1.0 vs. M = 2.04; SD = 2.2) than the control group. After a walk with a dog, trait anxiety (M = 34.35; SD = 6.9 vs. M = 46.3; SD = 9.6), state anxiety (M = 48.9; SD = 7.2 vs. M = 53.9; SD = 7.8), fear (M = 1.05; SD= 1.0 vs. M = 2.57; SD = 2.3) and resting heart rate (M = 71.05; SD = 12.3 vs. M = 73.67; SD = 13.1) decreased significantly, while walking without a dog only reduced state anxiety (M = 47.24; SD = 11.0 vs. M = 40.94; SD = 8.6). Multivariate analysis of variance showed that after the walk, state anxiety was significantly lower in the treatment group than in the control group, F(1.35) = 6.706, p <0.05, η2 = 0.161. Among those who walked with a dog, the intervention also led to significant decreases in fear and resting heart rate, F(1.44) = 11.694, p < 0.01, η2 = 0.210 and F(1.45) = 8.503; p < 0.01; η2 = 0.159, respectively. For anxious patients, a short walk with a dog is more beneficial than a walk without one. We found significant positive effects of a dog's company on vegetative arousal and mental comfort. This is another study confirming the possible therapeutic effect of the animal on anxiety symptoms. Further research is required, especially in the large groups of patients, as recommendations on the use of Animal Assisted Interventions (AAI) are needed.

Experimental and theoretical investigation of the reactivity of [(BDI*)Ti(Cl){η2-P(SiMe3)-PiPr2}] towards selected ketones.

In this work, we report a new type of reactivity of [(BDI*)Ti(Cl){η2-P(SiMe3)-PiPr2}] (1) towards ketones (BDI* = 2,6-diisopropylphenyl-ß-methyldiketiminate ligand). In the reaction of 1 with acetone, cyclopentanone or cyclohexanone, a ketone moiety is inserted into Ti-Pphosphanyl or Ti-Pphosphido bonds to form complexes with a new C-P-P moiety, providing [(BDI*)Ti(Cl){η2-P(SiMe3)-PiPr2-C(Me)2O}] (2a), [(BDI*)Ti(Cl){η2-OC(Me)2P(SiMe3)-PiPr2}] (2b), [(BDI*)Ti(Cl){η2-P(SiMe3)-P(iPr)2-{C(CH2)4}O}] (3a), and [(BDI*)Ti(Cl){η2-P(SiMe3)-P(iPr)2-{C(CH2)5}O}] (4a). Starting complex 1 reacts with cyclohexanone, yielding a monocrystalline complex [{(ArN[double bond, length as m-dash]C(Me)CHC(Me)[double bond, length as m-dash]NAr)C(CH2)5O}Ti(Cl){PiPr2-P(SiMe3)C(CH2)5O}] (4d) with the insertion of two ketone molecules. Interestingly, we found that monoinserted complexes 2a and 3a may be oxidized via a reaction with AgCl, leading to elimination of the -SiMe3 group and oxidation of the titanium atom. This reaction led us to isolate the Ti(iv) complex [(BDI*)Ti(Cl){η2-P-P(iPr)2-{C(CH2)5}O}] (5) in crystalline form. To identify the kinds of products that may be formed and determine which products are the most energetically favoured ones, we conducted a thermodynamic DFT study of 1 towards acetone, cyclopentanone and cyclohexanone. Structures 2a, 2b, 3a, 3e, 4a, 4d, and 5 were characterized by X-ray crystallography, and complex 5 was also identified by NMR spectroscopy.

Synthesis of compounds with C-P-P and C[double bond, length as m-dash]P-P bond systems based on the phospha-Wittig reaction.

A reactivity study of a ß-diketiminate titanium(iii) phosphanylphosphido complex [MeNacNacTi(Cl){η2-P(SiMe3)-PtBu2}] (1) towards ketones such as benzophenone, 9-fluorenone, acetophenone, cyclopentanone, cyclohexanone and cycloheptanone is reported. The reactions of 1 with aromatic ketones (without α-protons) directly lead to the Ti(iii) complex [MeNacNacTi(µ2-Cl)(OSiMe3)] (5) and Ti(iv) complexes with the pinacol condensation product [MeNacNacTi(OSiMe3)(η2-pinacolate)] (3), and phosphanylphosphaalkenes Ph2C[double bond, length as m-dash]P-PtBu2 (2) and (fluorenyl)C[double bond, length as m-dash]P-PtBu2 (6), respectively. The reaction with acetophenone leads to the titanium(iii) complex with the aldol condensation product as ligand [MeNacNacTi(Cl){OC{Me(Ph)}CH2(C[double bond, length as m-dash]O)Ph}] (8) and in parallel to phosphanylphosphaalkene (Ph)MeC[double bond, length as m-dash]P-PtBu2 (9) and 5. The reactions of 1 with cyclic ketones (cyclopentanone and cyclohexanone) lead to Ti(iii) complexes [{(ArN[double bond, length as m-dash]C(Me)CHC(Me)[double bond, length as m-dash]NAr)((CH2)4CO)}Ti(Cl){PtBu2-P(SiMe3)((CH2)4CO)}] (10) and [{(ArN[double bond, length as m-dash]C(Me)CHC(Me)[double bond, length as m-dash]NAr)((CH2)5CO)}Ti(Cl){PtBu2-P(SiMe3)((CH2)5CO)}] (11), which are formed via the successive insertion of two molecules of ketone to one molecule of 1. The stability investigation of complexes 10 and 11 in a polar solvent (THF) revealed that under these conditions, the complexes decompose, resulting in titanium(iii) complexes with aldol condensation products and the expected phosphanylphosphaalkenes (CH2)4C[double bond, length as m-dash]P-PtBu2 (10a) and (CH2)5C[double bond, length as m-dash]P-PtBu2 (11a). In the reaction of 1 with cycloheptanone, only the Ti(iii) complex with the aldol condensation product [MeNacNacTi(Cl){OC(CH2)6}CH(C[double bond, length as m-dash]O)(CH2)5] (12) was isolated. The structures 3, 5, 8, 10, 11, 11b and 12 were characterized by X-ray spectroscopy, while all the phosphanylphosphaalkenes were characterized by NMR spectroscopy.

Antibacterial activity and action mode of Cu(I) and Cu(II) complexes with phosphines derived from fluoroquinolone against clinical and multidrug-resistant bacterial strains.

Biological activity against reference and multi-drug resistant (MDR) clinical strains of fluoroquinolones (FQs): ciprofloxacin (HCp), norfloxacin (HNr), lomefloxacin (HLm) and sparfloxacin (HSf), phosphine ligands derived from those antibiotics and 14 phosphino copper(I) and copper(II) complexes with 2,9-dimethyl-1,10-phenanthroline, 1,10-phenanthroline or 2,2'-biquinoline have been determined. Almost all phosphines showed excellent antibacterial activity relative to reference strains (S. aureus ATCC 6538, E. coli ATCC 25922, K. pneumoniae ATCC 4352, and P. aeruginosa ATCC 27853). In rare cases P. aeruginosa rods showed natural insensitivity to oxides, and their copper(II) complexes. Most of the studied compounds showed weak antibacterial activity against clinical multi-drug resistant strains (MDR P. aeruginosa 16, 46, 325, 355, MRD A. baumanii 483 and MDR S. aureus 177). However, phosphines Ph2PCH2Sf (PSf), Ph2PCH2Lm (PLm) and their copper(I) complexes were characterized by the best antibacterial activity. In addition, PSf compounds, in which the activities relative to P. aeruginosa MDRs were relatively diverse, paid particular attention in our studies. Genetic and phenotypic studies of these strains showed significant differences between the strains, indicating different profiles of FQs resistance mechanisms. This may prove that a change in the spatial conformation of the PSf derivatives relative to the native form of HSf increased its affinity for the target site of action in gyrase, leading to selective inhibition of the multiplication of MDR strains. In conclusion, differences in PSf activity within closely related P. aeruginosa strains may indicate its diagnostic and therapeutic potential.

Reactions of (Ph)tBuP-P(SiMe3)Li·3THF with [(PNP)TiCl2] and [MeNacNacTiCl2·THF]: synthesis of first PNP titanium(iv) complex with the phosphanylphosphinidene ligand [(PNP)Ti(Cl){η2-P-P(Ph)tBu}].

Herein, the lithium derivative of diphosphane, (Ph)tBuP-P(SiMe3)Li (1), is isolated for the first time and investigated in reactions with ß-diketiminate (MeNacnac- = [Ar]NC(Me)CHC(Me)N[Ar]; Ar = 2,6-iPr2C6H3) and PNP-pincer (PNP = N[2-PiPr2-4-methylphenyl]2) Ti(iii) complexes. The ß-diketiminate titanium(iii) complex containing the phosphanylphosphido ligand [MeNacNacTi(Cl){η2-P(SiMe3)-P(Ph)tBu}] (2) is prepared via the reaction of [MeNacNacTiCl2·THF] with (Ph)tBuP-P(SiMe3)Li in toluene solution with good yield and purity. The corresponding titanium(iv) complex involving the phosphanylphosphinidene ligand [MeNacNacTi(Cl){η2-P-P(Ph)tBu}] (3) is synthesized via the oxidation of complex (2) with [iBu3PAgCl]4. Interestingly, an analogous PNP titanium(iv) complex, [(PNP)Ti(Cl){η2-P-P(Ph)tBu}] (4), is obtained in the reaction of [(PNP)TiCl2] with (Ph)tBuP-P(SiMe3)Li in toluene solution and a 1 : 1 molar ratio instead of the expected titanium(iii) complex with the phosphanylphosphido ligand. The solid-state structures of (Ph)tBuP-P(SiMe3)Li·3THF (1), [MeNacNacTi(Cl){η2-P(SiMe3)-P(Ph)tBu}] (2), [MeNacNacTi(Cl){η2-P-P(Ph)tBu}] (3) and [(PNP)Ti(Cl){η2-P-P(Ph)tBu}] (4) are determined by single-crystal X-ray diffraction, which reveals that in all obtained complexes, both the phosphanylphosphinidene (Ph)tBuP-P and phosphanylphosphido (Ph)tBuP-P(SiMe3) ligands are bidentate-coordinated to the metal center.

Distribution of Malassezia species on the skin of patients with atopic dermatitis, psoriasis, and healthy volunteers assessed by conventional and molecular identification methods.

BACKGROUND: The Malassezia yeasts which belong to the physiological microflora of human skin have also been implicated in several dermatological disorders, including pityriasis versicolor (PV), atopic dermatitis (AD), and psoriasis (PS). The Malassezia genus has repeatedly been revised and it now accommodates 14 species, all but one being lipid-dependent species. The traditional, phenotype-based identification schemes of Malassezia species are fraught with interpretative ambiguities and inconsistencies, and are thus increasingly being supplemented or replaced by DNA typing methods. The aim of this study was to explore the species composition of Malassezia microflora on the skin of healthy volunteers and patients with AD and PS. METHODS: Species characterization was performed by conventional, culture-based methods and subsequently molecular techniques: PCR-RFLP and sequencing of the internal transcribed spacer (ITS) 1/2 regions and the D1/D2 domains of the 26S rRNA gene. The Chi-square test and Fisher's exact test were used for statistical analysis. RESULTS: Malassezia sympodialis was the predominant species, having been cultured from 29 (82.9%) skin samples collected from 17 out of 18 subjects under the study. Whereas AD patients yielded exclusively M. sympodialis isolates, M. furfur isolates were observed only in PS patients. The isolation of M. sympodialis was statistically more frequent among AD patients and healthy volunteers than among PS patients (P < 0.03). Whether this mirrors any predilection of particular Malassezia species for certain clinical conditions needs to be further evaluated. The overall concordance between phenotypic and molecular methods was quite high (65%), with the discordant results being rather due to the presence of multiple species in a single culture (co-colonization) than true misidentification. All Malassezia isolates were susceptible to cyclopiroxolamine and azole drugs, with M. furfur isolates being somewhat more drug tolerant than other Malassezia species. CONCLUSIONS: This study provides an important insight into the species composition of Malassezia microbiota in human skin. The predominance of M. sympodialis in both normal and pathologic skin, contrasts with other European countries, reporting M. globosa and M. restricta as the most frequently isolated Malassezia species.