Gold(I) metallocyclophosphazenes with antibacterial potency and antitumor efficacy. Synergistic antibacterial action of a heterometallic gold and silver-cyclophosphazene.

One of the most important uses of phosphazenes today involves its biomedical applications. They can also be employed as scaffolds for the design and construction of a variety of ligands in order to coordinate them to metallic drugs. The coordination chemistry of the (amino)cyclotriphosphazene ligand, [N3P3(NHCy)6], towards gold(I) complexes has been studied. Neutral complexes, [N3P3(NHCy)6{AuX}n] (X = Cl or C6F5; n = 1 or 2) (1-4), cationic complexes, [N3P3(NHCy)6{Au(PR3)}n](NO3)n (PR3 = PPh3, PPh2Me, TPA; n = 1, 2 or 3) (6-12) [TPA = 1,3,5-triaza-7-phosphaadamantane] and a heterometallic compound [N3P3(NHCy)6{Au(PPh3)}2{Ag(PPh3)}](NO3)3 (13) have been obtained and characterized by various methods including single-crystal X-ray diffraction for 7, which confirms the coordination of gold atoms to the nitrogens of the phosphazene ring. Compounds 1, 4, 6-13 were screened for in vitro cytotoxic activity against two tumor human cell lines, MCF7 (breast adenocarcinoma) and HepG2 (hepatocellular carcinoma), and for antimicrobial activity against five bacterial species including Gram-positive, Gram-negative, and Mycobacteria. Both the median inhibitory concentration (IC50) and minimum inhibitory concentration (MIC) values are among the lowest found for any gold or silver derivatives against the cell lines and particularly against the Gram-positive (S. aureus) strain and the mycobacteria used in this work. Structure-activity relationships are discussed in order to determine the influence of ancillary ligands and the number and type of metal atoms (silver or gold). Compounds 4 and 8 showed not only maximal potency on human cells but also some tumour selectivity. Remarkably, compound 13, with both gold and silver atoms, showed outstanding activity against both Gram-positive and Gram-negative strains (nanomolar range), thus having a cooperative effect between gold and silver, with MIC values which are similar or lower than those of gentamicine, ciprofloxacin and rifampicine. The broad spectrum antimicrobial efficacy of all these metallophosphazenes and particularly of heterometallic compound 13 could be very useful to obtain materials for surfaces with antimicrobial properties that are increasingly in demand.

Encouraging Undergraduate Marketing Students to Reflect on Critical Thinking and the Digital Gender Divide.

In today's society where there is an abundance of accessible, complex, and often false information, critical thinking (CT) is an essential skill so that citizens in general and students in particular can make complex decisions based on scientific evidence, rather than on prejudices, biases, and pre-established beliefs. In this context, the purpose of this study is to discover whether Active Learning (AL) methodology, using different technologies, contributes to improving the CT of the student body, applying it to the Digital Gender Divide (DGD). Three questionnaires were used to collect information, using both a quantitative and a qualitative approach. Open-ended questions are included for fuller answers, which are complemented by content analysis of the recordings and virtual presentations made. The results show that the AL methodology favours the development of CT in the DGD in a remarkable way. Likewise, the various technologies implemented in the methodology (e.g., the Google Applications Site, online round table discussions, role-plays, virtual presentations, and forms) are relevant to improving CT in DGD. It concludes by recommending the implementation of AL with CT as in the one carried out, to help prepare better professionals and raise awareness of how to reduce the DGD.

(Amino)cyclophosphazenes as Multisite Ligands for the Synthesis of Antitumoral and Antibacterial Silver(I) Complexes.

The reactivity of the multisite (amino)cyclotriphosphazene ligands, [N3P3(NHCy)6] and [N3P3(NHCy)3(NMe2)3], has been explored in order to obtain silver(I) metallophosphazene complexes. Two series of cationic silver(I) metallophosphazenes were obtained and characterized: [N3P3(NHCy)6{AgL}n](TfO)n [n = 2, L = PPh3 (2), PPh2Me (4); n = 3, L = PPh3 (3), PPh2Me (5), TPA (TPA = 1,3,5-triaza-7-phosphaadamantane, 6)] and nongem-trans-[N3P3(NHCy)3(NMe2)3{AgL}n](TfO)n [n = 2, L = PPh3 (7), PPh2Me (9); n = 3, L = PPh3 (8), PPh2Me (10)]. 5, 7, and 9 have also been characterized by single-crystal X-ray diffraction, thereby allowing key bonding information to be obtained. Compounds 2-6, 9, and 10 were screened for in vitro cytotoxic activity against two tumor human cell lines, MCF7 (breast adenocarcinoma) and HepG2 (hepatocellular carcinoma), and for antimicrobial activity against five bacterial species including Gram-positive, Gram-negative, and Mycobacteria strains. Both the IC50 and MIC values revealed excellent biological activity for these metal complexes, compared with their precursors and cisplatin and also AgNO3 and silver sulfadiazine, respectively. Both IC50 and MIC values are among the lowest values found for any silver derivatives against the cell lines and bacterial strains used in this work. The structure-activity relationships were clear. The most cytotoxic and antimicrobial derivatives were those with the triphenylphosphane and [N3P3(NHCy)6] ligands. A significant improvement in the activity was also observed upon a rise in the number of silver atoms linked to the phosphazene ring.

Cervix assessment for the management of labor induction: reliability of cervical length and Bishop score determined by residents.

AIM: To evaluate the reliability of two techniques of cervical ripeness assessment at the beginning of labor induction, as assessed by inexperienced observers. METHODS: A total of 120 women were prospectively studied at admission for labor induction. Two independent physicians examined consenting women successively but separately. One experienced consultant and one of the six first-year obstetrics residents composed the pairs of observers. The trainees had very limited prior experience with cervical ultrasound scan or evaluating Bishop score. Cervical length and Bishop score were evaluated according to standard methodology. Reliability was described by intraclass correlation coefficients (ICC) and coefficients of variation (COV). Ultrasound cervical length was plotted according to the Bland-Altman method. RESULTS: The median Bishop score and mean cervical length were similar for all observers. Ultrasound cervical length and Bishop score were highly reliable when evaluated by first-year residents. Ultrasound cervical length showed the highest interobserver agreement, with ICC values over 0.9 and COV values of approximately 10% or less for all trainees. The Bishop score was also reliable, but with lower ICC and higher COV values. CONCLUSION: Bishop score and ultrasound cervical length examination for the management of labor induction are accurate and easy to learn by inexperienced first-year residents. However, cervical length showed higher reliability than the Bishop score.

Luminescent iminophosphorane gold, palladium and platinum complexes as potential anticancer agents.

A series of coordination gold(III), palladium(II), and platinum(II) complexes with a luminescent iminophosphorane ligand derived from 8-aminoquinoline [Ph3P=N-C9H6N] (1), have been synthesized and structurally characterized. The coordination palladium(II) and platinum(II) compounds can evolve further, under appropriate conditions, to give stable cyclometalated endo species [M{κ3-C,N,N-C6H4(PPh2=N-8-C9H6N}Cl] (M = Pd, Pt) by C-H activation of the phenyl group of the PPh 3 fragment. Iminophosphorane 1 and the new metallic complexes are luminescent in DMSO or DMSO:H2O (1:1 mixture) solutions at RT. The compounds have been evaluated for their antiproliferative properties in a human ovarian cancer cell line (A2780S), in human lung cancer cells (A-549) and in a non-tumorigenic human embryonic kidney cell line (HEK-293T). Most compounds have been more toxic to the ovarian cancer cell line than to the non-tumorigenic cell line. The new complexes interact with human serum albumin (HSA) faster than cisplatin. Studies of the interactions of the compounds with DNA indicate that, in some cases, they exert anticancer effects in vitro based on different mechanisms of action with respect to cisplatin.

New liquid crystalline materials based on two generations of dendronised cyclophosphazenes.

A divergent approach was used for the synthesis of dendritic structures based on a cyclotriphosphazene core with 12 or 24 hydroxyl groups, by starting from [N(3)P(3)(OC(6)H(4)OH-4)(6)] and using an acetal-protected 2,2-di(hydroxymethyl)propionic anhydride as the acylating agent. Hydroxyl groups in these first- and second-generation dendrimers, G1-(OH)(12) or G2-(OH)(24), were then condensed in turn with mono- or polycatenar pro-mesogenic acids to study their ability to promote self-assembly into liquid crystalline structures. Reactions were monitored by using (31)P{(1)H} and (1)H NMR spectroscopy and the chemical structure of the resulting materials was confirmed by using different spectroscopic techniques and mass spectrometry (MALDI-TOF MS). The results were in accordance with monodisperse, fully functionalised cyclotriphosphazene dendrimers. Thermal and liquid crystalline properties were studied by using optical microscopy, differential scanning calorimetry and X-ray diffraction. The dendrimer with 12 4-pentylbiphenyl mesogenic units gives rise to columnar rectangular organisation, whereas the one with 24 pentylbiphenyl units does not exhibit mesomorphic behaviour. In the case of materials that contain polycatenar pro-mesogenic units with two aromatic rings (A4 vs. A5), the incorporation of a short flexible spacer connected to the periphery of the dendron (acid A5) was needed to achieve mesomorphic organisation. In this case, both dendrimer generations G1 A5 and G2 A5 exhibit a hexagonal columnar mesophase.