Synthesis of novel lanthanide acylpyrazolonato ligands with long aliphatic chains and immobilization of the Tb complex on the surface of silica pre-modified via hydrophobic interactions.

Five new complexes Ln(Q(C17))3(H2O)(Solv) (Ln = Y, Solv = H2O, Ln = Tb, Dy, Sm or Eu, Solv = EtOH) were synthesized with the acylpyrazolonato ligand Q(C17) bearing a long aliphatic C17H35 chain in the acyl moiety, and the crystal structure of Y(Q(C17))3(H2O)2 shows the three aliphatic chains from the coordinated ligands positioned in the same direction, affording plane layers built by Y(Q(C17))3(H2O)2 molecules connected through H-bonding interactions. The layers are stitched to each other like in "hook & loop" tapes. Luminescence of complexes was determined and the complex Tb(Q(C17))3(H2O)(EtOH) was immobilized on the surface of silica preprocessed using a C17H35CONH(CH2)3Si(OEt)3 reagent via hydrophobic interactions of long aliphatic chains. Luminescent properties and micromorphology of the obtained hybrid particles and hybrid films were investigated. Intensive green emission of the complex retains after grafting onto the silica surface. Inclusion of the complex on the surface of silica materials occurs as separate molecules, after the disruption of the H-bonding network present in the crystalline phase of the pure terbium sample.

Evaluation of (arene)Ru(II) complexes of curcumin as inhibitors of dipeptidyl peptidase IV.

Curcumin, the main component of Curcuma longa, shows an anti-hyperglycemic effect and improved insulin sensitivity. This action may be attributed at least in part to its anti-inflammatory properties and also to its possible interaction with dipeptidyl peptidase-4 (DPPIV), the enzyme that the conversion of glucagon-like peptide-1 (GLP-1), responsible for glucose tolerance into inactive GLP-1. In this work we evaluated the inhibitory activities of a series of different arene-Ru(II)-curcumin complexes on bovine kidney dipeptidyl peptidase-4 (DPPIV). We studied also the interaction of these inhibitors on the enzyme with fluorescence studies displaying the binding poses with molecular docking studies. Specifically organometallic ruthenium(II) complexes of general formula [(η(6)-arene)Ru(curcuminato)Cl], with arene being p-(i)PrC6H4Me (1), C6H6 (2), and C6Me6 (3), were evaluated for their inhibition activity toward the mammalian enzyme. Among them, 2 suppressed DPPIV activities more potently (Ki = 20.2(±0.8) µM) than 1, 3, or free curcumin, and all complexes showed an antioxidant activity as free curcumin. As shown from our docking simulations a putative binding site of the compound 2 was found on subdomains S1 and S2 of DPP-IV, where S1 hydrophobic pocket includes catalytic residues and is the primary determinant of substrate specificity for the enzyme. Collectively, our results demonstrate that the complexation of curcumin with ruthenium(II) could be a promising starting point for the development of curcumin-based DPPIV inhibitors.

Synthesis, characterization, crystal structure and preliminary reactivity behaviour of new heteropolytopic ligands based on the 1,3,5-triazine spacer and pyrazolyl, tris-pyrazolylmethyl and tris-pyrazolylethoxy bonding fragments.

Four new potentially polytopic nitrogen donor ligands based on the 1,3,5-triazine fragment, L(1)-L(4) (L(1) = 2-chloro-4,6-di(1H-pyrazol-1-yl)-1,3,5-triazine, L(2) = N,N'-bis(4,6-di(1H-pyrazol-1-yl)-1,3,5-triazin-2-yl)ethane-1,2-diamine, L(3) = 2,4,6-tris(tri(1H-pyrazol-1-yl)methyl)-1,3,5-triazine, and L(4) = 2,4,6-tris(2,2,2-tri(1H-pyrazol-1-yl)ethoxy)-1,3,5-triazine) have been synthesized and characterized. The X-ray crystal structure of L(3) confirms that its molecular nature consists of a 1,3,5-triazine ring bearing three tripodal tris(pyrazolyl) arms. L(1), L(2), and L(4) react with Cu(I), Cu(II), Pd(II) and Ag(I) salts yielding mono-, di-, and oligonuclear derivatives: [Cu(L(1))(Cy(3)P)]ClO(4), [{Ag(2)(L(2))}(CF(3)SO(3))(2)]·H(2)O, [Cu(2)(L(2))(NO(3))(2)](NO(3))(2)·H(2)O, [Cu(2)(L(2))(CH(3)COO)(2)](CH(3)COO)(2)·3H(2)O, [Pd(2)(L(2))(Cl)(4)]·2H(2)O, [Ru(L(2))(Cl)(OH)]·CH(3)OH, [Ag(3)(L(4))(2)](CF(3)SO(3))(3) and [Ag(3)(L(4))(2)](BF(4))(3). The interaction of L(3) with Ag(I), Cu(II), Zn(II) and Ru(II) complexes unexpectedly produced the hydrolysis of the ligand with formation, in all cases, of tris(pyrazolyl)methane (TPM) derivatives. In detail, the already known [Ag(TPM)(2)](CF(3)SO(3)) and [Cu(TPM)(2)](NO(3))(2), as well as the new [Zn(TPM)(2)](CF(3)SO(3))(2) and [Ru(TMP)(p-cymene)]Cl(OH)·2H(2)O complexes have been isolated. Single-crystal XRD determinations on the latter derivatives confirm their formulation, evidencing, for the Ru(II) complex, an interesting supramolecular arrangement of the anions and crystallization water molecules.

"Your ears become your eyes": managing the absence of visibility in NHS Direct.

AIMS: To identify and describe nurses' perceptions of interactional practices they use to manage the absence of visual cues in telephone consultations with callers at an NHS Direct site. BACKGROUND: A routine activity in telephone consultations is visualizing the patient and the situation from which the call is made, that is, "building a picture of the patient". Little is known about interactional practices between nurse and caller that contribute to shaping a conception of the caller, or other activities that nurses do to manage the absence of visibility in the consultation. METHODS: Qualitative analysis of semi-structured interviews conducted with nurses new to NHS Direct telephone consultations, the first immediately prior to the NHS Direct site's opening, and the second 6 months later. FINDINGS: The activity of visualizing patients and their environment is closely linked to interactional practices carried out between nurse and caller. Nurses described a range of interactional activities that they perceive help callers to describe with more precision what the nurse cannot see. Nurses also tailor interaction to a nonvisual environment in order to manage the more emotional aspects of telephone consultations, such as delivering information, advice, reassurance, and building trust and rapport. CONCLUSION: Nurses developed skills to manage interaction with callers in order to compensate for the absence of visibility. Skills were based on their professional backgrounds and experience and developed in an ad hoc way. Further research could examine the efficacy of these strategies, and be a prerequisite to adding them to training programmes.

GPs' views of discussions of prognosis in severe COPD.

BACKGROUND: Modern palliative care promotes open communication between doctor and patient, which includes access to information about prognosis. GPs play a major role in managing chronic obstructive pulmonary disease (COPD) patients in the final stages of illness. Their views of discussions of prognosis are therefore important if the principles of palliative care are to be extended to COPD. OBJECTIVE: Our aim was to investigate the role that discussions of prognosis play in GPs' management of patients with severe COPD and the factors that influence those discussions. METHODS: We conducted a questionnaire survey of all GP principals of one inner London Health Authority (n = 389) in April 1999. Questionnaire development involved a literature review to identify issues of importance to GPs in the discussion of prognosis in COPD, and in-depth interviews with five GPs. RESULTS: Of the 214 respondents (55% response), 72.5% thought that discussions of prognosis were often necessary or essential in severe COPD. The majority (82%) felt that GPs have an important role in these discussions. However, only a minority (41%) of GPs reported often or always discussing prognosis. Half the GPs were undecided as to whether most patients with COPD wanted to know about their prognosis. Among the GPs who reported rarely or never discussing prognosis (n = 33), a majority felt ill-prepared to discuss the subject (60% reported that there was insufficient information in the primary care notes to be able to discuss prognosis, and 64% found it hard to start discussions with patients). CONCLUSION: Although the majority of GPs acknowledged a need to discuss prognosis in severe COPD, this was not reflected in their reported behaviour. It appears that the palliative care approach of open communication, whilst seen to be relevant to severe COPD, is not applied routinely in managing the disease in primary care. Uncertainty among GPs as to how patients view the discussion of prognosis and inadequate preparation may pose potential barriers.

Synthesis, structure, and antitumor activity of a novel tetranuclear titanium complex.

The coordination complex cyclo-tetrakis[bis(1-phenyl-3-methyl-4-benzoylpyrazolon-5-ato++ +)mu-o xotitanium(IV)] has been synthesized and characterized with IR and NMR spectroscopies and X-ray diffraction. The core of this species consists of an eight-membered Ti-mu-oxo ring with alternate short-long Ti-O bond lengths. Besides these two O ligands, each metal is bound octahedrally to four O atoms from two chelating 1-phenyl-3-methyl-4-benzoylpyrazolon-5-ato anions. Several sets of Ti-O bond lengths are present: the shortest are the two Ti-O(oxo) (which are cis to each other), the longest are the two Ti-O(acyl) (cis to each other), and the two Ti-O(pyrazolonato) (trans to each other) are intermediate. The beta-diketonate ligand asymmetry, a feature considered essential in other antitumor Ti compounds, induces the short-long Ti-O(oxo) sequence of bond lengths. The antitumor activity of this compound, encapsulated in a dipalmitoylphosphatidylcholine liposome, has been studied in vitro using TA-3 (mouse mammary adenocarcinoma), HEP-2 (human epithelial larynx carcinoma), and VERO (African green monkey kidney) cell lines and in vivo in CF-1 and AJ female mice ip inoculated with TA-3. In vitro cytotoxicity is greater for TA-3 than for HEP-2 and null for VERO cell lines. In vivo results show a marked increase in survival time (T/C = 293% for AJ and 208% for CF-1), whereas tumor weight decrease was observed for CF-1-treated mice. These results suggest the Ti complex-liposome system may be promising as an antitumor drug.