Chiral transition-metal complexes as Brønsted-acid catalysts for the asymmetric Friedel-Crafts hydroxyalkylation of indoles.

The Friedel-Crafts reaction between 3,3,3-trifluoropyruvates and indoles is efficiently catalysed by the iridium complex [(η(5)-C5Me5)Ir{(R)-Prophos}(H2O)][SbF6]2 (1) with up to 84% ee. Experimental data and theoretical calculations support a mechanism involving the Brønsted-acid activation of the pyruvate carbonyl by the protons of the coordinated water molecule in 1. Water is not dissociated during the process and, therefore, the catalytic reaction occurs with no direct interaction between the substrates and the metal.

Ruthenium amino carboxylate complexes as asymmetric hydrogen transfer catalysts.

The synthesis and characterization of optically active amino carboxylate complexes of formula [(η(6)-arene)Ru(Aa)Cl] (arene = C(6)H(6), C(6)Me(6), Aa = amino carboxylate) as well as those of the related trimers [{(η(6)-arene)Ru(Aa)}(3)][BF(4)](3) are reported. Trimerization takes place with chiral self-recognition: only diastereomers equally configured at the metal, R(Ru)R(Ru)R(Ru) or S(Ru)S(Ru)S(Ru), are detected. The crystal structures of the complexes [(η(6)-C(6)H(6))Ru(Pip)Cl] and [{(η(6)-C(6)Me(6))Ru(Pro)}(3)][BF(4)](3) have been determined by X-ray diffraction methods. Both types of complexes catalyse the hydrogen transfer reaction from 2-propanol to ketones with moderate enantioselectivity (up to 68% ee). The enantiodifferentiation achieved can be accounted for by assuming that Noyori's bifunctional mechanism is operating.

Chiral pyridylamino-ruthenium(II) complexes: synthesis, structure and catalytic properties in Diels-Alder reactions.

Half-sandwich complexes [(eta(6)-arene)RuCl(pyam)][SbF(6)] (pyam = L(n) = N-(2-pyridylmethyl)-(R)-1-phenylethylamine (L(1)), N-(2-pyridylmethyl)-(R)-1-naphthylethylamine (L(2)), N-(2-quinolylmethyl)-(R)-1-naphthylethylamine (L(3)), N-(2-pyridylmethyl)-(R)-1-cyclohexylethylamine (L(4)), N-(2-pyridylmethyl)-(1R,2S,4R)-1-bornylamine (L(5))) have been synthetised and characterised. Treatment of these compounds with AgSbF(6) generates dicationic complexes [(eta(6)-arene)Ru(pyam)(H(2)O)](2+) which act as enantioselective catalysts for the Diels-Alder reactions of methacrolein and cyclopentadiene. The catalytic reactions occur quickly at room temperature with good exo : endo selectivity (from 84 : 16 to 98 : 2) and moderate enantioselectivity (up to 74% ee). The molecular structures of the chloride complexes (R(Ru),S(N),R(C))-[(eta(6)-p-MeC(6)H(4)iPr)RuClL(1)][SbF(6)], (R(Ru),S(N),S(C2))-[(eta(6)-p-MeC(6)H(4)iPr)RuClL(5)][SbF(6)], and that of the aqua complex (R(Ru),S(N),S(C2))-[(eta(6)-p-MeC(6)H(4)iPr)RuL(5)(H(2)O)][SbF(6)](2), were determined by X-ray diffractometric methods. The distinctive variations observed in the molecular structures of these complexes only concern the puckering parameters of the metallacycle and the relative disposition of substituents within this ring. A clear trend to localise the most steric demanding substituents at equatorial positions is evident from the structural study.

Half-sandwich rhodium (and iridium) complexes as enantioselective catalysts for the 1,3-dipolar cycloaddition of 3,4-dihydroisoquinoline N-oxide to methacrylonitrile.

Cationic half-sandwich complexes containing the [(eta(5)-C(5)Me(5))M(Diphos*)] moiety (M=Rh, Ir; Diphos*=chiral diphosphine ligand) catalyze the cycloaddition of the nitrone 3,4-dihydroisoquinoline N-oxide (A) to methacrylonitrile (B) with excellent regio and endo selectivity and low-to-moderate enantioselectivity. The most active and selective catalyst, (S(Rh),R(C))-[(eta(5)-C(5)Me(5))Rh{(R)-Prophos)} (NC(Me)C==CH(2))](SbF(6))(2), has been isolated and fully characterized including the determination of the molecular structure by X-ray diffraction. The R-at-metal epimers of the complexes [(eta(5)-C(5)Me(5))M{(R)-Prophos)}(NC(Me)C==CH(2))](SbF(6))(2) (M=Rh, Ir) isomerize to the corresponding S-at-metal diastereomers. The stoichiometric cycloaddition of A with B is catalyzed by diastereopure (S(M),R(C))-[(eta(5)-C(5)Me(5))M{(R)-Prophos)}(NC(Me)C==CH(2))](SbF(6))(2) with perfect regio and endo selectivity and very good (up to 95 %) ee. The catalyst can be recycled up to nine times without significant loss of either activity or selectivity.

Pentamethylcyclopentadienyl-iridium(III) complexes with pyridylamino ligands: synthesis and applications as asymmetric catalysts for Diels-Alder reactions.

Reaction of the dimer [(Cp*IrCl)2(P-Cl)2] with chiral pyridylamino ligands (pyam, L1-L5) in the presence of NaSbF6 gave complexes [Cp*IrCl(pyam)][SbF6] 1-5 as diastereomeric mixtures, which have been fully characterised, including the X-ray molecular structure determination of the complexes (S(Ir),R(N),R(C))-[Cp*IrClL1][SbF6] 1a and (R(Ir),S(N),S(C))-[Cp*IrClL5][SbF6] 5a. Treatment of these cations with AgSbF6 affords the corresponding aqua species [Cp*Ir(pyam)(H2O)][SbF6]2 6-10 which have been also fully characterised. The molecular structure of the complex (S(Ir),R(N),R(C))-[Cp*IrL,(H2O)][SbF6]2 6 has been determined by X-ray diffractometric methods. The aqua complexes [Cp*Ir(pyam)(H2O)][SbF6]2 (6, pyam = L2 (7), L3 (8)) evolve to the cyclometallated species [Cp*Ir{kappa3(N,N',C)-(R)-(C6H4)CH(CH3)NHCH2C5NH4}][SbF6] (11), [Cp*Ir{kappa3(N,N',C)-(R)-(C10H6)CH(CH3)-NHCH2C5NH4)}][SbF6] (12), and [Cp*Ir{kappa3(N,N',C)-(R)-(C10H6)CH(CH3)NHCH2C9NH6)}][SbF6] (13) respectively, via intramolecular activation of an ortho C-H aryl bond. Complexes 6-10 are enantioselective catalysts for the Diels-Alder reaction between methacrolein and cyclopentadiene. Reaction occurs rapidly at room temperature with good exo : endo selectivity (from 81 : 19 to 98 : 2) and moderate enantioselectivity (up to 72%). The involved intermediate Lewis acid-dienophile compounds [Cp*Ir(pyam)(methacrolein)][SbF]2 (pyam = L4 (14), L5 (15)) have been isolated and characterised.

Enantioselective 1,3-dipolar cycloaddition of nitrones to methacrolein catalyzed by (eta5-C5Me5)M{(R)-prophos} containing complexes (M = Rh, Ir; (R)-prophos = 1,2-bis(diphenylphosphino)propane): on the origin of the enantioselectivity.

The rhodium and iridium Lewis-acid cations [(eta(5)-C(5)Me(5))M{(R)-Prophos}(H(2)O)](2+) ((R)-Prophos = 1,2-bis(diphenylphosphino)propane) efficiently catalyze the enantioselective 1,3-dipolar cycloaddition of nitrones to methacrolein. Reactions occur with perfect endo selectivity and with enantiomeric excesses up to 96%. Intermediates [(eta(5)-C(5)Me(5))M{(R)-Prophos}(methacrolein)](SbF(6))(2) (M = Rh (3), Ir (4)) have been spectroscopically and crystallographically characterized. The nitrone complexes [(eta(5)-C(5)Me(5))M{(R)-Prophos}(nitrone)](SbF(6))(2) (M = Rh, nitrone = 1-pyrrolidine N-oxide (5), 2,3,4,5,-tetrahydropyridine N-oxide (6), 3,4-dihydroisoquinoline N-oxide (7); M = Ir, nitrone = 1-pyrrolidine N-oxide (8)) have been isolated and characterized including the X-ray crystal structure of compounds 6 and 8. The equilibrium between methacrolein and nitrone complexes is also studied. [Ir]-adduct complexes are detected by (31)P NMR spectroscopy. A catalytic cycle involving [M]-methacrolein, [M]-nitrone, as well as [M]-adduct species is proposed, the first complex being the true catalyst. The absolute configuration of the adduct 4-methyl-2-N,3-diphenyl-isoxazolidine-4-carbaldehyde (9) was determined through its (S)-(-)-alpha-methylbenzylamine derivative diastereomer. Structural parameters strongly suggest that the disposition of the methacrolein in 3 and 4 is fixed by CH/pi attractive interactions between the pro-S phenyl ring of the Ph(2)PCH(CH(3)) moiety of the (R)-Prophos ligand and the CHO aldehyde proton. Proton NMR data indicate that this conformation is maintained in solution. From the structural data and the results of catalysis the origin of the enantioselectivity is discussed.

[Incidence of febrile episodes in patients with multiple myeloma undergoing autologous peripheral blood stem cell transplantation]. / Incidencia de episodios febriles en pacientes con mieloma múltiple sometidos a trasplante autólogo de progenitores hematopoyéticos de sangre periférica (TASPE).

BACKGROUND: Autologous peripheral blood stem cell transplantation (PBSCT) is a procedure frequently used as therapy for hematological malignancies, in which infectious complications are a major cause of morbimortality. The duration and intensity of neutropenia, indwelling central venous catheters, and mucosa chemotherapy-induced damage, contribute to increase infection rates. We have retrospectively review the incidence of febrile episodes and microbiological documented infections (MDI) in patients with multiple myeloma (MM) undergoing PBSCT. PATIENTS AND METHODS: We have retrospectively analyzed 56 PBSCT in patients diagnosed of MM between 1995 and 2002 in our hospital. RESULTS: 34 patients showed fever: 19 fever of unknown origin; 5 clinically documented infections and 10 patients MDI. We isolated 5 pathogens gram negative and 4 gram positive. We observed 2 infections associated to indwelling central venous catheters and 1 MDI due to simplex Herpes Virus. Two patients died due to infectious complications. CONCLUSIONS: The incidence of febrile episodes in our patients is similar to those previously reported as well, duration of neutropenia associated to PBSCT. We have observed a slightly higher incidence of gram negative pathogens.

Incidencia de episodios febriles en pacientes con mieloma múltiple sometidos a trasplante autólogo de progenitores hematopoyéticos de sangre periférica (TASPE) / Incidence of febrile episodes in patients with multiple myeloma undergoing autologous peripheral blood stemm cell transplantation

Introducción: El trasplante autólogo de progenitores hematopoyéticos de sangre periférica (TASPE), es un procedimiento frecuentemente empleado en el tratamiento de las hemopatías malignas, siendo la morbimortalidad atribuible a las infecciones un factor determinante en el resultado final del mismo. La duración e intensidad de la neutropenia, la presencia de catéteres venosos centrales y la alteración de las mucosas contribuyen a una mayor incidencia de infecciones. Revisamos de manera retrospectiva la incidencia de episodios febriles y en especial de infecciones microbiológicamente documentadas (IMD) en pacientes afectos de mieloma múltiple (MM) sometidos a TASPE. Pacientes y métodos: Análisis retrospectivo de una serie de 56 pacientes con MM sometidos a TASPE en nuestro hospital entre 1995 y 2002. Resultados: Treinta y cuatro pacientes presentaron fiebre: 19 episodios febriles sin foco; 5 episodios febriles clínicamente documentados y 10 pacientes IMD. Se aislaron 5 microorganismos gram negativos frente a 4 gram positivos. Se evidenció infección de catéter en 2 casos. Sólo observamos una IMD de etiología vírica por virus Herpes simple (VHS). Dos pacientes fallecieron como consecuencia del proceso infeccioso. Conclusiones: El porcentaje de procesos febriles en nuestra serie es similar al descrito en la literatura, así como la duración de la neutropenia asociada al TASPE. Observamos un discreto predominio de la infecciones por gram negativos

Background: Autologous peripheral blood stem cell transplantation (PBSCT) is a procedure frequently used as therapy for hematological malignancies, in wich infectious complications are a major cause of morbimortality. The duration and intensity of neutropenia, indwelling central venous catheters, and mucosa chemotherapy-induced damage, contribute to increase infection rates. We have retrospectively review the incidence of febrile episodes and microbiological documented infections (MDI) in patients with multiple myeloma (MM) undergoing PBSCT. Patients and methods: We have retrospectively analized 56 PBSCT in patients diagnosed of MM between 1995 and 2002 in our hospital. Results: 34 patients showed fever: 19 fever of unknown origin; 5 clinically documented infections and 10 patients MDI. We isolated 5 pathogens gram negative and 4 gram positive. We observed 2 infections associated to indwelling central venous catheters and 1 MDI due to simplex Herpes Virus. Two patiens died due to infectious complications. Conclusions: The incidence of febrile episodes in our patients is similar to those previously reported as well, duration of neutropenia associated to PBSCT. We have observed a slightly higher incidence of gram negative pathogens

The complete characterization of a rhodium Lewis acid-dipolarophile complex as an intermediate for the enantioselective catalytic 1,3-dipolar cycloaddition of C,N-diphenylnitrone to methacrolein.

The 1,3-dipolar cycloaddition reaction of C,N-diphenylnitrone with methacrolein is efficiently catalyzed by the rhodium diphosphine compound (SRh,RC)-[(eta5-C5Me5)Rh(R-Prophos)(H2O)](SbF6)2 [R-Prophos = (R)-(+)-1,2-bis(diphenylphosphino)-propane, 1.SbF6]; the asymmetric catalytic process occurs with reversal of regioselectivity, perfect endo selectivity, and up to 92% ee. The complete (NMR and X-ray analysis) characterization of the involved intermediate (SRh,RC)-[(eta5-C5Me5)Rh(R-Prophos)(methacrolein)](SbF6)2 (7.SbF6) allows us to interpret the observed selectivity.

Frozen cancellous bone allografts: positive cultures of implanted grafts in posterior fusions of the spine.

We have carried out a study on the behaviour pattern of implanted allografts initially stored in perfect conditions (aseptically processed, culture-negative and stored at -80 degrees C) but which presented positive cultures at the implantation stage. There is no information available on how to deal with this type of situation, so our aim was to set guidelines on the course of action which would be required in such a case. This was a retrospective study of 112 patients who underwent a spinal arthrodesis and in whom a total of 189 allograft pieces were used. All previous bone and blood cultures and tests for hepatitis B and C, syphilis and HIV (via PCR techniques) were negative. The allografts were stored by freezing them at -80 degrees C. A sample of the allograft was taken for culture in the operating theatre just before its implantation in all cases. The results of the cultures were obtained 3-5 days after the operation. There were 22 allografts with positive culture results (12%) after implantation. These allografts were implanted in 16 patients (14%). Cultures were positive for staphylococci coagulase negative (ECN) in 10 grafts (46%), Pseudomonas stutzeri in two grafts (9%), Corynebacterium jeikeium in two grafts (9%), staphylococci coagulase positive in two grafts (9%) and for each of the following organisms in one case each (4%): Corynebacterium spp., Actinomyces odontolyticus, Streptococcus mitis, Peptostreptococcus spp., Rhodococcus equi and Bacillus spp. No clinical infection was seen in any of these patients. Positive cultures could be caused by non-detected contamination at harvesting, storing or during manipulation before implantation. The lack of clinical signs of infection during the follow-up of our patients may indicate that no specific treatment different from our antibiotic protocol is required in the case of positive culture results of a graft piece after implantation.

Sellado antibiótico de catéteres intravasculares centrales. Presentación de un caso tipo y de un protocolo de sellado antibiótico / No disponible

El uso de catéteres intravasculares tunelizados centrales supone una aportación fundamental a la medicina moderna. La infección asociada a estos dispositivos es una de las causas más frecuentes de infección nosocomial en nuestro medio. La simple retirada de un catéter infectado puede ser suficiente para el control de la infección, sin embargo, en muchos casos esta retirada es problemática. En este trabajo se presenta un protocolo de sellado antibiótico aplicable a pacientes diagnosticados de infección asociada a catéter (AU)

Use of central intravascular catheters is a common practice in our hospital. Catheter related infection is a major cause of nosocomial infection. Withdrawal can be enough to manage these infections, but this is not always possible. In this article we present an antibiotic lock therapy protocol that can be used in catheter related infection (AU)

The enterococcal surface protein, Esp, is involved in Enterococcus faecalis biofilm formation.

The enterococcal surface protein, Esp, is a high-molecular-weight surface protein of unknown function whose frequency is significantly increased among infection-derived Enterococcus faecalis isolates. In this work, a global structural similarity was found between Bap, a biofilm-associated protein of Staphylococcus aureus, and Esp. Analysis of the relationship between the presence of the Esp-encoding gene (esp) and the biofilm formation capacity in E. faecalis demonstrated that the presence of the esp gene is highly associated (P < 0.0001) with the capacity of E. faecalis to form a biofilm on a polystyrene surface, since 93.5% of the E. faecalis esp-positive isolates were capable of forming a biofilm. Moreover, none of the E. faecalis esp-deficient isolates were biofilm producers. Depending on the E. faecalis isolate, insertional mutagenesis of esp caused either a complete loss of the biofilm formation phenotype or no apparent phenotypic defect. Complementation studies revealed that Esp expression in an E. faecalis esp-deficient strain promoted primary attachment and biofilm formation on polystyrene and polyvinyl chloride plastic from urine collection bags. Together, these results demonstrate that (i) biofilm formation capacity is widespread among clinical E. faecalis isolates, (ii) the biofilm formation capacity is restricted to the E. faecalis strains harboring esp, and (iii) Esp promotes primary attachment and biofilm formation of E. faecalis on abiotic surfaces.

Estudio de la infección asociada a catéter intravascular durante el año 1998 en la Clínica Universitaria de Navarra / Intravascular catheter related infections during the year 1998 in the University Clinic of Navarra

Objetivos: Estudio de la infección y bacteriemia asociada a catéter intravascular (CIV) desde enero de 1998 a enero de 1999 en nuestro hospital, y de la posibilidad del empleo de una metodología diagnóstica conservadora, que no implique la retirada del CIV, de la infección asociada a catéter (IAC).Material y métodos: Se estudiaron un total de 540 puntas de CIV combinando la técnica semicuantitativa de Maki con una modificación de la técnica cuantitativa descrita por Cleri. Se clasificaron los catéteres en dos grupos, según cumpliesen criterios de infección asociada a catéter o no, y se correlacionaron con la presencia o ausencia de bacteriemia asociada. Resultados: Sólo un 24.5 por ciento de los pacientes a los que se les retiró un CIV por sospecha de infección cumplían criterios de IAC. El 44.7 por ciento de los pacientes que cumplían criterios de IAC tuvieron una bacteriemia asociada a catéter (BAC), mientras que sólo el 1.7 por ciento de los pacientes sin criterios de IAC tuvieron una bacteriemia, sin poderse filiar el origen de la misma en el CIV. Los microorganismos más frecuentemente aislados fueron los estafilococos coagulasa negativos (63 por ciento) seguidos de corinebacterias (7.7 por ciento) y Staphylococcus aureus (6.1 por ciento).Discusión y conclusiones: El 74.5 por ciento de los CIV retirados por sospecha de infección asociada en nuestro hospital hubiesen podido mantenerse, ya que éstos no cumplían criterios de IAC. Este grupo de pacientes se hubiese podido beneficiar de un diagnóstico conservador (AU)

[Infection associated with intravascular catheter in 1998 at the University Clinic of Navarra]. / Estudio de la infección asociada a catéter intravascular durante el año 1998 en la Clínica Universitaria de Navarra.

PURPOSE: To study the intravascular catheter related infections (CRI) since January of 1998 to January of 1999 in our hospital. METHODS: We studied 540 catheter tips using a modified combination of the cuantitative method of Cleri and the semicuantitative method of Maki. The catheters were classified into two groups according to the presence or absence of criteria for CRI. RESULTS: 74.5% of the retired catheters because of infection suspice did not satisfied criteria for CRI. 44.7% of the patients with criteria suffered a catheter-related bacteriemia while just 1.7% of the patients without criteria suffered a bacteriemia. The most common isolated microorganisms were coagulase-negative Staphylococci, Corynebacterium species and S. aureus. DISCUSSION AND CONCLUSIONS: At least, 74.5% of the patients with a suspice of catheter related infection could undergo a non invasive diagnosis procedure that would have showed that the catheter was not infected.

Synthesis and Characterization of Heterodinuclear IrCo, RuCo, IrNi, and RuNi Complexes Containing Pyrazolate and Pyrazolylborate Ligands.

Treatment of the metallo ligands [ML(pz)(2)(Hpz)] (pz = pyrazolate; L = C(5)Me(5), M = Ir (1); L = mesitylene, M = Ru (3)) with [M'Cl{HB(3-i-Pr-4-Br-pz)(3)}] (M' = Co (4), Ni (5)) yields heterodinuclear complexes of formula [LM(&mgr;-pz)(2)(&mgr;-Cl)M'{HB(3-i-Pr-4-Br-pz)(3)}] (L = C(5)Me(5); M = Ir; M' = Co (6), Ni (7). L = mesitylene; M = Ru; M' = Co (8)). The related complex [Ru(eta(6)-p-cymene)(pz)(2)(Hpz)] (2) reacts with equimolar amounts of 4 or 5 to give mixtures of the corresponding bis(&mgr;-pyrazolato) &mgr;-chloro complexes [(eta(6)-p-cymene)Ru(&mgr;-pz)(2)(&mgr;-Cl)M'{HB(3-i-Pr-4-Br-pz)(3)}] (M' = Co (9), Ni (10)) and the triply pyrazolato-bridged complexes [(eta(6)-p-cymene)Ru(&mgr;-pz)(3)M'{HB(3-i-Pr-4-Br-pz)(3)}] (M' = Co (11), Ni (12)). Complex 1 reacts with 5 in the presence of KOH to give the IrNi complex [(eta(5)-C(5)Me(5))Ir(&mgr;-pz)(3)Ni{HB(3-i-Pr-4-Br-pz)(3)}] (13) whereas its reaction with 4 and KOH rendered the bis(&mgr;-pyrazolato) &mgr;-hydroxo complex [(eta(5)-C(5)Me(5))Ir(&mgr;-pz)(2)(&mgr;-OH)Co{HB(3-i-Pr-4-Br-pz)(3)}] (14). The molecular structure of the heterobridged IrCo complex (6) and those of the homobridged RuNi (12) and IrNi (13) complexes have been determined by X-ray analyses. Compound 6 crystallizes in the monoclinic space group P2(1)/n, with a = 10.146(5) Å, b = 18.435(4) Å, c = 22.187(13) Å, beta = 97.28(4) degrees, and Z = 4. Complex 12 is monoclinic, space group P2(1), with a = 10.1169(7) Å, b = 21.692(2) Å, c = 11.419(1) Å, beta = 112.179(7) degrees, and Z = 2. Compound 13 crystallizes in the monoclinic space group Cc, with a = 13.695(2) Å, b = 27.929(6) Å, c = 13.329(2) Å, beta = 94.11(4) degrees, and Z = 4. All the neutral complexes 6, 12, and 13 consist of linear M.M'.B backbones with two (6) or three (12, 13) pyrazolate ligands bridging the dimetallic M.M' units and three substituted 3-i-Pr-4-Br-pz groups joining M' to the boron atoms. The presence in the proximity of the first-row metal M' of the three space-demanding isopropyl substituents of the pyrazolate groups induces a significant trigonal distortion of the octahedral symmetry, yielding clearly different M'-N bond distances on both sides of the ideal octahedral coordination sphere of these metals.