Conformational properties of chiral tobacco alkaloids by DFT calculations and vibrational circular dichroism: (-)-S-anabasine.

A thorough DFT and MM study of the conformational landscape, molecular and electronic structures of (-)-S-anabasine is reported aimed to reveal the mechanism controlling its conformational preference. Although the conformational flexibility and diversity of this system is quite extensive, only two structures are populated both in gas-phase and solution (CCl4 and DMSO). NBO-aided electronic structure analyses performed for the eight conformers representing minima in the potential energy surface of (-)-S-anabasine indicate that both steric and electrostatic factors are determinant in the conformational distribution of the sample in gas phase. Nonetheless, hyperconjugative effects are the key force tipping the balance in the conformational equilibrium between the two main rotamers. Increasing the polarity of the medium (using the IEF-PCM formalism) barely affect the conformational energy profile, although a slight increase in the theoretical population of those structures more affected by electrostatic interactions is predicted. The validity of the theoretical models and calculated conformers populations are endorsed by the accurate reproduction of the IR and VCD spectra (recorded in pure liquid and in CCl4 solution) of the sample (that have been firstly recorded and assigned in the present work) which are consistent with the occurrence of a 2:1 conformational ratio.

Synthesis and structural study of precursors of novel methylsilanediols by IR and Raman spectroscopies, single-crystal X-ray diffraction and DFT calculations.

On the way towards the development of a synthetic route aimed at obtaining new methylsilanediol derivatives with an aminocarbonyl group in ß to silicon (which may have a potential biological interest), we have synthesized, isolated and purified five diphenylic possible precursors, namely chloromethyl(methyl)diphenylsilane, 2-{[methyl(diphenyl)silyl]methyl}-1H-isoindole-1,3(2H)-dione, N-[(methyl(diphenyl) silanyl)-methyl]-benzamide, N-[(methyl(diphenyl)silyl)-methyl]-acetamide and N-[(methyl(diphenyl)silyl)-methyl]-formamide. The conformational landscape of the five species in this study are explored by means of DFT calculations at the B3LYP/6-311++G(∗∗) level. The theoretical molecular structures predicted are confirmed by the reproduction of their respective IR and Raman spectral profiles, that are completely assigned. Some evidence in the vibrational spectra points to the occurrence of conformational mixtures in the samples. Further, single-crystal X-ray diffraction has allowed the elucidation of the crystalline structure of 2-{[methyl(diphenyl)silyl]methyl}-1H-isoindole-1,3(2H)-dione.

Self-assembly structures of 1H-indazoles in the solution and solid phases: a vibrational (IR, FIR, Raman, and VCD) spectroscopy and computational study.

1H-indazoles are good candidates for studying the phenomena of molecular association and spontaneous resolution of chiral compounds. Thus, because the 1H-indazoles can crystallize as dimers, trimers, or catemers, depending on their structure and the phase that they are in, the difficulty in the experimental analysis of the structure of the family of 1H-indazoles becomes clear. This difficulty leads us to contemplate several questions: How can we determine the presence of different structures of a given molecular species if they change according to the phase? Could these different structures be present in the same phase simultaneously? How can they be determined? To shed light on these questions, we outline a very complete strategy by using various vibrational spectroscopic techniques that are sensitive (VCD) and insensitive (IR, FIR, and Raman) towards the chirality, together with quantum chemical calculations.

Theoretical and experimental vibrational spectrum study of 4-hydroxybenzoic acid as monomer and dimer.

Theoretical calculations on the molecular geometry and the vibrational spectrum of 4-hydroxybenzoic acid were carried out by the Density Functional Theory (DFT/B3LYP) method. In addition, IR and Raman spectra of the 4-hydroxybenzoic acid in solid phase were newly recorded using them in conjunction the experimental and theoretical data (including SQM calculations), a vibrational analysis of this molecular specie was accomplished and a reassignment of the normal modes corresponding to some spectral bands was proposed. The geometries of monomers and dimers in gas phase were optimized using the DFT B3LYP method with the 6-31G*, D95** and 6-311++G** basis sets. Also, both the vibrational spectra recorded and the results of the theoretical calculations show the presence of one stable conformer for the 4-hydroxybenzoic acid cyclic dimer. The B3LYP/6-31G* method was used to study the structure for cyclic dimer of 4-hydroxybenzoic acid and for a complete assignment our results were compared with results of the cyclic dimer of benzoic acid. A scaled quantum mechanical analysis was carried out to yield the best set of harmonic force constants. The formation of the hydrogen bond was investigated in terms of the charge density by the AIM program and by the NBO calculations.

Experimental and theoretical study of the hydration of phosphate groups in esters of biological interest.

We have studied the influence of different groups esterified to phosphates on the strength of the interaction of the PO bond with one water molecule. Experimental vibrational spectra of PO(4)3-, HPO4(2-), H2PO4-, phosphoenolpiruvate (PEP) and ortho-phosphocholamine (o-PC) were obtained by means of FTIR spectroscopy. Geometry calculations were performed using standard gradient techniques and the default convergence criteria as implemented in GAUSSIAN 98 Program. In order to assess the behaviour of such DFT theoretical calculations using B3LYP with 6-31G* and 6-311++G** basis sets, we carried out a comparative work for those compounds. The results were then used to predict the principal bands of the vibrational spectra and molecular parameters (geometrical parameters, stabilisation energies, electronic density). In this work, the relative stability and the nature of the PO bond in those compounds were systematically and quantitatively investigated by means of Natural Bond Order (NBO) analysis. The topological properties of electronic charge density are analysed employing Bader's Atoms in Molecules theory (AIM). The hydrogen bonding of phosphate groups with water is highly stable and the PO bond wavenumbers are shifted to lower experimental and calculated values (with the DFT/6-311++G** basis set). Accordingly, the predicted order of the relative stability of the hydrogen bonding of the water molecule to the PO bond of the investigated compounds is: PO(4)3->HPO4(2-)>H2PO4->phosphoenolpiruvate>phosphocholamine for the two basis sets used.

[Epidemiological features of community- and nosocomial-acquired bacteremia in the hospitalized elderly patients]. / Características epidemiologías de la bacteriemia de origen comunitario y nosocomial en pacientes hospitalizados mayores de 65 años.

OBJECTIVES: To analyze the epidemiology and to identify associated factors for community- and nosocomial-acquired bacteremia in the elderly (BE). PATIENT AND METHODS: Elderly patients diagnosed of bacteremia were selected. Community- or acquired-bacteremia were defined according to standard criteria. The severity of underlying diseases was classified as non-fatal, ultimately fatal, or rapidly fatal, according to McCabe-Jackson criteria. Multivariate analysis by logistic regression was used to identify associated factors to bacteremia. RESULTS: Two hundred and forty-two cases of BE were selected. The mean age was 72.5 years, 50% occurred in males. One hundred and thirty cases (53.7%) were community-acquired and 112 (46.3%) cases were nosocomial-acquired BE. Most common underlying diseases were diabetes mellitus (30.6%%), chronic obstructive pulmonary disease (25.6%) and neoplasia (24%). Gram-negative bacteria were more frequently isolated in community-acquired BE, while gram-positive cocci were more common in nosocomial-acquired BE. Sources of infection were: vascular (19%), respiratory tract (18.6%), biliary tract (17.8%) and urinary tract (8.3%). The factors associated with nosocomial-acquired BE were (adjusted OR; 95%CI): underlying diseases (5.4; 2.7-10.8), neoplasia (2.5; 1.3-4.9) and vascular origin (2.2; 1.1-4.5). Fifty-two patients died (23.1%). CONCLUSIONS: BE occurs in elderly patients debilitated with well-defined underlying diseases. BE is associated to high mortality.

Características epidemiologías de la bacteriemia de origen comunitario y nosocomial en pacientes hospitalizados mayores de 65 años / Epidemiological features of community- and nosocomial-acquired bacteremia in the hospitalized elderly patients

Objetivos: Describir las características epidemiologías e identificar factores asociados de la bacteriemia de origen comunitario y nosocomial en el paciente anciano (BA). Pacientes y método: Se seleccionaron pacientes ancianos diagnosticados de bacteriemia significativa. La fuente de bacteriemia y la adquisición comunitaria o nosocomial fueron consideradas siguiendo definiciones estandarizadas. Según la presencia de enfermedad subyacente los pacientes fueron categorizados siguiendo los criterios de McCabe y Jackson en los siguientes grupos: rapidamente fatal, últimamente fatal, y no fatal. Se realizó análisis multivariante por regresión logística para identificar factores asociados de forma independiente a la presencia de bacteriemia. Resultados: Fueron seleccionados 242 episodios de BA, con una edad media de los pacientes de 72,5 años, siendo el 50% varones. El origen fue comunitario en 130 (53,7%) casos y nosocomial en 112 (46,3%). En el 90,9% de los casos existía alguna enfermedad subyacente, siendo las más frecuentes: diabetes mellitus (30,6%), EPOC (25,6%) y neoplasia (24%). En BA de origen comunitario los bacilos gram negativos fueron más frecuentemente aislados (60,8%) y en BA nosocomial los cocos gram positivos (58,9%). La fuente primaria de bacteriemia fue vascular (19%), respiratorio (18,6%), biliar (17,8%) y urinario (8,3%). Tras analisis multivariante el origen nosocomial de la BA se asoció a presencia de alguna enfermedad subyacente (OR: 5,4; IC95%: 2,7-10,8), neoplasia (OR: 2,5; IC95: 1,3-4,9) y fuente vascular (OR: 2,2; IC95%: 1,1-4,5). Fallecieron 56 pacientes (23,1%). Conclusiones: La BA ocurre en pacientes con enfermedades debilitantes y factores predisponentes definidos, asociandose a una alta mortalidad

Objectives: To analyze the epidemiology and to identify associated factors for community- and nosocomial-acquired bacteremia in the elderly (BE). Patient and methods: Elderly patients diagnosed of bacteremia were selected. Community- or acquired-bacteremia were definided according to standard criteria. The severity of underlying diseases was classified as non-fatal, ultimately fatal, or rapidly fatal, according to McCabe-Jackson criteria. Multivariate analysis by logistic regression was used to identify associated factors to bacteremia. Results: Two hundred and forty-two cases of BE were selected. The mean age was 72,5 years, 50% occurred in males. One hundred and thirty cases (53,7%) were community-acquired and 112 (46,3%) cases were nosocomial-acquired BE. Most common underlying diseases were diabetes mellitus (30,6%%), chronic obstructive pulmonary disease (25,6%) and neoplasia (24%). Gram-negative bacteria were more frequently isolated in community-acquired BE, while gram-positive cocci were more common in nosocomial-acquired BE. Sources of infection were: vascular (19%), respiratory tract (18,6%), biliary tract (17,8%) and urinary tract (8,3%). The factors associated with nosocomial-acquired BE were (adjusted OR; 95%CI): underlying diseases (5,4; 2,7-10,8), neoplasia (2,5; 1,3-4,9) and vascular origin (2,2; 1,1-4,5). Fifty-two patients died (23,1%). Conclusions: BE occurs in elderly patients debilitated with well-defined underlying diseases. BE is associated to high mortality

Vibrational spectra of trimethylsilanol. The problem of the assignment of the SiOH group frequencies.

The assignment of the SiOH group vibrations of trimethylsilanol, which is still controversial, is proposed. This assignment is based on theoretical B3LYP force field scaled using the constants of the (CH3)3Si group optimized to fit experimental vibrational frequencies of (CH3)3SiF and (CD3)3SiF molecules as well as the OH stretching scale factor from methanol. The ab initio force field defined in this way gives a good agreement of the theoretical vibrational frequencies of trimethylsilanol with the positions of IR and Raman bands observed in the gas phase. This force field predicts the greatest contribution of the delta SiOH coordinates to the vibration with frequency of 804 cm(-1). The elimination of the coupling of the SiOH deformation with methyl rocking modes by the normal coordinate treatment of (CD3)3SiOH gives 832 cm(-1) for silanol deformation which is in a good agreement with the 834 cm(-1) value proposed earlier for the bending mode of free silanol groups. The geometry and force field of the open chain H3SiOH trimer is computed to model the change of the delta SiOH frequencies upon formation of the hydrogen-bonded polymers. This model predicts a significant shift of SiOH bending frequencies to the 1000-1200 cm(-1) range while those of SiOD to the 800-850 cm(-1) range. These predictions allow us to ascribe the 1087 cm(-1) band observed in the IR spectrum of crystalline (CH3)3SiOH and the Raman 775 cm(-1) band of the liquid (CH3)3SiOD to deformations of the hydrogen-bonded silanol groups.

Bacteriemia neumocócica en el adulto en un hospital de tercer nivel / Pneumococcal bacteremia in the adult patient in a university hospital

Objetivos: describir la epidemiología y el espectro clínico, así como identificar factores pronósticos de la bacteriemia neumocócica (BN) en el paciente adulto. Pacientes y método: se seleccionaron pacientes mayores de 14 años diagnosticados de bacteriemia neumocócica en el periodo 1995-2000. Se recogieron datos epidemiológicos, enfermedades subyacentes, variables clínicas y evolutivas. Para identificar factores pronósticos se realizó análisis multivariante por regresión logística. Resultados: Se incluyeron 123 casos de BN, con una edad media de 56,2ñ18,3 años, siendo el 71,5 por ciento varones. La incidencia anual media de BN fue de 5,5 casos/100.000 habitantes. Los factores predisponentes más frecuentes fueron EPOC (26 por ciento), etilismo (21,1 por ciento), cirrosis hepática (21,1 por ciento), infección por VIH (19,5 por ciento) y neoplasia (18,7 por ciento por ciento). El origen pulmonar fue la fuente de infección más frecuente (71,5 por ciento). En el 10,6 por ciento de los casos no se pudo determinar fuente de infección. La tasa de resistencia a penicilina fue del 36,6 por ciento. La mortalidad fue del 30,1 por ciento. Los factores pronósticos asociados a mortalidad de forma independiente en la BN del adulto fueron hipierazotemia, presencia de infiltrados pulmonares multilobares y shock. Conclusiones: La BN es una entidad frecuente en pacientes con enfermedades debilitantes. El origen más común es pulmonar. Se asocia a una alta mortalidad. Se identifican factores pronósticos asociados a la severidad de la infección neumocócica y a la carga de enfermedades subyacentes de pacientes (AU)

Bacteriemia neumocócica en el anciano: características clínicas y factores pronósticos / Pneumococcal bacteriemia in the elderly. Clinical features and prognostic factors

Objetivos: Analizar la epidemiología y el espectro clínico, así como identificar factores pronósticos de la bacteriemia neumocócica en el paciente anciano. Pacientes y método: De forma prospectiva, se seleccionó a pacientes ancianos diagnosticados de bacteriemia neumocócica en dos hospitales de la provincia de Málaga durante el período 1995-2001 y se compararon con un grupo control de pacientes de menos de 65 años diagnosticados consecutivamente de bacteriemia neumocócica. Para identificar factores pronósticos se realizó un análisis multivariante por regresión logística. Resultados: Se seleccionaron 72 casos de bacteriemia neumocócica en ancianos, con una edad media (desviación estándar) de 73,4 (6,9) años, el 61,1 por ciento varones. La incidencia anual media de bacteriemia neumocócica en los ancianos fue de 15,1 casos/100.000 habitantes. Ningún paciente había recibido previamente vacunación neumocócica. Los factores predisponentes más frecuentes fueron: enfermedad pulmonar obstructiva crónica (40,3 por ciento) y diabetes mellitus (25 por ciento). El origen pulmonar fue la fuente de infección más frecuente en los ancianos (el 81,9 por ciento frente al 65,3 por ciento; p < 0,05; odds ratio [OR]: 2,5; intervalo de confianza [IC]: 1,1-5,6). En el 13,9 por ciento de los casos no se pudo determinar la fuente de infección. La tasa de resistencia a penicilina fue del 23,6 por ciento. La mortalidad fue superior entre los ancianos (el 34,7 frente al 18,1 por ciento; p < 0,05; OR: 2,4; IC: 1,1-5,7 por ciento). Los factores pronósticos asociados con mortalidad de forma independiente en la bacteriemia neumocócica del anciano fueron hipoalbuminemia, presencia de infiltrados pulmonares multilobares y confusión, lo que generó un modelo con una especificidad del 97,9 por ciento y un valor predictivo positivo del 88,9 por ciento. Conclusiones: La bacteriemia neumocócica en el anciano es una entidad frecuente, cuyo origen más común es el pulmonar, y se asocia con una alta mortalidad. Se describe un modelo pronóstico con alto poder predictivo (AU)

Diagnostic yield of a PCR assay in focal complications of brucellosis.

In order to evaluate the diagnostic yield of a PCR assay for patients with focal complications of brucellosis, we studied by PCR and by conventional microbiological techniques 34 nonblood samples from 32 patients with different focal forms of brucellosis. The samples from patients with brucellosis were paired to an equal number of control samples from the same locations of patients whose illnesses had different etiologies. Thirty-three of the 34 nonblood samples (97%) from the brucellosis patients were positive by PCR, whereas Brucella spp. were isolated from only 29.4% of the conventional cultures. For 11.4% of the patients, the confirmatory serological tests were either negative or showed titers below the diagnostic range. Two patients (6.2%) from the control group, both with tuberculous vertebral osteomyelitis, had a positive PCR result. The brucella PCR of blood from these two patients was also positive, and the two strains of Mycobacterium tuberculosis isolated were analyzed by the brucella PCR, with no evidence of amplification. These results show that the PCR assay is far more sensitive than conventional cultures, and this, coupled with its speed and reduction in risk to laboratory workers, makes this technique a very useful tool for the diagnosis of focal complications of brucellosis.

Experimental and ab Initio Equilibrium Structure and Harmonic Force Field of 1,2,5-Oxadiazole.

The equilibrium structure of 1,2,5-oxadiazole has been calculated ab initio at the CCSD(T) level using a polarized valence quadruple zeta basis set. The harmonic force field has also been calculated at the MP2/cc-pVTZ, B3LYP/6-311++G(3df, 2pd), and B3LYP/cc-pVQZ levels. These force fields have been subsequently scaled and further refined by fitting them to the experimental values of the vibrational fundamentals of three isotopomers and the centrifugal distortion constants of the parent molecule. The specific refinement of those scaled force constants particularly sensitive to the experimental data set was decisive for obtaining a more reliable harmonic potential. The resulting force fields are presented and used, together with the ground state rotational constants, to calculate an r(z) structure. The experimental r(0), r(s), and r(m) structures have also been determined. The different results have been compared and it is concluded that the ab initio structure is a good approximation of the equilibrium structure. It is also shown that the magnetic correction is not negligible, particularly for the inertial defect. Another interesting conclusion is that the anharmonicity of the C-H stretching might be unusually small. Copyright 2001 Academic Press.

[Community-acquired bacteremic pneumonia in the elderly]. / Neumonía bacteriémica de origen comunitario en el anciano.

OBJECTIVE: To assess the risk factors associated with the development of bacteremic community-acquired pneumonia in the elderly (BCPE) and its clinical and prognostic aspects. METHODS: We studied 36 BCPE and 72 patients with community-acquired pneumonia and negative blood cultures as control group. RESULTS: The presence of the following risk factors was more common in cases than in control subjects: alcoholism, malnutrition, diabetes and chronic renal insufficiency. The multivariate analysis demonstrated that the malnutrition (OR:3.3; CI95%:1.4-7.8) and diabetes (OR:2.5; CI95%:1.1-6.7) were independent risk factors significantly related to the development of BCPE. The presence of chills, tachycardia, tachypnea, decreased level of consciousness and hypotension blood pressure were more common in case subjects. The microbial agents implicated more frequently were S. pneumoniae and gram-negative bacilli. The bilateral involvement and two or more affected lobes on chest radiograph were more common in the cases of BCPE. The mortality rate was higher in case subjects (22.2% vs. 2.8%; p = 0.001). CONCLUSIONS: We stress the relevance of the bacteremia as prognostic factor in the community-acquired pneumonia in the elderly.

Neumonía bacteriémica de origen comunitario en el anciano / Bacteremic community-acquired pneumonia in the elderly

Objetivos: Para analizar los aspectos clínicos y pronósticos y los factores asociados al desarrollo de la neumonía bacteriémica de origen comunitario en el anciano (NBA). Métodos: Estudiamos 36 casos de NBA diagnosticados en nuestro centro en un periodo de 2 años. Se incluyó 2 pacientes, por cada caso de NBA, con neumonía adquirida en la comunidad con hemocultivo repetidamente negativo. Resultados: Los factores asociados al desarrollo de bacteriemia fueron etilismo crónico, malnutrición, diabetes mellitus e insuficiencia renal crónica. Tras análisis multivariante sólo la malnutrición (OR: 3,3; IC95%: 1,4-7,8) y la diabetes mellitus (OR: 2,5; IC95%: 1,1-6,7) se mostraron como factores de riesgo independientes. Los pacientes con NBA presentaron mayor proporción de escalofríos, taquicardia, taquipnea, disminución del nivel de conciencia e hipotensión arterial. Los gérmenes más frecuentemente aislados fueron S. pneumoniae y bacilos gram negativos. La NBA se asoció con afectación radiográfica de 2 o más lóbulos pulmonares, y a la presencia de infiltrados bilaterales. La mortalidad fue mayor en los casos de NBA (22,2% vs. 2,8%; p<0,001). Conclusiones: Se destaca la importancia de la bacteriemia como factor pronóstico en la neumonía de la comunidad del anciano (AU)