Synthesis, structural characterization, and computational studies of novel diiodine adducts with the heterocyclic thioamides N-methylbenzothiazole-2-thione and benzimidazole-2-thione: implications with the mechanism of action of antithyroid drugs

Reaction of N-methylbenzothiazole-2-thione (C8H7NS2 or NMBZT) with diiodine produced the charge-transfer (ct) complex [(NMBZT).I2] (1). NMBZT reacts with diiodine in the presence of FeCl3 in a molar ratio of 3:6:1 and forms the ionic complex [[(NMBZT)2I+].[FeCl4]-] (2) together with [[(NMBZT)2I+].[I7]-] (2a) iodonium salt. The reaction of benzimidazole-2-thione (C7H6N2S or MBZIM) with diiodine on the other hand results in the formation of the ct [[(MBZIM)2I]+[I3]-].[(MBZIM).I2] (3) compound. The compounds have been characterized by elemental analyses, DTA-TG, FT-Raman, FT-IR, UV-vis, and 1H NMR spectroscopies, and X-ray crystal structure determinations. Compound 1, C8H7I2NS2, is orthorhombic with a space group Pna2(1) and a = 12.5147(13) angstroms, b = 22.536(3) angstroms, c = 4.2994(5) angstroms, and Z = 4. Compound 2, C16H14Cl4FeIN2S4, is monoclinic, space group C2/c, a = 35.781(2) angstroms, b = 7.4761(5) angstroms, c = 18.4677(12) angstroms, beta = 107.219(1) degrees, and Z = 8. Compound 3, C21H18I6N6S3, monoclinic, space group P2(1)/n, a = 14.0652(11) angstroms, b = 22.536(3) angstroms, c = 4.2994(5) angstroms, beta = 99.635(7) degrees, and Z = 4, consists of two component moieties cocrystallized, one neutral which contains the benzimidazole-2-thione (MBIZM) ligand bonded with an iodine atom through sulfur, forming a compound with a "spoke" structure [(MBZIM)I2] 3a, while the other is the ionic complex [[(MBZII)2I+].[I3]-] (3b). The X-ray crystal structure of 1 shows a bond between the thione-sulfur atom and one of the iodine atoms in an essentially planar arrangement. In the cation of 2, an iodine is coordinated by two thione-sulfur atoms in a linear arrangement but the molecule is not planar. For the first time in the solid state a spoke-ionic mixed complex has been characterized in 3. One component of the structure is a molecular diiodine adduct, i.e., [(MBZIM)I2] (3a), with a linear coordination geometry in a decidedly planar arrangement, and the other component is an ionic adduct [[(MBZIM)2I]+.[I3]-] (3b) with the cation having an arrangement similar to that found for 1. Theoretical calculations using density functional (DFT) and ab initio Hartree-Fock theory have been carried out for 1 and 3a,b. The results are consistent with the experimental data. Conclusions on the behavior of a thioamide, when used as an antithyroid drug, have also been made.     

3D QSAR/CoMFA and CoMSIA studies on antileukemic steroidal esters coupled with conformationally flexible nitrogen mustards

Thirty-eight antileukemic steroidal esters possessing conformationally flexible nitrogen mustards were studied, and the 3D QSAR/CoMFA and CoMSIA methodologies were applied in order to derive the correlation between their structure and the in vivo antileukemic activity. These compounds show significantly reduced toxicity and possibly increased bioavailability compared to free nitrogen mustards and therefore constitute potent antileukemic drugs. Both the CoMFA and CoMSIA studies gave similar results indicating that the steric effect and the hydrophobic/hydrophilic balance especially in the steroidal part of the molecules probably determined their bioactivity. Of paramount interest is the observation that the orientation of the alkylating part of the SMEs toward the surface of ring B of the steroidal skeleton was related with increased activity. Concerning the steroidal part, the presence of hydrophobic groups in rings B and D was found to be important for enhanced activity. Enhancement of antileukemic potency is further observed if hydrophilic/H-bond acceptor groups are present at the positions 7 and 17 of the steroidal skeleton. Leapfrog simulations provided novel compounds which lead our future synthetic endeavor for obtaining SMEs with optimum bioactivity.     

On the determination of monomer dissociation energies of small water clusters from photoionization experiments

Recently, monomer dissociation energies of neutral water clusters were estimated via a thermodynamic cycle that utilized the measured appearance energies of vacuum ultraviolet (VUV) photoionized water clusters and the previously reported dissociation energies of protonated water clusters. The thermodynamic cycle incorrectly assumed that the energy difference between the (H2O)n+ --> (H2O)n-1H+ + OH* asymptotes (the relaxation energy) was zero. We show that these relaxation energies are large and cannot be neglected in the analysis. Thus, the neutral water cluster monomer dissociation energies cannot be directly determined from the measured ionization potentials because they are themselves involved in the appropriate thermodynamic cycle.     

The spectroscopic signature of the "all-surface" to "internally solvated" structural transition in water clusters in the n = 17-21 size regime

The existence of a transitional size regime where preferential stabilization alternates between "all-surface" (all atoms on the surface of a cluster) and "internally solvated" (one water molecule at the center of the cluster, fully solvated) configurations with the addition or the removal of a single water molecule, predicted earlier with the flexible, polarizable (many-body) Thole-type model interaction potential (TTM2-F), has been confirmed from electronic structure calculations for (H2O)n, n = 17-21. The onset of the appearance of the first "interior" configuration in water clusters occurs for n = 17. The observed structural alternation between interior (n = 17, 19, 21) and all-surface (n = 18, 20) global minima in the n = 17-21 cluster regime is accompanied by a corresponding spectroscopic signature, namely, the undulation in the position of the most redshifted OH stretching vibrations according to the trend: interior configurations exhibit more redshifted OH stretching vibrations than all-surface ones. These most redshifted OH stretching vibrations form distinct groups in the intramolecular region of the spectra and correspond to localized vibrations of donor OH stretches that are connected to neighbors via "strong" (water dimer-like) hydrogen bonds and belong to a water molecule with a "free" OH stretch.     

Using key performance indicators as knowledge-management tools at a regional health-care authority level.

The advantages of the introduction of information and communication technologies in the complex health-care sector are already well-known and well-stated in the past. It is, nevertheless, paradoxical that although the medical community has embraced with satisfaction most of the technological discoveries allowing the improvement in patient care, this has not happened when talking about health-care informatics. Taking the above issue of concern, our work proposes an information model for knowledge management (KM) based upon the use of key performance indicators (KPIs) in health-care systems. Based upon the use of the balanced scorecard (BSC) framework (Kaplan/Norton) and quality assurance techniques in health care (Donabedian), this paper is proposing a patient journey centered approach that drives information flow at all levels of the day-to-day process of delivering effective and managed care, toward information assessment and knowledge discovery. In order to persuade health-care decision-makers to assess the added value of KM tools, those should be used to propose new performance measurement and performance management techniques at all levels of a health-care system. The proposed KPIs are forming a complete set of metrics that enable the performance management of a regional health-care system. In addition, the performance framework established is technically applied by the use of state-of-the-art KM tools such as data warehouses and business intelligence information systems. In that sense, the proposed infrastructure is, technologically speaking, an important KM tool that enables knowledge sharing amongst various health-care stakeholders and between different health-care groups. The use of BSC is an enabling framework toward a KM strategy in health care.     

Breath acetone monitoring by portable Si:WO3 gas sensors

Breath analysis has the potential for early stage detection and monitoring of illnesses to drastically reduce the corresponding medical diagnostic costs and improve the quality of life of patients suffering from chronic illnesses. In particular, the detection of acetone in the human breath is promising for non-invasive diagnosis and painless monitoring of diabetes (no finger pricking). Here, a portable acetone sensor consisting of flame-deposited and in situ annealed, Si-doped epsilon-WO₃ nanostructured films was developed. The chamber volume was miniaturized while reaction-limited and transport-limited gas flow rates were identified and sensing temperatures were optimized resulting in a low detection limit of acetone (∼20 ppb) with short response (10–15 s) and recovery times (35–70 s). Furthermore, the sensor signal (response) was robust against variations of the exhaled breath flow rate facilitating application of these sensors at realistic relative humidities (80–90%) as in the human breath. The acetone content in the breath of test persons was monitored continuously and compared to that of state-of-the-art proton transfer reaction mass spectrometry (PTR-MS). Such portable devices can accurately track breath acetone concentration to become an alternative to more elaborate breath analysis techniques.     

A compound control chart for monitoring and controlling high quality processes

In the present article, we propose a new control chart for monitoring high quality processes. More specifically, we suggest declaring the monitored process out of control, by exploiting a compound rule couching on the number of conforming units observed between the (i − 1)th and the ith nonconforming item and the number of conforming items observed between the (i − 2)th and the ith nonconforming item. Our numerical experimentation demonstrates that the proposed control chart, in most of the cases, exhibits a better (or at least equivalent) performance than its competitors.     

Vapor phase infrared spectroscopy and ab initio fundamental anharmonic frequencies of ammonia borane

The infrared absorption spectrum of ammonia borane vapor has been recorded between 3600 and 600 cm(-1). Of the eleven infrared active fundamental vibrational modes, seven modes of NH(3)(11)BH(3) and four modes of NH(3)(10)BH(3) were observed. The spectra were recorded with sufficient resolution to observe the rotational structure of the bands, which allowed for preliminary least-squares fitting of the band origins and rotational constants. First-principles electronic structure calculations were performed to obtain anharmonic band origins and their intensities. The band assignments are discussed in relation to other spectroscopic techniques that have been previously used to study this molecule. A semi-empirical estimate of the vapor pressure of ammonia borane at room temperature (22 °C) was made and found to be ~1 × 10(-4) Torr. The assignment of the measured modes was aided by the calculated anharmonic frequencies and their infrared intensities. The combination of the CCSD(T) harmonic frequencies with the B3LYP anharmonicities, obtained from second-order vibrational perturbation theory, was found to produce an overall best agreement with the measured band origins.     

A combined gas-phase photoelectron spectroscopic and theoretical study of Zeise's anion and its bromine and iodine analogues

Shining light on Zeise: In a study of Zeise's anion, [PtCl(3)(C(2)H(4))](-), and its bromine and iodine analogues, electronic structure information for each species, derived from spectral features, is assigned through calculations at the coupled cluster level of theory. The calculations indicate that the electron binding energies decrease with halogen size and that there is a synergistic η(2) interaction between C(2)H(4) and the PtX(3)(-) anions.