On Graphlike k-Dissimilarity Vectors

Let \({\mathcal{G} = (G, w)}\) be a positive-weighted simple finite connected graph, that is, let G be a simple finite connected graph endowed with a function w from the set of edges of G to the set of positive real numbers. For any subgraph \({G^\prime}\) of G, we define \({w(G^\prime)}\) to be the sum of the weights of the edges of \({G^\prime}\) . For any i ₁, . . . , i _k vertices of G, let \({D_{\{i_1,..., i_k\}} (\mathcal{G})}\) be the minimum of the weights of the subgraphs of G connecting i ₁, . . . , i _k . The \({D_{\{i_1,..., i_k\}}(\mathcal{G})}\) are called k-weights of \({\mathcal{G}}\) . Given a family of positive real numbers parametrized by the k-subsets of {1, . . . , n}, \({{\{D_I\}_{I} \in { \{1,...,n\} \choose k}}}\) , we can wonder when there exist a weighted graph \({\mathcal{G}}\) (or a weighted tree) and an n-subset {1, . . . , n} of the set of its vertices such that \({D_I (\mathcal{G}) = D_I}\) for any \({I} \in { \{1,...,n\} \choose k}\) . In this paper we study this problem in the case k =  n?1.     

The role of chemometrics in single and sequential extraction assays: a review. Part II. Cluster analysis, multiple linear regression, mixture resolution, experimental design and other techniques

Single and sequential extraction procedures are used for studying element mobility and availability in solid matrices, like soils, sediments, sludge, and airborne particulate matter. In the first part of this review we reported an overview on these procedures and described the applications of chemometric uni- and bivariate techniques and of multivariate pattern recognition techniques based on variable reduction to the experimental results obtained. The second part of the review deals with the use of chemometrics not only for the visualization and interpretation of data, but also for the investigation of the effects of experimental conditions on the response, the optimization of their values and the calculation of element fractionation. We will describe the principles of the multivariate chemometric techniques considered, the aims for which they were applied and the key findings obtained. The following topics will be critically addressed: pattern recognition by cluster analysis (CA), linear discriminant analysis (LDA) and other less common techniques; modelling by multiple linear regression (MLR); investigation of spatial distribution of variables by geostatistics; calculation of fractionation patterns by a mixture resolution method (Chemometric Identification of Substrates and Element Distributions, CISED); optimization and characterization of extraction procedures by experimental design; other multivariate techniques less commonly applied.     

N-Demethyl-sauroxine,a novel Lycodine Group alkaloid from Huperzia saururus

The present study describes the isolation and identification of N-demethyl-sauroxine, a novel Lycopodium alkaloid obtained from Huperzia saururus (Lam.) Trevis. (Lycopodiaceae). Its structure and relative stereochemistry were elucidated on the basis of its spectral data and chemical correlations. Additionally, acetylcholinesterase inhibitory activity was evaluated (IC₅₀ = 209.6 ± 1.1 μM). The structure of the already identified alkaloid sauroxine was also re-validated through two dimensional NMR data.     

Determination and assessment of the contents of essential and potentially toxic elements in Ayurvedic medicine formulations by inductively coupled plasma-optical emission spectrometry

Traditional Ayurvedic remedies are easily available nowadays not only in India, their country of origin, but also in Western countries. Some of these products contain high concentrations of potentially toxic elements as main or secondary ingredients, in addition to elements essential for human health; for these reasons, it is interesting to determine their elemental composition. In this study we assessed the concentrations of fifteen elements (Al, As, Ca, Cd, Cr, Cu, Fe, Hg, K, Mg, Mn, Na, Pb, Si and Zn) in five products of the Parpati family, a group of Ayurvedic medicines containing high concentrations of mercury, manufactured in various places in India. Concentrations were determined by inductively coupled plasma-optical emission spectrometry (ICP-OES) or (for Pb and Cd) by graphite furnace atomic absorption spectrometry (GF-AAS) after sample mineralization. We compared the calculated daily intake of each element with reference values, considering maximum tolerable intake levels or recommended nutrient amounts. The experimental results were treated with chemometric pattern recognition techniques. We found differences in the composition of products of the same denomination manufactured by different companies and strong correlations among groups of variables. As expected, the daily intake of mercury upon consumption of Parpati medicines largely exceeded the tolerable intake level of this element.     

Regioselective N‐Alkylation of Ethyl 4‐Benzyloxy‐1,2,3‐triazolecarboxylate: A Useful Tool for the Synthesis of Carboxylic Acid Bioisosteres

Acidic 4‐hydroxy‐1,2,3‐triazole is a proven bioisostere of acidic functions that has recently been used to replace the acidic moieties of biologically active leads. Straightforward chemical strategies for the synthesis of the three possible N‐alkylated 4‐hydroxy‐1,2,3‐triazole regioisomers have been designed and reported herein, by identifying the optimal conditions under which the alkylation of ethyl 4‐benzyloxy‐1,2,3‐triazolecarboxylate (compound 19 ) can be regiodirected to the triazole N(b) position and thus produce the only isomer that cannot be obtained via the cycloaddition reaction. Furthermore, an innovative platform for parallel synthesis, called Arachno and which has been patented by the authors' group, has been used to speed up the process, and an NMR study has been carried out to better understand the reactivity of compound 19 towards the N(b) position. A library of benzyloxy protected 4‐hydroxy‐1,2,3‐triazoles has been prepared using the two strategies: regiodirection for the N(b) and N(c) isomers and cycloaddition for the N(a) isomers; the processes are described herein. The three N‐alkylated regioisomer series have been characterized spectroscopically (NMR and MS). The subsequent catalytic hydrogenation of the 4‐benzyloxy protective group on the N‐alkylated‐4‐benzyloxy‐5‐ethoxycarbonyl‐1,2,3‐triazoles provided the corresponding substituted 4‐hydroxy‐1,2,3‐triazoles.     

Enzymatic Approach to and Odor Description of the Twelve Enantiomerically Pure Isomers of Pelargene®

Pelargene^® is a commercial fragrance sold as a mixture of three regioisomeric pyran derivatives ( 1 – 3 ). The enantiomers of each of the two possible diastereoisomers of 1 – 3 were prepared by means of a biocatalyzed approach, and the odor properties of the twelve isolated stereoisomers were evaluated.     

The use of sequential extraction procedures for the characterization and management of contaminated soils

Metal mobility and availability in solid samples, such as soils, sediments and sludges, is frequently studied with sequential extraction procedures, which allow to partition the total metal content into classes of different reactivity. From the experimental point of view, each extraction step requires many practical operations, which can represent sources of error if they are not properly executed. The first part of the paper gives indication on how to perform sequential extractions, from sample pretreatment to extract analysis, in order to reduce experimental errors. The second part describes the main applications of sequential extraction schemes for the characterization and management of contaminated soils: the assessment of the risks associated to metal pollution, the evaluation of the feasibility and efficiency of remediation techniques, the study of soil properties and of metal behaviour and plant availability.     

Formulation and Preliminary in vivo Testing of Rufloxacin-Cyclodextrin Ophthalmic Solutions

Aim of the present work was to investigate the effect of somecyclodextrins (CDs) on the solubility and ocular bioavailability of rufloxacin base (RUF), with theultimate goal of developing an ophthalmic formulation. Phase solubility studies of RUF inpH 7.4 buffer were carried out in the presence of -cyclodextrin (-CD),hydroxypropyl--cyclodextrin (HP--CD) and -cyclodextrin(-CD). The effect of hydroxypropyl methylcellulose (HPMC) on RUF solubility was evaluated after heating the solutionscontaining HP--CD at 120 °C.A significant enhancement of RUF solubility was achieved by associatingthe drug with CDs, particularly HP--CD. This CD formed with RUF a less stablecomplex than that formed by -CD, but did not suffer the solubility limitations ofthe parent CD, and showed a higher solubilizing capacity than -CD. Addition of 0.25%(w/v) HPMC to solutions containing HP--CD increased the solubilizing effect of this CD,thus allowing reduction of the amount necessary for solubilization of 0.3% (w/v) RUF.Preliminary pharmacokinetic data in rabbits indicated that theocular bioavailability of 0.3% (w/v) RUF solubilized by HP--CD was higher when compared witha 0.3% (w/v) RUF suspension used as reference.     

Simulating the active sites of copper-trafficking proteins. Density functional structural and spectroscopy studies on copper(I) complexes with thiols,carboxylato, amide and phenol ligands

A series of mononuclear binary and ternary Cu(I) complexes with formato, formamide, methylphenol, and methanethiolato ligands were optimized at DFT-B3LYP/6-31G** (BS1) and DFT-B3LYP/6-311++G** (BS2) levels of theory. The solvent effect was taken into account via PCM method (BS1W and BS2W, respectively). The coordination arrangement for [Cu^I(SCH₃/S(H)CH₃)(OOCH)]^?/0 and [Cu^I(SCH₃/S(H)CH₃)(O(H)(C₆H₄)CH₃)]^0/+ was pseudo-linear and for [Cu^I(SCH₃/S(H)CH₃)(OOCH)(OC(H)NH₂)]^?/0 was pseudo-trigonal. The [Cu^I(S-S(H)CH₃/Cu^I(S-SCH₃)]^+/0 link even to amide carbonyl and to general O(H)R residues (R=C₆H₅CH₃). [Cu^I(SCH₃)₂(O(H)(C₆H₄)CH₃)]^? went towards dissociation of the O(H)(C₆H₄)CH₃ ligand, whereas [Cu^I(S(H)CH₃)₂(O(H)(C₆H₄)CH₃)]⁺ converged nicely, maintaining the hydroxy function linked to the metal. The trends of total electronic energies seemed to be significant, suggesting that linear Cu^IS₂ coordination is more suitable than Cu^IS, Cu^IS₃ and Cu^IS₄ arrangements. The formation energies of [Cu^I(S(H)CH₃/SCH₃)(OOCH)]^0/?1 were higher than those of [Cu^I(S(H)CH₃/SCH₃)₂]^+/? on starting from [Cu^I(S(H)CH₃/Cu^I(SCH₃)]^+/0 by ca. 11–9 kcal mol^?1 (BS2W). The structural arrangements, bond distances, and angles as well as computed spectroscopic parameters resulted in good agreement with experimental data for corresponding synthetic complexes and with metal site regions of several copper(I)-proteins. These data help in interpreting structural data of complex biological systems and in constructing reliable force fields for molecular mechanics computations.