Aryl Boronic Acid Catalysed Dehydrative Substitution of Benzylic Alcohols for C−O Bond Formation

A combination of pentafluorophenylboronic acid and oxalic acid catalyses the dehydrative substitution of benzylic alcohols with a second alcohol to form new C−O bonds. This method has been applied to the intermolecular substitution of benzylic alcohols to form symmetrical ethers, intramolecular cyclisations of diols to form aryl-substituted tetrahydrofuran and tetrahydropyran derivatives, and intermolecular crossed-etherification reactions between two different alcohols. Mechanistic control experiments have identified a potential catalytic intermediate formed between the aryl boronic acid and oxalic acid.     

Microwave-assisted, efficient and regioselective Pd-catalyzed C-phenylation of halopyrimidines

We herein report that flash heating microwave irradiation is a helpful tool in the formation of arylpyrimidines from the corresponding halopyrimidines. The palladium-catalyzed cross-coupling reactions of 2,4-di- and 2,4,5-trihalopyrimidines with phenylboronic acid under the above conditions are described. By use of the appropriate catalyst and the adequate halopyrimidine, good regioselectivity can be achieved in the 2-, 4-, or 5-positions of the heterocycle. In addition, we show that this methodology is ameneable for the stepwise preparation of mono-, di-, and triphenylpyrimidines.     

Inclusion of molybdenocene dichloride (Cp2MoCl2) in 2-hydroxypropyl- and trimethyl-β-cyclodextrin: Structural and biological properties

Organometallic-cyclodextrin inclusion compounds were obtained by the treatment of molybdenocene dichloride (Cp₂MoCl₂) with the modified cyclodextrins (CDs) heptakis-2,3,6-tri-O-methyl-β-CD (TRIMEB) and 2-hydroxypropyl-β-CD (HPβCD) in aqueous solution. The products were isolated by liophilisation and characterised in the solid-state by powder XRD, thermogravimetric analysis, Raman and FTIR spectroscopy, and ¹³C CP MAS NMR spectroscopy. The results are consistent with inclusion of Cp₂MoCl₂, rather than hydrolysis products such as [Cp₂Mo(H₂O)X]⁺ (X = Cl, OH) or [Cp₂Mo(H₂O)₂]²⁺. The pure non-included metallocene Cp₂MoCl₂ and its inclusion compounds with unmodified β-CD, TRIMEB and HPβCD were screened for their potential antiproliferative and cytotoxic activity, in both human cancer and healthy cell lines. Inclusion in CD was found to enhance the cytotoxic effect of Cp₂MoCl₂, with the TRIMEB adduct displaying the highest anti-tumour activity, along with the lowest toxicity towards non-neoplastic cells.     

Coordination modes of 2-hydroxynicotinic acid in second- and third-row transition metal complexes

The new Pd(II), Pt(II), Re(V), Mo(VI) and W(VI) complexes of 2-hydroxynicotinic acid (H₂nicO), trans-[PdCl(HnicO)(PPh₃)₂]·0.75CH₃CN (1), K[PdCl(HnicO)₂]·H₂O (2), [Pd(HnicO)₂(bipy)] (3), cis-[PtCl(HnicO)(PPh₃)₂]·0.75CH₃OH·0.5H₂O (4), [PtCl(HnicO)(bipy)] (5), cis-[ReOI₂(HnicO)(PPh₃)] (6), Na₂[Mo₂O₆(HnicO)₂]·5H₂O (7), Na₂[Mo₄O₁₂(HnicO)₂]·2H₂O (8) and Na₂[W₂O₆(HnicO)₂]·5H₂O (9) have been prepared. The crystal structures of 1 and 4, were determined by X-ray diffraction and show the HnicO⁻ ligand coordinated to palladium or platinum through the nitrogen atom only. Infrared, Raman, ¹H and ¹³C{¹H} NMR spectroscopic data for the complexes are presented and are in agreement with the crystallographic results.     

Synthesis of [1,3]dithiole and spiro[1,3]dithiole thiopyran derivatives of the [1,2]dithiolo[1,4]thiazine ring system

We report the synthesis of some new polysulfur-nitrogen heterocycles by cycloaddition reactions to readily available tricyclic condensed 1,2-dithiole-3-thiones. Thus, treatment of bis[1,2]dithiolopyrrole ketothione 1 with diacyl acetylenes gave the bis-aducts 2a-d. On the other hand, cycloaddition of bis[1,2]dithiolo[1,4]thiazine ketothione 3 with 1 equiv of acyl or diacyl acetylenes gave [1,3]dithiolylidenyl[1,2]dithiolo[1,4]thiazines 4a-f in fair to high yields. Catalysis by scandium triflate was used in the reactions that implied the less reactive dipolarophiles. Treatment of 3 with 2 equiv of DBA gave the bis-aduct 5a, and reaction of 4c with DMAD gave the mixed bis-adduct 5b. Cyclic voltammetry of selected examples showed irreversible processes that were influenced by the electrochemical activity of peripheral groups bonded to the heterocyclic system.     

Theoretical study of alkyl-pi and aryl-pi interactions. Reconciling theory and experiment

Quantum mechanical and quantum mechanical/molecular mechanical calculations in conjunction with continuum solvation models have been used to analyze CH-pi interactions in model systems of aryl- and alkyl-aromatic interactions, as well as in a model folding system designed to study those interactions. High level calculations reproduced accurately the interaction of CH-pi interactions in both alkyl- and aryl-based model systems. Dispersion effects dominate the interaction, but the electrostatics term is also relevant for aryl CH-pi interactions. Theoretical calculations were also used to examine the influence of CH-pi interactions in determining the conformational flexibility of folding models. Finally, a critical comparison of the results obtained from high level calculations on model systems and the experimental data derived for folding models in apolar solvents was carried out, which allowed us to reconcile the apparent discrepancy found between both data.     

A Method for Clustering and Screening of Long-dimensional Chemical Data Based on Fingerprints and Similarity Measurements

A method for the treatment of long-dimensional chemical data arrays is presented in this work with the aim of maximising classification models. The method is based on the construction of fingerprints and the subsequent generation of a similarity matrix. The similarity calculation has been modified through a scaling process to take into account different significance shown by the variables. The method was applied to spectral measurements of wines and several aspects were studied, namely: threshold considered in the construction of fingerprints and patterns, weighting factor used for scaling, normalisation method, etc. The application of both Principal Components Analysis and Soft-Independent Modelling of Class Analogies to the similarity matrices gave better classifications of the information than those obtained using original data.     

Application of molecular absorption properties of horseradish peroxidase for self-indicating enzymatic interactions and analytical methods

In this paper an in depth study is presented of the use of the horseradish peroxidase (HRP) enzyme as a self-indicating biorecognition reagent in UV-vis molecular absorption spectrometry. The HRP/H2O2 reaction mechanism in the absence of an external substrate has been clarified, and the interaction between HRP and glucose oxidase (GOx) has been studied. It has been demonstrated that GOx can act as a substrate of HRP; in both cases the kinetic constants have been obtained and mathematical models have been developed. Second, the HRP/H2O2 reaction is used to follow a H2O2-producing enzymatic reaction, the glucose reaction with GOx being used as a model. As an application of this, two methodologies have been proposed for glucose determination: with or without previous incubation of glucose with GOx. In both cases mathematical models relating HRP absorbance changes to glucose concentration have been developed and tested; both methods have been optimized, analytically characterized, and tested for glucose determination in samples. The methodology described could be applied to other heme-proteins and to other H2O2-producing enzymatic reactions. The models permit the reaction constants to be calculated. From the analytical chemistry point of view the models allow the prediction of the method sensitivity for other analytes involved in this type of reaction if the kinetic constants are known and can be used in the design of optical sensors.     

Tautomeric conjugate acids of 2-aminopyrroles: effect of substituents, solvation and cosolute

The tautomeric preferences of the conjugated acids of 2-aminopyrrole derivatives have been examined both in the gas phase and in aqueous solution by using a combination of quantum mechanical, self-consistent reaction field and Monte Carlo–free-energy perturbation methods. The results show that the nature of substituents, the solvent and the presence of cosolute are relevant factors in modulating the relative stability between the tautomeric conjugate acids protonated at the heterocyclic ring and at the exocyclic amino nitrogen. Thus, attachment of electron-withdrawing groups to the ring, solvation in polar solvents, and the presence of negatively charged cosolutes tend to favor protonation at the exocyclic amino nitrogen. Nevertheless, none of these factors alone suffice to change the tautomeric preference for the ring-protonated forms. The results point out that the concerted occurrence of the three factors is necessary to shift the tautomeric preference towards the conjugated species protonated at the exocyclic nitrogen.Contribution to the Jacopo Tomasi Honorary Issue