Analysis of basic compounds at high pH values by reversed-phase liquid chromatography

Reversed phase high performance liquid chromatography (RPLC) is currently the method of choice for the analysis of basic compounds. However, with traditional silica materials, secondary interactions between the analyte and residual silanols produce peak tailing which can negatively affect resolution, sensitivity, and reproducibility. In order to reduce these secondary interactions, which comprise ion exchange, hydrogen bonding, and London forces interactions, chromatographic analyses can be carried out at low or high pH values where silanol groups and basic compounds are mostly uncharged. The chromatographic behaviour of a particular bidentate stationary phase, Zorbax Extend C18, was studied with a set of basic and neutral compounds. Thanks to a higher chemical stability than traditional silica based supports, analyses were carried out with a high pH mobile phase, which represents a good alternative to the acidic mobile phases generally used to reduce ion exchange interactions. The performance of this bidentate stationary phase was also compared with that of other supports and it was proved that it is advantageous to work with high pH mobile phases when analyzing basic compounds.     

New stereoselective preparation of (Z)-3-perfluoroalkyl-3-magnesiated enoates by an iodine-magnesium exchange reaction

(Z)-Ethyl-3-perfluoroalkyl-3-magnesiated crotonates were prepared from (Z)-ethyl-3-perfluoroalkyl-3-iodo enoates by iodine-magnesium exchange reaction with isopropylmagnesium bromide in THF at -78 degrees C. These new reagents reacted with a range of electrophiles, leading to polyfunctional products bearing a perfluoroalkyl group.     

Two-photon absorption in quadrupolar pi-conjugated molecules: influence of the nature of the conjugated bridge and the donor-acceptor separation

Quadrupolar-type substitution of pi-conjugated chromophores with donor and acceptor groups has been shown to increase their two-photon absorption (TPA) response by up to two orders of magnitude. Here, we apply highly correlated quantum-chemical calculations to evaluate the impact of the nature of conjugated bridge and the charge-transfer distance on that enhancement. We compare chromophores with phenylenevinylene-, thienylenevinylene-, polyene-, and indenofluorene-type backbones substituted by dimethylamino and cyano groups. In all compounds, we find a strongly TPA-active A(g) state (either 2A(g) or 3A(g)) in the low-energy region, as well as a higher lying TPA-active state (mA(g)) at close to twice the energy of the lowest lying one-photon allowed state; the smaller energy detuning in the mA(g) states results in very large TPA cross sections delta. We also investigate the influence of the degree of ground-state polarization on TPA. Independent of the nature of the backbone and the donor-acceptor separation, delta displays the same qualitative evolution with a maximum before the cyanine-like limit; the highest TPA cross sections are calculated for distirylbenzene- and polyene-based systems.     

Chemistry of the versatile (hydroxymethyl)phosphinyl P(O)CH2OH functional group

(Hydroxymethyl)phosphorus compounds are well-known and valuable compounds in general; however the use of (hydroxymethyl)phosphinates R(1)P(O)(OR(2))CH(2)OH in particular has been much more limited. The potential of this functionality has not yet been fully realized because the mild unmasking of the hydroxymethyl group was not available. The mild oxidative conversion of R(1)P(O)(OR(2))CH(2)OH into R(1)P(O)(OR(2))H using the Corey-Kim oxidation is described. Other reactions preserving the methylene carbon are also reported.     

Synthesis of a new family of acyclic nucleoside phosphonates, analogues of TPases transition states

A 6-step procedure was developed for the synthesis of a new family of acyclic nucleoside phosphonates (ANPs), "PHEEPA" [(2-pyrimidinyl-2-(2-hydroxyethoxy)ethyl)phosphonic acids] in overall yields ranging from 4.5% to 32%. These compounds, which possess on one side a hydroxy function and on the other side a phosphonate group, can be considered either as potential antiviral agents or as transition state analogues of nucleoside phosphorylases such as thymidine phosphorylase.     

2-Trimethylsilylethyl sulfides in the von Braun cyanogen bromide reaction: selective preparation of thiocyanates and application to nucleoside chemistry

Mixed 2-(trimethylsilyl)ethyl sulfides were synthesized and used in the von Braun cyanogen bromide reaction for preparing selectively thiocyanates in high yield. We show here that this cleavage reaction is highly selective in methanol in comparison with the reaction of the corresponding non-silyl sulfide analogues. This reaction was applied to the synthesis of nucleosidic thiocyanates such as the new nucleosides 14 and 18 in the search for mechanism-based inhibitors of ribonucleoside diphosphate reductase and bioactive molecules. The selective cleavage is possible for sulfides bearing hydroxyl functions and aromatic rings. The reactions of cyanogen bromide as cyanating and brominating agent were observed for the first time under the same conditions with the naphthoxyhexyl 2-trimethylsilylethyl sulfide 7, which, treated with cyanogen bromide in dichloromethane, led selectively to the p-bromonaphthoxyhexyl thiocyanate 10 in 89% yield. Another reaction induced by cyanogen bromide was observed in dichloromethane with the 2-(trimethylsilylethyl)thio nucleoside 13, which gives the corresponding symmetrical disulfide 21 in good yield.     

Corniculoside,a New Biosidic Ester Secoiridoid from Halenia corniculata

Chemical screening of the secondary metabolites from Halenia corniculata L. (CORNAZ ), by LC/UV,LC/TSP-MS (thermospray), and LC/ES-MS (electrospray) was used for the targeted isolation of corniculoside ( 1 ), a new biosidic ester secoiridoid. The structure was established as 7-β-[(E)-4′-O-(β-D -glucopyranosyl)caffeoyloxy]-sweroside by 1D- and 2D-NMR, LC/UV, LC/MS, and FAB-MS data, in combination with chemical reactions.     

The conformation of amine- and amide-terminated poly(propylene imine) dendrimers as investigated by molecular simulation methods

The parameters that influence the conformation of poly(propylene imine) dendrimers were investigated by molecular simulations using molecular mechanics and simulated annealing methods. Dendrimers with two types of peripheral units able to communicate via hydrogen bonding-amine and amide moieties-were considered in order to study the role that secondary interactions among the end groups have in the spatial organization of the dendritic branches. Radial atomic density profiles and radial atomic probability distributions were used to extract global properties, such as the degree of packing of the branches, the distribution of the monomers throughout the molecular volume, and the extent and characteristics of the surface region. Information was also obtained about the nature, location, and extent of formation of the hydrogen bonds, as well as their evolution with dendrimer generation and their assembly into networks. The analyses were supported by a detailed investigation of the first two generations, with an emphasis on the relationship between hydrogen bonding and the compactness and stability of the molecules; this allowed us to account for the generational evolution of hydrogen bonding that is experimentally observed in several poly(propylene imine) dendrimers.     

Delocalization in platinum-alkynyl systems: a metal-bridged organic mixed-valence compound

A complex featuring two triarylamine redox centers bridged by Pt, trans-bis(triethylphosphine)-bis{4-[bis(4-methoxyphenyl)amino]phenylethynyl} platinum(II), has been synthesized as a model system for pi-conjugated Pt-containing polymers. Analysis of the intervalence charge-transfer band displayed by its mixed-valence monocation affords a quantitative assessment of electronic delocalization through the Pt bridge; this is found to be only slightly smaller than that determined for a benzene-bridged analogue. These results are supported by density functional theory calculations, which show that the active orbitals involved in the electron-transfer process in both cases have similar delocalization through the bridging unit.