Novel neutral imidazole-lipophosphoramides for transfection assays

New helper lipids, possessing an imidazole polar head, have been synthesized and included in formulations for transfection assays; these new helper lipids can improve the transfection by a factor of up to 100 compared to the use of DOPE as co-lipid.     

Stable near-infrared anionic polymethine dyes: structure, photophysical, and redox properties

The concept of cyanine has been successfully extended to an anionic heptamethine dye featuring tricyanofuran (TCF) moieties in terms of structure, reactivity, and photophysical properties. Importantly, absorption and emission are red-shifted compared to its classical cationic analog without any cost in terms of thermal stability. In addition to its "cyanine" behavior, this molecule exhibits further redox properties: oxidation and reduction led to the reversible formation of radical species whose absorption is in marked contrast with that of cyanines.     

Photoactivity and UV absorption spectroscopy of RCo(CO)4 (R = H, CH3) organometallic complexes

The photoactivity of RCo(CO)4 (R = H, CH3) complexes has been investigated and compared by means of state correlation diagrams connecting the low-lying singlet (1)E (d(Co) --> sigma*(Co-R) and d(Co) --> pi*(CO)) and (1)A1 (d(Co) --> pi*(CO)) electronic states accessible through UV irradiation, and the low-lying triplet states ((3)E and (3)A1), to the corresponding states of the primary products R + Co(CO)4 and CO(ax) + RCo(CO)3. The electronic absorption spectra have been calculated by time-dependent wave packet propagations on two-dimensional potential energy surfaces describing both channels of dissociation, namely the homolysis of the R-Co and the CO(ax)-Co bonds. It is shown that the absorption spectrum of HCo(CO)4 is characterized by two peaks; the most intense peaks for each set are located respectively at 42,659 and 45,001 cm(-1). The CH(3)Co(CO)4 absorption spectrum also gives two sets of signals with maximum intensities found at 42,581 and 51,515 cm(-1). These bands for both molecules are assigned to the two metal-to-ligand-charge-transfer (MLCT; d(Co) --> pi*(CO)) states. Three photoactive states have been determined in both molecules, namely the singlet metal-to-sigma-bond-charge-transfer (MSBCT) states (a(1)E and b(1)E), simultaneously dissociative for both the homolysis of CO and the R-Co bond, and the (3)A1 (sigma(Co-R) --> sigma*(Co-R)), dissociative along the R-Co bond.     

Concise Multigram‐Scale Synthesis of Push–Pull Tricyanofuran‐Based Hemicyanines with Giant Second‐Order Nonlinearity: An Alternative for Electro‐optic Materials

Highly stable and highly soluble push–pull heptamethine hemicyanines based on the tricyanofuran electron‐accepting group can be prepared on a 15 g scale. The compounds display giant second‐order nonlinear figure of merit, μβ of up to 31 000×10^?48 esu, and lead to a poled material with a second‐order nonlinear response, r₃₃ of 90 pm V^?1 at 1.06 μm     

Efficient Synthesis of Chiral 1,1′‐Sulfonyl Bisaziridines

An efficient three‐step synthesis of chiral 1,1′‐(sulfonyl)bisaziridines is described. Preparation of these compounds was carried out easily starting from N,N′‐sulfonyl bis‐(α‐L‐aminoester) to afford the title compounds in very good yields. These 1,1′‐(sulfonyl)bisaziridines can constitute interesting synthetic building blocks.     

Solving genetic heterogeneity in extended families by identifying sub-types of complex diseases

The study of genetic properties of a disease requires the collection of information concerning the subjects in a set of pedigrees. The main focus of this study was the detection of susceptible genes. However, even with large pedigrees, the heterogeneity of phenotypes in complex diseases such as Schizophrenia, Bipolar and Autism, makes the detection of susceptible genes difficult to accomplish. This is mainly due to a genetic heterogeneity: many genes phenomena are involved in the disease. In order to reduce this heterogeneity, our idea consists in sub-typing the disease and in partitioning the population into more alike sub-groups. We developed a probabilistic model based on a Latent Class Analysis (LCA) that takes into account the familial dependence inside a pedigree, even for large pedigrees. It also takes into account individuals with missing and partially missing measurements. Estimation of model parameters is performed by an EM algorithm, and computations for the E step inside a pedigree are achieved using a pedigree peeling algorithm. When more than one model are fitted, we use model selection strategies such as cross-validation or/and BIC approaches to choose the suitable model among a set of candidates. Moreover, we present a simulation based on a genetic disease class model and we show that our model leads to better individual classification than the model that assumes independence among subjects. An application of our model to a Schizophrenia-Bipolar pedigree data set from Eastern Quebec is also performed.     

Are the Fluorescent Properties of the Cyan Fluorescent Protein Sensitive to Conditions of Oxidative Stress?

The modifications induced by reactive oxygen species (ROS) on fluorescent proteins (FPs) may have important implications for live cell fluorescence imaging. Using quantitative γ-radiolysis, we have studied the ROS-induced biochemical and photophysical perturbations on recombinant cyan fluorescent protein (CFP). After oxidation by the ˙OH radical, the protein displays a modified RP-HPLC elution profile, while the CFP fluorescence undergoes pronounced decreases in intensity and lifetime, without changes in its excitation and emission spectra. Meanwhile, the Förster resonant energy transfer (FRET) between the single W⁵⁷ and the chromophore remains unperturbed. These results rule out a direct oxidation of the CFP chromophore and of W⁵⁷ as well as major changes in the protein 3D structure, but show that new fluorescent forms associated to a higher level of dynamic quenching have been generated. Thus, strict in situ controls are required when CFP is to be used for FRET studies in situations of oxidative activity, or under strong illumination.