A pH- and Metal-Actuated Molecular Shuttle in Water.

The structure of the Viologen-Phenylene-Imidazole (VPI) guest, previously shown to be bound by cucurbit[7]uril (CB[7]) with binding modes depending on pH and silver ions, has been extended by adding hydrophobic groups on the two extremities of VPI before investigations of CB[7] binding by NMR, ITC, X-ray diffraction, UV-vis and fluorescence spectroscopies. With an imidazole station extended by a naphthalene group (VPI-N), binding modes of CB[7] are similar to those previously observed. However, with the viologen extended by a tolyl group (T-VPI), CB[7] preferentially sits on station T, shuttling between the T and P stations at acid pH or after Ag+ addition. The CB[7] ⋅ T-VPI complex thus behaves as a metal-actuated thermodynamic stop-and-go molecular shuttle featured by fast and autonomous ring translocation between two stations and a continuum for fractional station occupancy solely and easily controlled by Ag+ concentration.

Controlled oligomeric guest stacking by cucurbiturils in water.

Previously, we reported a guest molecule containing a viologen (V), a phenylene (P) and an imidazole (I) fragment (VPI) forming a host : guest 2 : 2 complex with cucurbit[8]uril (CB[8]) and an unprecedented 2 : 3 complex with cucurbit[10]uril (CB[10]). To better address the structural features required to form these complexes, two VPI analogues were designed and synthesized: the first with a tolyl (T) group grafted on the V part (T-VPI) and the second with a naphthalene (N) fused on the imidazole (I) part (VPI-N). While VPI-N afforded a discrete well-defined 2 : 2 complex with CB[8] and a 2 : 3 complex with CB[10], T-VPI organized also as a 2 : 2 complex with CB[8] but no well-defined complex was obtained with CB[10]. These complexes were studied by NMR spectroscopy, notably DOSY, which allowed us to estimate binding constants for 2 : 2 complex formation with CB[8], pointing to more stable 2 : 2 complexes with more hydrophobic guests. UV-vis and fluorescence spectroscopy confirmed complex formation, suggesting host-stabilized charge-transfer interactions. Therefore, the simple addition of CB[8] or CB[10] enabled us to control the level of guest stacking (dimer or trimer) using relevant pairs of synthetic hosts through spontaneous host : guest quaternary or quinary self-assembly.

Base-Free Generation of Organic Electron Donors from Air-Stable Precursors.

Organic electron donors (OEDs) are powerful reducing agents recognized for their potential in the reduction of challenging substrates and in original applications. Nonetheless, their low stability in atmospheric oxygen or over time complicates their manipulation and storage. To overcome these constraints and enhance OED practicality, new air- and moisture-stable aminopyridinium carboxylate and carbonate precursors were synthesized and thermally activated to generate the potent electron donor in situ. Carboxylate adducts proved to be excellent latent OED systems, enabling the facile and efficient reduction of challenging substrates. Their reduction properties were correlated to their structural characteristics by thermogravimetric and spectroscopic analysis.

Cytochrome c - silver nanoparticle interactions: Spectroscopy, thermodynamic and enzymatic activity studies.

Cytochrome c, an iron containing metalloprotein in the mitochondria of the cells with an oxide/redox property, plays key role in the cell apoptotic pathway. In this study, the interaction of silver nanoparticles (AgNPs) with cytochrome c (Cyt c) was investigated by using a combination of spectroscopic, imaging and thermodynamic techniques, including dynamic light scattering (DLS), ultraviolet-visible (UV-vis) spectroscopy, transmission electron microscopy (TEM), fluorescence spectroscopy, near and far circular dichroism (CD) spectroscopy, and isothermal titration calorimetry (ITC). DLS and UV-vis analysis evidenced the formation of surface complexes of Cyt c on AgNPs. The saturation of surface coverage of AgNPs was observed at 4.36 Cyt c molecules per nm2 of AgNPs. The surface complexation resulted in a promotion of the Ag dissolution overtime. The negative sign of enthalpic (ΔH) contribution suggested that electrostatic forces are indicative forces in the interaction between protein and AgNPs. Moreover, the fluorescence spectra revealed that the conformation of protein was altered around tryptophan (Trp) and tyrosine (Tyr) residues indicating the alteration of the tertiary structure of Cyt c. CD analysis evidenced that the secondary structure of Cyt c was modified under AgNPs-Cyt c interactions and the binding of Cyt c onto AgNPs resulted in remarkable structural perturbation around the active site heme, which in turn alter the protein enzymatic activity. The results of the present study contributed to a deeper insight on the mechanisms of interaction between NPs and biomacromolecules and could help establish the in vivo fate of AgNPs on cellular redox homeostasis.

Mapping Fifteen Trace Elements in Human Seminal Plasma and Sperm DNA.

Studies suggest a relationship between semen quality and the concentration of trace elements in serum or seminal plasma. However, trace elements may be linked to DNA and capable of altering the gene expression patterns. Thus, trace element interactions with DNA may contribute to the mechanisms for a trans-generational reproductive effect. We developed an analytical method to determine the amount of trace elements bound to the sperm DNA, and to estimate their affinity for the sperm DNA by the ratio: R = Log [metal concentration in the sperm DNA/metal concentration in seminal plasma]. We then analyzed the concentrations of 15 trace elements (Al, Cd, Cr, Cu, Hg, Mn, Mo, Ni, Pb, Ti, V, Zn, As, Sb, and Se) in the seminal plasma and the sperm DNA in 64 normal and 30 abnormal semen specimens with Inductively Coupled Plasma/Mass Spectrometry (ICP-MS). This study showed all trace elements were detected in the seminal plasma and only metals were detected in the sperm DNA. There was no correlation between the metals' concentrations in the seminal plasma and the sperm DNA. Al had the highest affinity for DNA followed by Pb and Cd. This strong affinity is consistent with the known mutagenic effects of these metals. The lowest affinity was observed for Zn and Ti. We observed a significant increase of Al linked to the sperm DNA of patients with oligozoospermia and teratozoospermia. Al's reproductive toxicity might be due to Al linked to DNA, by altering spermatogenesis and expression patterns of genes involved in the function of reproduction.

Determination of uremic solutes in biological fluids of chronic kidney disease patients by HPLC assay.

During chronic kidney disease (CKD), solutes called uremic solutes, accumulate in blood and tissues of patients. We developed an HPLC method for the simultaneous determination of several uremic solutes of clinical interest in biological fluids: phenol (Pol), indole-3-acetic acid (3-IAA), p-cresol (p-C), indoxyl sulfate (3-INDS) and p-cresol sulfate (p-CS). These solutes were separated by ion-pairing HPLC using an isocratic flow and quantified with a fluorescence detection. The mean serum concentrations of 3-IAA, 3-INDS and p-CS were 2.12, 1.03 and 13.03 µM respectively in healthy subjects, 3.21, 17.45 and 73.47 µM in non hemodialyzed stage 3-5 CKD patients and 5.9, 81.04 and 120.54 µM in hemodialyzed patients (stage 5D). We found no Pol and no p-C in any population. The limits of quantification for 3-IAA, 3-INDS, and p-CS were 0.83, 0.72, and 3.2 µM respectively. The within-day CVs were between 1.23 and 3.12% for 3-IAA, 0.98 and 2% for 3-INDS, and 1.25 and 3.01% for p-CS. The between-day CVs were between 1.78 and 5.48% for 3-IAA, 1.45 and 4.54% for 3-INDS, and 1.19 and 6.36% for p-CS. This HPLC method permits the simultaneous and quick quantification of several uremic solutes for daily analysis of large numbers of samples.

Binding of p-cresylsulfate and p-cresol to human serum albumin studied by microcalorimetry.

p-Cresylsulfate, a metabolite of p-cresol, is reported as prototypic protein-bound uremic toxin, inefficiently removed by haemodialysis. The binding between p-cresylsulfate or p-cresol and human serum albumin was studied using microcalorimetry. The results confirm that the two molecules are protein-bound. However, the affinity of p-cresylsulfate and p-cresol toward human serum albumin is moderate at 25 degrees C and becomes relatively weak at physiological temperature, 37 degrees C. The binding principally involves van der Waals type interactions, and the binding sites of the two molecules are the same or very close. The low fraction of bound toxin (13-20%) appears to be insufficient to link strong binding to poor removal of this toxin by hemodialysis.