Cell-specific, activatable, and theranostic prodrug for dual-targeted cancer imaging and therapy

Herein we describe the design and synthesis of a folate-doxorubicin conjugate with activatable fluorescence and activatable cytotoxicity. In this study we discovered that the cytotoxicity and fluorescence of doxorubicin are quenched (OFF) when covalently linked with folic acid. Most importantly, when the conjugate is designed with a disulfide bond linking the targeting folate unit and the cytotoxic doxorubicin, a targeted activatable prodrug is obtained that becomes activated (ON) within the cell by glutathione-mediated dissociation and nuclear translocation, showing enhanced fluorescence and cellular toxicity. In our novel design, folic acid acted as both a targeting ligand for the folate receptor as well as a quencher for doxorubicin's fluorescence.     

Essential amino acids interacting with flavonoids: A theoretical approach

The interaction of two flavonoid species (resorcinolic and fluoroglucinolic) with the 20 essential amino acids was studied by the multiple minima hypersurface (MMH) procedures, through the AM1 and PM3 semiempirical methods. Remarkable thermodynamic data related to the properties of the molecular association of these compounds were obtained, which will be of great utility for future investigations concerning the interaction of flavonoids with proteins. These results are compared with experimental and classical force field results reported in the available literature, and new evidences and criteria are shown. The hydrophilic amino acids demonstrated high affinity in the interaction with flavonoid molecules; the complexes with lysine are especially extremely stable. An affinity order for the interaction of both flavonoid species with the essential amino acids is suggested. Our theoretical results are compared with experimental evidence on flavonoid interactions with proteins of biomedical interest. © 2005 Wiley Periodicals, Inc. Int J Quantum Chem, 2005     

The assembly state between magnetic nanosensors and their targets orchestrates their magnetic relaxation response

The target-induced clustering of magnetic nanoparticles is typically used for the identification of clinically relevant targets and events. A decrease in the water proton transverse NMR relaxation time, or T(2), is observed upon clustering, allowing the sensitive and accurate detection of target molecules. We have discovered a new mechanistically unique nanoparticle-target interaction resulting in a T(2) increase and demonstrate herein that this increase, and its associated r(2) relaxivity decrease, are also observed upon the interaction of the nanoparticles with ligands or molecular entities. Small molecules, proteins, and a 15-bp nucleic acid sequence were chemically conjugated to polyacrylic-acid-coated iron oxide nanoparticles, and all decreased the original nanoparticle r(2) value. Further experiments established that the r(2) decrease was inversely proportional to the number of ligands bound to the nanoparticle and the molecular weight of the bound ligand. Additional experiments revealed that the T(2)-increasing mechanism was kinetically faster than the conventional clustering mechanism. Most importantly, under conditions that result in T(2) increases, as little as 5.3 fmol of Bacillus anthracis plasmid DNA (pX01 and pX02), 8 pmol of the cholera toxin B subunit (Ctb), and even a few cancer cells in blood were detected. Transition from the binding to the clustering mechanism was observed in the carbohydrate-, Ctb-, and DNA-sensing systems, simply by increasing the target concentration significantly above the nanoparticle concentration, or using Ctb in its pentameric form as opposed to its monomer. Collectively, these results demonstrate that the molecular architectures resulting from the interaction between magnetic nanosensors and their targets directly govern water proton NMR relaxation. We attribute the observed T(2) increases to the bound target molecules partially obstructing the diffusion of solvent water molecules through the superparamagnetic iron oxide nanoparticles' outer relaxation spheres. Finally, we anticipate that this novel interaction can be incorporated into new clinical and field detection applications, due to its faster kinetics relative to the conventional nanoparticle-clustering assays.     

N-borane adducts of oxazolidines derived from ephedrine and pseudo- ephedrine. Study of stereochemistry by nuclear magnetic resonance

A series of stable N-borane-oxazolidine adducts has been prepared in high yield from the reaction of 4-methyl-5- phenyl-oxazolidines with BH₃.DMS. The configurations of all compounds were unambiguously assigned by¹H,¹¹ B and¹³C NMR spectroscopy. Isolation of one pair of N-epimers from ephedrine and another pair from pseudoephedrine let us consider and discuss their stereochemical and spectroscopy relationship.     

Obtention de 3 types de derives du bore: esters aminoboriques tris n-boranes,esters amio boriques bis n-boranes et aminalcools n-boranes a partir de la reaction d'aminalcools-1,2 avec BH3.THF et BH3DMS. mise en evidence d'une coordination interner B←N

The reactions of 1,2-aminoalcohols with BH₃.THF or DMS lead to various title compounds, depending on the reaction conditions. The structures have been determined using ¹¹B, ¹H nmr and i.r. spectroscopy and selected reactions. The conclusions differ from previous r$\text{e}$sults: we were in particular able to evidence intramolecular N←B coordination in structures of type $\text{d}$ and $\text{e}$.     

Spiroborates derived from catecholborane and ephedrine type aminoalcohols - model compounds for the study of intramolecular N→B coordination by dynamic 1H-, 11B- and 13C-NMR.

A convenient synthesis of the title compounds is reported. These serve as models to study intramolecular N→B coordination by means of dynamic NMR spectroscopy (¹H, ¹¹B, ¹³C). Steric interactions between substituents at the boroxazolidine ring (C(5)Ph, C(4)Me, NMe) determine the stability of the N→B bond and the nitrogen configuration.