In the context of gene delivery, chitosan has been widely used as a safe and effective polycation to complex DNA, RNA and more recently, siRNA. However, much less attention has been paid to chitosan oligosaccharides (COS) despite their biological properties. This study proposed to carry out a physicochemical study of COS varying in degree of polymerization (DP) from 5 to 50, both from the point of view of the solution properties and the complexing behavior with siRNA. The main parameters studied as a function of DP were the apparent pKa, the solubility versus pH, the binding affinity with siRNA and the colloidal properties of complexes. Some parameters, like the pKa or the binding enthalpy with siRNA, showed a marked transition from DP 5 to DP 13, suggesting that electrostatic properties of COS vary considerably in this range of DP. The colloidal properties of siRNA/COS complexes were affected in a different way by the COS chain length. In particular, COS of relatively high DP (≥50) were required to form small complex particles with good stability.
Arylidene
acetals are widely used protecting groups, because of
not only the high regioselectivity of their introduction but also
the possibility of performing further regioselective reductive opening
in the presence of a hydride donor and an acid catalyst. In this context,
the Et3SiH/PhBCl2 system presents several advantages:
silanes are efficient, environmentally benign, and user-friendly hydride
donors, while PhBCl2 opens the way to unique regioselectivity
with regard to all other Brønsted or Lewis acids used with silanes.
This system has been extensively used by several groups, and we have
demonstrated its high regioselectivity in the reductive opening of
4,6- and 2,4-O-p-methoxybenzylidene
moieties in protected disaccharides. Surprisingly, its use on 4,6-O-benzylidene-containing substrates 1 and 2 led to unreproducible yields due to the unexpected formation
of several side products. Their characterizations allowed us to identify
different pitfalls potentially affecting the outcome of reductive
opening of arylidenes with the Et3SiH/PhBCl2 reagent system: alkene hydroboration, azide reduction, and/or Lewis
acid-promoted cleavage of the arylidene. With this knowledge, we optimized
reproducible and high-yielding reaction conditions that secure and
extend the scope of the Et3SiH/PhBCl2 system
as a reagent for the regioselective opening of arylidenes in complex
and multifunctional molecules.
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