Proton sponges, continued protonated

From a physical organic point of view, there is continuing debate about whether the enhanced basicity in proton sponges is due mainly to strain relief on protonation, or to the special properties of the hydrogen bonds in their monoprotonated ions. 

Figure 6.3 Stimuli-responsive polymers and their intracellular mechanisms leading to transfection. (A) Cationic polymers containing bioreducible disulfide bonds (S-S) can form tight complexes with DNA, releasing it in the cytosol, due to reduction of disulfide bonds to two thiol groups. (B) Associated polyplexes can he dissociated in the cytosol by temperature decrease, leading to DNA release. (C) The endosomal escape can be promoted by pH-responsive polymers such as PEI that act as proton sponges, preventing the normal acidification of the endosomes the continuous influx of protons, counterions and water eventually leads to endosomal disruption and DNA release.

Scheme 14 The proposed proton sponge mechanism of endosmnal escape. (A) Polyplexes enclosed in an endosrane after endocytosis. (B) Due to the pH buffering in the taidosome, the protons continue to be pumped into the vesicle, resulting in CP influx and an increase in the osmolarity inside the endosomal vesicle. (C) Because of the osmolarity increase, water passes into the endosomal vesicle. (D) The increase in water voltune results in the swelling of the endosomal compartment until it ruptures. (E) Release of the polyplex into the cytoplasm, which leads to nuclear uptake of DNA. Reprinted with permission from [119]. Copyright 2011 Elsevier...

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