Polymers with acyl-protected perthiol chain termini as convenient building blocks for doubly responsive H₂S-donating nanoparticles

Abstract

H2S-releasing polymers with an acyl-protected perthiol chain terminus were prepared using a simple, high yielding end-group modification process.

Development of a shape‐controlled H2S delivery system using epoxide‐functional nanoparticles

“…S5). The new proton resonances are consistent with those observed for the corresponding small molecule H 2 S donors as well as SS(C=O)Ph end‐functional polymers …”

“…We reason that such coupled polymeric biproducts which form during the reaction of SS(CO)Ph groups with cysteine may also create an impenetrable environment for further thiol attack. Furthermore, higher molecular weight coupled products are formed during the synthesis of spherical and worm‐like micelles ( 3a and 4a ) which could also enhance this effect …”

“…We have also previously reported a self‐assembling poly(ethylene glycol)–cholesterol conjugate incorporating a garlic‐inspired trisulfide linkage between the two segments that releases H 2 S in the presence of thiols (even at intracellular levels), with concomitant changes to solubility . Further, by installing an H 2 S donor moiety (i.e., an acyl‐protected perthiol) on the end group of a block copolymer, we have demonstrated that the release of H 2 S from the associated micelles can be modulated . More recently, Matson and coworkers have described the development of peptide–H 2 S donor conjugates (PHDCs) that self‐assemble into nanoribbons or rigid nanocoils, dependent upon the specific PDHC used .…”

“…Herein, we report the preparation of shape controlled H 2 S releasing nanoparticles by combining PISA with post‐polymerization transformation of poly(GMA) (PGMA) units in the particle corona. Specifically, we have incorporated acyl‐protected perthiol groups (H 2 S donors) by transformation of pendant epoxide groups using a variant of our previously reported approach for end‐group modification . Initially, copolymer and self‐assembled nanoparticles with different morphologies (spherical and worm‐like micelles) containing GMA groups were prepared via reversible addition–fragmentation chain transfer (RAFT) polymerization, after which the GMA groups were converted into benzoyl‐protected perthiol groups using a series of sulfhydryl modification reactions.…”

The Benefits of Macromolecular/Supramolecular Approaches in Hydrogen Sulfide Delivery: A Review of Polymeric and Self-Assembled Hydrogen Sulfide Donors

“…In 2017, Quinn and coworkers reported on H 2 S-releasing micelles from perthioester-containing polymer constructs synthesized via RAFT polymerization with facile end-group modification (Fig. 2E) (111). The benzyl dithioester chain end was first functionalized with pyridyl disulfide groups and subsequently reacted with thiobenzoic acid to yield polymers with benzoyl-capped perthiol x-chain ends.…”