Synthesis of the First Poly(diaminosulfide)s and an Investigation of Their Applications as Drug Delivery Vehicles

Abstract

This paper reports the first examples of poly(diaminosulfide)s that were synthesized by the reaction of a sulfur transfer reagent and several secondary diamines. The diaminosulfide group has the general structure of R2N-S-NR2 and, although it has been used in the synthesis of small molecules, it has never been utilized in the synthesis of macromolecules until this report. A series of poly(diaminosulfide)s were synthesized at elevated temperatures, and the molecular weights of the polymers were as high as 12,400 g mol−1 with conversions for the polymerization reaction up to 99%. The rate constants for the transamination reactions that lead to the polymers were measured in several solvents to provide an understanding the reaction conditions necessary to polymerize the monomers. The degradation of diaminosulfides were studied in D2O, C6D6, CD3OD, CDCl3, and DMSO-d6/D2O to demonstrate that they were very stable in organic solvents but degraded within hours under aqueous conditions. These results clearly demonstrated that diaminosulfides are very stable in organic solvents under ambient conditions. Poly(diaminosulfide)s have sufficient stabilities to be useful for many applications. The ability of these polymers to function as drug delivery vehicles were studied by the fabrication of nanoparticles of a water-insoluble poly(diaminosulfide) with a dye. The microparticles were readily absorbed into human embryonic 293 cells and possessed no measureable toxicity towards these same cells.

Diaminosulfide based polymer microparticles as cancer vaccine delivery systems

“…Synthesis of poly(4,4′-trimethylenedipiperdyl sulfide) (PNSN) was carried out by a method described previously [29]. Briefly, dimethylamine (8.01 g) in anhydrous ether (400 mL) was first cooled to −78°C for 44 min.…”

“…The manufacture of poly-(diaminosulfide)s (PNSN) in the form of macromolecules has only recently been reported and biodegradable particles made from these polymers were shown to possess low cytotoxicity [29, 30]. PNSN polymers are characterized by having a NSN linkage (R 2 NSNR 2 ) along the backbone and, unlike most polymers, inorganic functional groups are involved in the polymerization reaction (Figure 1).…”

“…PNSN polymers are characterized by having a NSN linkage (R 2 NSNR 2 ) along the backbone and, unlike most polymers, inorganic functional groups are involved in the polymerization reaction (Figure 1). The diaminosulfide functional group degrades at comparable rates to ester bonds at neutral pH, but at much faster rates under acidic conditions [29, 31]. This has the potential advantage of providing triggered or accelerated release of cargo when phagocytosed particles experience lower pH conditions within phagosomal locations of dendritic cells.…”

Polymerizations with elemental sulfur: A novel route to high sulfur content polymers for sustainability, energy and defense

“…4d), and rate of S 8 consumption was observed to dominate in the initial stages over vinylic polymerization [51]. More recently Bowden et al developed a new class of sulfur containing polymers based upon poly(aminosulfides) [52][53][54].…”

New Class of Biodegradable Polymers Formed from Reactions of an Inorganic Functional Group

“…35–40 In a recent article we reported on the synthesis of the first polydiaminosulfides based on the diaminosulfide functional group (R 2 N-S-NR 2 ). 41 The diaminosulfide functional group differs from the sulfenamide functional group in its structure, reactivity, and reaction products. A loose analogy to explain the differences between diaminosulfides and sulfenamides is to compare this pair to esters and anhydrides.…”