Evaluation of Multivalent Dendrimers Based on Melamine:  Kinetics of Thiol−Disulfide Exchange Depends on the Structure of the Dendrimer

Abstract

The rate of thiol-disulfide exchange of dansyl groups mediated by dithiothreitol depends on the structure of the dendrimer. In general, the rate of exchange decreases as the size of the dendrimer increases. Dendrimers with disulfides attached near the core undergo exchange more slowly than dendrimers with disulfides near the periphery. Exchange is a bimolecular (noncooperative) process between dansyl-linked disulfides and dithiothreitol. No evidence for intramolecular macrocylization (cooperative) exchange is observed. Mass spectrometry is used to follow exchange in two dendrimers, providing qualitative and quantitative information about this process. Mathematical models suggest that the rates for exchange for all disulfides of a dendrimer are similar, but increase as the exchange reaction progresses.

Synthetic regimes due to packing constraints in dendritic molecules confirmed by labelling experiments

“…There is no universal label and the choice of the reagent should be customized to the synthetic chemistry used. When NH 2 groups are involved one may use the Sanger reagent 51,52 or Dansyl [54][55][56] . The Sanger reagent is less prone to aggregation and its smaller size is advantageous at high g. (iv) The labelling method can quantify all free ends for 1rgtg max , that is,…”

Stimuli-responsive nanomaterials for therapeutic protein delivery

“…[47] This thiol-disulfide exchange offers opportunity to achieve programmable drug release utilizing redox potential as trigger. [48] Attributed to the reversible characteristic of thiol-disulfide chemistry, disulfide bonds can be incorporated into either the polymer backbone or the crosslinkers in order to design redox-responsive nanomaterials.…”

Identification of diamine linkers with differing reactivity and their application in the synthesis of melamine dendrimers

“…That is, during a convergent synthesis, protecting group manipulations and functional group interconversions could be avoided because the benzylic amine would react preferentially (essentially exclusively) with the monochlorotriazine dendron being elaborated. 1,[3][4][5][6][7] The low stability of these aniline derivatives required reasonable, but additional, care on handling. While the use of distilled solvents and inert atmospheres are not uncommon, nor is the requirement for refrigerated storage of intermediates, we recognized that these precautions could impact the broader acceptance of these materials.…”

“…1 From these studies, aminomethylpiperidine emerged as a diamine linker of choice and was used extensively. 1,2,7,9,[15][16][17]19,20 Using competition experiments, the relative reactivity difference measured for the cyclic secondary amine and primary amine of aminomethylpiperidine is ~ 20 times. Theoretically, 5% of the product formed might derive from reaction of the monochlorotriazine dendron with the primary amine instead of the desired secondary amine.…”