Scanning electrochemical cell microscopy is introduced as a new tool for the synthesis and deposition of polymers on SAM-functionalised Au surfaces. The deposition of poly(N-hydroxyethyl acrylamide) is shown to be enhanced through the electrochemical generation of activating Cu(I)Cl/Me6TREN catalyst. Initiation of the polymerisation reaction is most likely due to in situ generation of reactive oxygen species following oxygen reduction.

The entropy-driven affinity of trivalent (in)organic arsenicals for closely spaced dithiols has been exploited to develop a novel route to peptide/protein–polymer conjugation. A trivalent arsenous acid (As(III)) derivative (1) obtained from p-arsanilic acid (As(V)) was shown to readily undergo conjugation to the therapeutic peptide salmon calcitonin (sCT) via bridging of the Cys1-Cys7 disulfide, which was verified by RP-HPLC and MALDI-ToF-MS. Conjugation was shown to proceed rapidly (t < 2 min) in situ and stoichiometrically through sequential reduction–conjugation protocols, therefore exhibiting conjugation efficiencies equivalent to those reported for the current leading disulfide-bond targeting strategies. Furthermore, using bovine serum albumin as a model protein, the trivalent organic arsenical 1 was found to demonstrate enhanced specificity for disulfide-bond bridging in the presence of free cysteine residues relative to established maleimide functional reagents. This specificity represents a shift toward potential orthogonality, by clearly distinguishing between the reactivity of mono- and disulfide-derived (vicinal or neighbors-through-space) dithiols. Finally, p-arsanilic acid was transformed into an initiator for aqueous single electron-transfer living radical polymerization, allowing the synthesis of hydrophilic arsenic-functional polymers which were shown to exhibit negligible cytotoxicity relative to a small molecule organic arsenical, and an unfunctionalized polymer control. Poly(poly[ethylene glycol] methyl ether acrylate) (PPEGA480, DPn = 10, Mn,NMR = 4900 g·mol–1, Đ = 1.07) possessing a pentavalent arsenic acid (As(V)) α-chain end was transformed into trivalent As(III) post-polymerization via initial reduction by biological reducing agent glutathione (GSH), followed by binding of GSH. Conjugation of the resulting As(III)-functional polymer to sCT was realized within 35 min as indicated by RP-HPLC and verified later by thermodynamically driven release of sCT, from the conjugate, in the presence of strong chelating reagent ethanedithiol.

Ligand mediated termination events occur during the homo-polymerisation of methyl (MA) and butyl (BA) acrylate under SET-LRP (Cu(0) mediated) conditions. Careful optimization of [initiator]/[ligand] (Me6Tren) ratios is required to reduce termination in order to achieve optimum polymerisation.

Scanning electrochemical cell microscopy is introduced as a new tool for the synthesis and deposition of polymers on SAM-functionalised Au surfaces. The deposition of poly(N-hydroxyethyl acrylamide) is shown to be enhanced through the electrochemical generation of activating Cu(I)Cl/Me6TREN catalyst. Initiation of the polymerisation reaction is most likely due to in situ generation of reactive oxygen species following oxygen reduction.