Efficient Synthesis of Isoxazolidine-Tethered Monolayer-Protected Gold Nanoparticles (MPGNs) via 1,3-Dipolar Cycloadditions under High-Pressure Conditions

Abstract

A maleimide-modified 2.5 +/- 0.5 nm mixed monolayer protected gold nanoparticle (2-C(12)MPGN) containing approximately 30% maleimide-terminated dodecanethiolate/dodecanethiolate ligands was prepared. The 2-C(12)MPGN was reacted with a series of nitrones (a-i) at both atmospheric and hyperbaric (11 000 atm) conditions to form the corresponding isoxazolidine-modified nanoparticles (3-C(12)MPGN) via an interfacial 1,3-dipolar cycloaddition. At atmospheric pressures, the reaction proceeds slowly (if at all) and makes this reaction impractical for the synthetic modification of the nanoparticles. However, by performing the reaction under the high-pressure conditions, the reaction proceeds efficiently and quantitatively. TEM shows that the use of high pressure does not affect the size of the gold nanoparticle core. The 3-C(12)MPGNs were characterized by (1)H NMR spectroscopy by comparing the spectra obtained with those of model reactions utilizing N-dodecylmaleimide (4) with the same nitrones (a-i) to form 5. Additionally, the cycloaddition reaction also occurs more readily with 4 than with 2-C(12)MPGN with all nitrones, indicating that the environment of the latter affects the cycloaddition reaction.

Water‐Soluble Maleimide‐Modified Gold Nanoparticles (AuNPs) as a Platform for Cycloaddition Reactions

“…We can take advantage of organic solvent solubility of these nanoparticles to avoid hydrolysis by carrying out all the interfacial reactions in polar organic media. The yields of all transformations are very high, and the reaction time is shorter than that of organic soluble maleimide/dodacane thiol‐AuNPs previously reported 19,20. All the AuNPs and cycloadducts remain soluble in water and a host of organic solvents.…”

“…In 2006, we reported the functionalization of AuNPs with thiols bearing maleimide moieties 17. The reactivity of these organic solvent‐soluble maleimide/dodecane thiol‐AuNPs was subsequently examined towards the Michael addition reaction,18 the 1,3‐dipolar cycloaddition,19 and the Diels–Alder cycloaddition 20. Although this contribution was an important step forward for their use as a template for building new architectures, it was limited to the use of a narrow range of organic solvents for further modification of AuNPs, while requiring long reaction times.…”

Reversible Nanogate System for Mesoporous Silica Nanoparticles Based on Diels–Alder Adducts

“…In particular, AuNPs have been widely used in other biomedical disciplines, such as nanotherapeutics and gene monitoring/modulation devices for living cells . Additionally, gold shows great compatibility with the chosen thermosensitive moiety, which has been employed by Workentin and co‐workers in studies on cycloadditions onto AuNPs and the development of AuNPs‐based assemblies and platforms throughout this type of reaction …”

High diastereoselectivity induced by intermolecular hydrogen bonding in [3 + 2] cycloaddition reaction: experimental and computational mechanistic approaches

“…Cycloaddition reactions between acyclic/cyclic nitrones (azomethine‐ N ‐oxides) and N ‐aryl substituted maleimides have been studied extensively in the last 2 decades . As is well known aldonitrones may have 2 configurations that may interconvert.…”