Remarkable high-yielding chemical modification of gold nanoparticles using uncatalyzed click-type 1,3-dipolar cycloaddition chemistry and hyperbaric conditions Hossein Ismaili, Abdolhamid Alizadeh, Kristen E. Snell, and Mark S. Workentin Abstract: Azide-terminated alkyl thiolate monolayer-protected gold nanoparticles (1-C12MPN) with a core size of 1.8 ± 0.2 nm were prepared. 1-C12MPN was modified in high yields via an uncatalyzed 1,3-dipolar cycloaddition (click- type reaction) with a variety of terminal acyl–alkynes under hyperbaric conditions at 11 000 atm. The resulting 1,2,3-tria- zole modified MPNs (2-C12MPN) were characterized using 1 H NMR spectroscopy and were verified by comparison of the spectra to those obtained for the products of the model reactions of 1-azidododecane with the same alkynes. TEM analysis showed that the high-pressure conditions did not affect the size of the gold core, suggesting that the only effect is to facili- tate the chemical reaction on the particles. Key words: nanoparticles, hyperbaric chemistry, 1,3-dipolar cycloaddition, monolayers. Re ´sume ´: On a pre ´pare ´ des nanoparticules d’or prote ´ge ´es par une monocouche d’alkylthiol (1-C 12 MPN) portant une fonc- tion azide en position terminale et dont le diame `tre principal est e ´gal a ` 1,8 ± 0,2 nm. Le produit 1-C 12 MPN a e ´te ´ modifie ´ avec des rendements e ´leve ´s par le biais d’une cycloaddition 1,3-dipolaire non catalyse ´e (re ´action de type par un clic) avec une varie ´te ´ d’acyl–alcynes terminales, dans des conditions hyperbariques, a ` 11,000 atmosphe `res. Les nanoparticules d’or modifie ´es, prote ´ge ´es par une monocouche d’alkylthiol (2-C 12 MPN) et portant un cycle 1,2,3-triazole ont e ´te ´ caracte ´rise ´es par spectroscopie RMN du 1 H et ont e ´te ´ ve ´rifie ´es par comparaison avec les spectres obtenus pour les produits des re ´actions mode `les du 1-azidode ´cane avec les me ˆmes alcynes. Une analyse par microscopie e ´lectronique a ` transmission (MET) a per- mis de montrer que les conditions de haute pression n’ont pas affecte ´ la taille du diame `tre principal de l’or sugge ´rant que le seul effet est de faciliter la re ´action chimique sur les particules. Mots-cle ´s : nanoparticules, chimie hyperbarique, cycloaddition 1,3-dipolaire, monocouches. [Traduit par la Re ´daction] Introduction The Cu(I)-catalyzed Huisgen 1,3-dipolar cycloaddition of azides to terminal alkynes to produce a triazole ring, the ‘‘click’’ reaction, is a popular and powerful tool in organic synthesis and combinatorial chemistry. 1 This reaction is also being exploited in material science applications for the mod- ification of metal and silica surfaces, 2 dendrimers, 3 and poly- mers. 4 Recently, the reaction was extended to monolayer- protected CdSe, 5 iron oxide, 6 and monolayer-protected gold nanoparticles (MPN). 7–12 Because the 1,3-dipolar cycloaddi- tion reaction of an alkyne and azide is slow, this type of re- action is typically done in the presence of a Cu(I) catalyst because it facilitates the rapid, high reaction conversions with little or no byproducts under mild conditions. The later is of key importance for the functionalization of Au-MPN. While the catalyzed reaction is effective for the modification of the CdSe and iron oxide nanoparticles, this approach is not considered as feasible with gold nanoparticles. Gold MPNs (now simply referred to as MPNs) in the presence of the Cu catalyst have been suggested to be unstable, and lead to ag- gregation or decomposition likely due to the reaction of the Cu catalyst with the gold surface. In another case, Brennan et al. reported using the Cu-catalyzed route to modifiy azide- functionalized 12 nm MPNs with alkyne-appended lipases but a million-fold excess of Cu was required and the yield was less than 1% conversion. 7 More recently, and while this work was in progress, Astruc and co-workers reported spe- cific reaction conditions to circumvent the difficulties of the Cu(I) click reaction on azide-terminated MPNs. 13 Williams and co-workers reported a thorough study show- ing that the Huisgen dipolar cycloaddition reaction can be used to modify azide-terminated MPNs with a variety of ac- tivated alkynes without a catalyst. 8 However, the yields (ex- tent of conversion of the azide groups) were extremely low (13% and less after 60 h in dioxane, depending on the al- kyne) and could only be marginally improved by altering the solvent. In a latter study where they reported on the ki- netics of this reaction on the MPN, they stated that these Received 28 April 2009. Accepted 9 July 2009. Published on the NRC Research Press Web site at canjchem.nrc.ca on 21 November 2009. H. Ismaili, A. Alizadeh, 1 K.E. Snell, and M.S. Workentin. 2 Department of Chemistry, The University of Western Ontario, London, ON N6A 5B7. 1 Present address: Chemistry Department and Nanoscience and Nanotechnology Research Center (NNRC), Razi University, Kermanshah 67149, Iran. 2 Corresponding author (e-mail: mworkent@uwo.ca). 1708 Can. J. Chem. 87: 1708–1715 (2009) doi:10.1139/V09-138 Published by NRC Research Press