Cytotoxic gold(i)-bearing dendrimers from alkyne precursors

Abstract

A series of four dendrimers end-functionalized with gold(I) has been prepared from alkyne-terminated precursors and (tricyclohexylphosphine)gold(I) azide. Isolated yields range from 84-89%, based on gold. The first-generation dendrimer is cytotoxic toward 3T3 mouse fibroblast cells. Apoptosis ensues within 6 h of treatment with gold(I).

Au-iClick mirrors the mechanism of copper catalyzed azide–alkyne cycloaddition (CuAAC)

“…[2][3][4] Others [5][6][7] extended iClick to include the already prevalent [8][9] cycloaddition of an organic substrate to either a metal-azide or metal-acetylide. 7,[10][11][12][13][14][15][16][17][18][19][20][21] Important to this work, Gray et al 22 demonstrated that gold-acetylides and gold-azides will undergo cycloaddition to their organic counterparts. Despite the fact that several transition metals other than Cu(I) catalyze the azide-alkyne cycloaddition, including ruthenium, silver, and iridium, [23][24][25][26] it became apparent that not all metal-acetylide/azide species will participate in the iClick cycloaddition.…”

Organogold oligomers: exploiting iClick and aurophilic cluster formation to prepare solution stable Au4 repeating units

“…6 Critical in the pursuit of building complexity is the precise control of bond forming events and is particularly exemplified by the Cu I catalyzed azide-alkyne cycloaddition reaction (CuAAC). Others [11][12][13] have broadened the iClick concept to include the cycloaddition of organic substrates to either a metal-azide or metal-acetylide (M; Scheme 1), which are already rather prevalent reactions, [13][14][15][16][17][18][19][20][21][22][23][24][25] and the subject of reviews. The metal-azide/metal-acetylide cycloaddition (M-M′) was given the term inorganic click (iClick) as a distinguishing feature that calls attention to chemistry occurring within the coordination sphere of a metal ion.…”

Azide Chemistry – An Inorganic Perspective, Part II[‡][3+2]‐Cycloaddition Reactions of Metal Azides and Related Systems

“…[447,449] Gold-peptide bioconjugates overcome cisplatin resistance in a cancer cell line. [449] An allylpalladium azide which undergoes 1,3-dipolar cycloaddition with alkynes is proposed as key intermediate in the www.zaac.wiley-vch.de [458] three component-coupling reaction of activated alkynes, allyl-methyl carbonate and trimethylsilyl azide for the regiospecific synthesis of 2-allyl-1,2,3-triazoles.…”

“…[427] Recently, a series of interesting gold complexes with carbon-bound triazolate ligands has been obtained by Gray and by Metzler-Nolte and co-workers from reactions of phosphinegold(I) azides with terminal organic alkynes (Equation (13)). [446][447][448][449] In the place of phosphine ligands, also N-heterocyclic carbenes have been used, and a series of functionalized alkynes has been introduced in these reactions. [448] Until now the mechanism of formation of the C-bound triazolate has not been established.…”

“…[77] Exceptions are the azide ligands in Cp(Ph 2 PCH 2 CH 2 PPh 2 )RuN 3 (82) as well as in R 3 PAuN 3 and (carbene)AuN 3 which add terminal alkynes to afford triazolato complexes (see below). [178,[446][447][448] Kinetic studied were performed on the reactions of MeO 2 C-CϵC-CO 2 Me with L(chelate)CoN 3 (chelate = (DH) 2 , (acac) 2 ) (81), [184,441,442] and of azidonickel(II) complexes with monoanionic, tridentate N,N,S ligands (85a). [85] The activation parameters ΔH and ΔS for the reaction of the Co and Ni complexes are similar to those found for the reaction of phenyl azide with DMAD.…”