Al igand design is proposed for transition metal nanoparticle (TMNP) catalysts in aqueous solution. Thus, at ris(triazolyl)-polyethylene glycol (tris-trz-PEG) amphiphilic ligand, 2,i su sed for the synthesis of very small TMNPs with Fe,C o, Ni, Cu, Ru, Pd, Ag, Pt, and Au. These TMNP-2 catalysts were evaluated and compared for the model 4-nitrophenol reduction, and proved to be extremely efficient. High catalytic efficiencies involving the use of only afew ppm metal of PdNPs,RuNPs,and CuNPs were also exemplified in Suzuki-Miyaura, transfer hydrogenation, and click reactions, respectively.Since the seminal discoveries by Haruta [1] and Hutchings, [2] catalysis of chemical reactions by transition metal nanoparticles (TMNPs) has attracted considerable interest owing to its efficiency, greenness,c onvenient use,a nd improved understanding of reaction mechanisms. [3][4][5][6][7][8][9] Thes upport and medium have been shown to play an essential role in TMNP catalysis,but relatively little attention has been paid to TMNP surface ligand design. Yetb oth TMNP formation in micelles or inverted micelles and catalysis therein are also strongly dependent on the stereoelectronic parameters of the stabilizing agents. [10][11][12][13] Catalysis in water offers great advantages in terms of green chemistry,a nd has recently been actively investigated. [14][15][16][17][18][19][20][21] Fori nstance,a mphiphilic dendrimers are unimolecular micelles, [18][19][20] and this property has recently been exploited for catalysis in water with little as parts per million (ppm) amounts of molecular or TMNP catalysts.[21] The synthesis and use in catalysis of amphiphilic dendrimers as nanoreactors represents avery productive sophistication, but it is time-consuming,a nd one can conceptualize ar elated approach using simpler amphiphilic ligands.Toward this goal, we suggest the design of weak, but multidentate bulky ligands that offer both easy displacement from TMNP surface by substrates for catalysis and sufficient TMNP stabilization. As ar esult, we report the amphiphilic tripodal ligand tris(1,2,3-triazolyl)-polyethylene glycol (tristrz-PEG), 2,t hat led to the synthesis of very small TMNPs with various transition metals (Fe, Co,Ni, Cu, Ru, Ag, Pt, Pd, and Au). These TMNP-2 complexes are shown to be remarkably efficient catalysts of several major green reactions.F irst, 4-nitrophenol (4-NP) reduction by NaBH 4 in water was used as am odel NP surface reaction to demonstrate the catalyst efficiencya nd compare all of these metals with one another. Then RuNP-catalyzed transfer hydrogenation of nitrobenzene with i-propanol as the hydrogen source in water/i-propanol, PdNP-catalyzed Suzuki-Miyaura crosscoupling reaction between bromobenzene and phenylboronic acid in water/EtOH, and CuNP-catalyzed azide-alkyne 1,3-cycloaddition (CuAAC, click) reaction in water were shown to work using extremely low amounts (down to afew ppm) of catalysts.Thes ynthesis of the tris-trz-PEG ligand 2 starts with the preparation of tris(1-benzyl-1H-1,2,3-triazo...