Competitive Anionic Exchange of Thiolate Ligands onto Aqueous Phosphonate-Capped Quantum Dots

Abstract

This study examines the relative binding strength of a series of thiolate ligands to the surfaces of zincblende CdSe/ZnS core/shell quantum dots (QDs) passivated by phosphonate ligands under basic conditions in water by means of isothermal titration calorimetry (ITC). A labile hydrophilic intermediate, 2aminoethylphosphonic acid (AEP), was introduced in place of native hydrophobic carboxylate ligands to produce water-soluble QDs and provide a universal starting point for competitive anionic exchange reactions. We introduce monothiols of different chain lengths, and a dithiol analogue (dihydrolipoic acid), to probe the effects of chain length and denticity on binding strength. The introduction of each of the ligands produces an exothermic response. An increase in chain length among the monothiols led to an increase in the equilibrium exchange constant, K ex , indicating longer chain lengths lead to stronger binding. However, the shorter chain mercaptopropionic acid showed greater total exothermicity, which appears to indicate a greater total number of accessible binding sites. The introduction of a dithiol ligand produces a larger K ex than the monodentate thiols, consistent with greater binding strength and stability inferred from previous observations, and ligand density comparable to the shorter chain mercaptopropionic acid at saturation. This work should aid in the development of stable and versatile water-soluble QD colloids for bioimaging and sensing applications.

Thermodynamics of nanocrystal–ligand binding through isothermal titration calorimetry

“…However, saturating conditions can be useful in providing colloidal stability when using a weakly associating initial ligand L 1 as a “leaving group” for installation of several stronger binders L 2 , for which K ex and Δ H can be compared from parallel titrations. 56…”

“…For thermodynamic studies of ligand coordination in buffered aqueous solution, an initial exchange with a ligand that supports colloidal stability in water, and yet is labile toward exchange with more strongly binding ligands of interest, may be advantageous. 56,160,161 Control of pH and ionic strength is critical, as these will modulate the protonation state of binding motifs and solution phase ligands, and influence charge balance considerations.…”

“…However, saturating conditions can be useful in providing colloidal stability when using a weakly associating initial ligand L 1 as a ''leaving group'' for installation of several stronger binders L 2 , for which K ex and DH can be compared from parallel titrations. 56 The more common case for NC ligand exchange is that the sites are nearly filled with the initial ligand L 1 , but the concentration of L 1 in solution is low, such that [L 1 ] t is approximated by the total concentration of sites ([L 1 ] t E N[M] t ). This is typically the case for quantum dots with anionic organic ligands following initial purification in nonpolar solvents, for example.…”

“…Several groups have turned to ITC in recent years as a means to study NC surface chemistry. 51,[55][56][57][58][59][60][61][62][63][64][65][66] It is able to detect ligand binding at a wide range of NC concentrations, which enables measurement of different binding constant ranges, and it is not limited to studying processes with distinctive NMR, UV-visible, or IR spectroscopic signatures. 55,[67][68][69] A key feature of ITC is the ability to resolve sites with different binding constants based on different enthalpies of binding.…”

Impact of Uniform Facets on the Thermodynamics of Ligand Exchanges on Colloidal Quantum Dots

“…Isothermal titration calorimetry has been used to directly measure the thermodynamics of inter-ligand interactions on quantum dots ,,,− and is the best technique to tease out these effects considering its sensitivity. Further, we have shown that both 1 H NMR and isothermal titration calorimetry data are needed to capture the complexity of the interactions between ligands using a composition-dependent model to obtain consistent thermodynamic parameters. , Critically, by performing ligand exchanges on nanocrystals that are identical in every way except their terminating facets, the effect of nanocrystal facets on ligand exchanges can be measured and quantified.…”