A small heterobifunctional ligand provides stable and water dispersible core–shell CdSe/ZnS quantum dots (QDs)

Abstract

We describe a simple method to prepare water dispersible core-shell CdSe/ZnS quantum dots (QDs) 1 by capping QDs with a new thiol-containing heterobifunctional dicarboxylic ligand 4 (DHLA-EDADA). This ligand, obtained on a gram scale through a few synthetic steps, provides a compact layer on the QDs, whose hydrodynamic size in H2O is 15 nm ± 3 nm. The colloidal stability is dramatically enhanced with respect to the well-known (±) α-lipoic acid (DHLA). The ligand affinity towards QDs and the water dispersibility of nanocrystals 1 are addressed by the dithiol groups of DHLA, which chelate the zinc of the shell, and by the dicarboxylic groups of the ethylenediamine-N,N-diacetic acid (EDADA) residue, respectively. The effects of pH, buffer solutions, and biological medium on the stability of QDs 1 were assessed by monitoring the photoluminescence (PL) and hydrodynamic size over time. Highly fluorescent QD dispersions, stable over extended periods of time and over broad pH ranges and buffer types, were obtained. Furthermore, we show that the DHLA-EDADA ligand 4 also endows QDs with functional groups suitable for further conjugation and for metal ion detection. As a case study to illustrate the potential of our approach, we report the preparation and characterization of a highly luminescent orange light emitting polymer-QD 1 composite film.

Glyco-Coated CdSe/ZnS Quantum Dots as Nanoprobes for Carbonic Anhydrase IX Imaging in Cancer Cells

“…They were prepared by following a synthetic strategy that includes a key copper(I)-catalyzed azide-alkyne cycloaddition reaction (CuAAC) between the terminal alkyne residues of the DHLA-EDADA derivative 4 and the terminal azide residues of the sulfonamide derivative 5 ( Scheme 1 A) and the acetylated β-O-glucoside 6 , 29 respectively ( Scheme 1 B). The bifunctional di-alkyne derivative 4 was easily prepared in high yield (75% yield) by 2-(1 H -benzotriazole-1-yl)-1,1,3,3-tetramethylaminium tetrafluoroborate (TBTU) mediated coupling of DHLA-EDADA 7 ( 25 ) with the commercially available propargylamine 8 ( Scheme 1 B). In turn, the synthesis of 5 ( Scheme 1 A) was performed by the acylation chemistry of the PEGylated amine 9 ( 30 ) with the commercially available Meldrum’s acid 10 in mild conditions (40 °C, 18 h, DCM, 96% yield).…”

“…As shown in Figure 3 B, confocal microscopy imaging revealed a specific recognition of membrane CA IX by CAI-Glc-QDs 1 as early as after 1 h of incubation at the concentration of 200 μg/mL, with no relevant signals at lower concentrations ( Figure S8B and F , Supporting Information). Then, as proof of the CAI-mediated specific labeling of the membrane, DHLA-EDADA-coated CdSe/ZnS QDs 15 ( 25 ) ( Figures S9 and S10 , Supporting Information) were used as control. No signal was detected, confirming the specificity of our probe ( Figures 3 C and S8 ).…”

“…The glucose residues of 13 were deacetylated under basic conditions (K 2 CO 3 , MeOH, 24 h, 57% yield) affording the divalent Glc-bearing ligand 3 . Trioctylphosphine oxide (TOPO)-coated CdSe/ZnS nanocrystals 14 (Figure A and Scheme S2, Supporting Information) were prepared, as previously reported . Then, nanoprobe 1 (Figure A) was prepared by exploiting the well-known surface exchange reaction on the TOPO-coated CdSe/ZnS QDs 14 and using a mixture of thiolate ligands 2 and 3 .…”

“…In this framework, we have recently demonstrated that a small heterobifunctional ligand named DHLA-EDADA , was able to provide highly fluorescent CdSe/ZnS QD suspensions that showed remarkable colloidal stability. Indeed, DHLA-EDADA coated QDs were stable over extended periods of time and over a wide pH range and with different buffer types ( i.e .…”

“…PBS, TRIS, DMEM). The DHLA-EDADA ligand (Figure ) consisted of a dihydrolipoic acid (DHLA) residue, which provides thiol groups with high affinity for the ZnS shell, which is conjugated to the terminal amine group of an ethylenediamine- N , N -diacetic acid residue (EDADA), which, in turn, provides two-terminal carboxylic groups suitable for further conjugations …”