Tuning the Surface Chemistry of Second-Harmonic-Active Lithium Niobate Nanoprobes Using a Silanol–Alcohol Condensation Reaction

Abstract

The surface functionalization of nanoparticles (NPs) is of great interest for improving the use of NPs in, for example, therapeutic and diagnostic applications. The conjugation of specific molecules with NPs through the formation of covalent linkages is often sought to provide a high degree of colloidal stability and biocompatibility, as well as to provide functional groups for further surface modification. NPs of lithium niobate (LiNbO3) have been explored for use in second–harmonic-generation (SHG)-based bioimaging, expanding the applications of SHG-based microscopy techniques. The efficient use of SHG-active LiNbO3 NPs as probes will, however, require the functionalization of their surfaces with molecular reagents such as polyethylene glycol and fluorescent molecules to enhance their colloidal and chemical stability and to enable a correlative imaging platform. Herein, we demonstrate the surface functionalization of LiNbO3 NPs through the covalent attachment of alcohol-based reagents through a silanol–alcohol condensation reaction. Alcohol-based reagents are widely available and can have a range of terminal functional groups such as carboxylic acids, amines, and aldehydes. Attaching these molecules to NPs through the silanol–alcohol condensation reaction could diversify the reagents available to modify NPs, but this reaction pathway must first be established as a viable route to modifying NPs. This study focuses on the attachment of a linear alcohol functionalized with carboxylic acid and its use as a reactive group to further tune the surface chemistry of LiNbO3 NPs. These carboxylic acid groups were reacted to covalently attach other molecules to the NPs using copper-free click chemistry. This derivatization of the NPs provided a means to covalently attach polyethylene glycols and fluorescent probes to the NPs, reducing NP aggregation and enabling multimodal tracking of SHG nanoprobes, respectively. This extension of the silanol–alcohol condensation reaction to functionalize the surfaces of LiNbO3 NPs can be extended to other types of nanoprobes for use in bioimaging, biosensing, and photodynamic therapies.

Revisiting carboxylic group functionalization of silica sol–gel materials

“…Based on the nucleophilicity of the Si-O À group, Gates' lab has tackled a very interesting approach for introducing carboxylic acid functions on silica surfaces based on the alcoholysis of a bifunctional alcohol-acid with a long hydrocarbon chain such as 12-hydroxydodecanoic acid (12-HDA) in propylene carbonate, a green solvent (Scheme 6). 84,102 This chemistry relies on the formation of a Si-O-C bond, in other words a silicic ester, having been studied more than 50 years ago. 103,104 The activation energy for the esterification reaction is 91.6 kJ mol À1 for inserting butoxy groups while for the hydrolysis it is 37.0 kJ mol À1 .…”

“…109,110 In this context, anchoring 12-HDA to the SiO 2 surface allowed further condensing chemistries on the -COOH groups, for example, an amine fluorescent probe and a maleimide-PEG-amine (Scheme 7). 102 Recently, Barczak claimed that the SiO À nucleophile from surface silanols can attack the carbonyl atoms of 2,2-dimethyl-1,3-dioxane-4,6-dione (Meldrum's acid) inducing a ring opening process to form an anchored malonic acid ester, as depicted in Scheme 8. 111 FTIR shows absorption at 1720 cm À1 from the carbonyl stretching modes n CQO .…”

“…(Reproduced with permission from American Chemical Society. 102 Copyright 2021 American Chemical Society).…”

“…109,110 In this context, anchoring 12-HDA to the SiO 2 surface allowed further condensing chemistries on the –COOH groups, for example, an amine fluorescent probe and a maleimide-PEG-amine (Scheme 7). 102…”

Solution‐Based Synthesis Routes for the Preparation of Noncentrosymmetric 0‐D Oxide Nanocrystals with Perovskite and Nonperovskite Structures

“…The above kinetic aspects and growth mechanisms, when reported in the literature, are indicated in the next sections of this review only dedicated to 0-D dielectric nanomaterials and whose global outline is largely inspired from the excellent contributions of Charles et al [56] and Schnepp et al [57] Very notably, the overall complexity of NCO nanocrystals has recently been increased in terms of chemical compositions with the synthesis of three-and four-cation perovskites belonging to high-symmetry point groups, [8,58] in terms of new functional optical properties with the doping by fluorescent rare-earth ions, [59][60][61] in terms of crystalline structures with new hosts belonging to low-symmetry point groups [62,63] and finally, in terms of surface functionalization for bioimaging [64,65] and for the two-photon-triggered photorelease of caged compounds in advanced drug-delivery theranostic applications. [66,67] In parallel, the experimental techniques (TEM imaging, synchrotron radiations, pair distribution function analysis of the Bragg and diffuse scattering components, SAXS, real-time UV-Vis, FTIR, DLS, SHG, and AFM-based experiments, etc.)…”