Controlled Click‐Assembly of Well‐Defined Hetero‐Bifunctional Cubic Silsesquioxanes and Their Application in Targeted Bioimaging

Abstract

A general procedure for the assembly of hetero‐bifunctional cubic silsesquioxanes with diverse functionality and a perfectly controlled distribution of functional groups on the inorganic framework has been developed. The method is based on a two‐step sequence of mono‐ and hepta‐functionalization through the ligand‐accelerated copper(I)‐catalyzed azide–alkyne cycloaddition of a readily available octaazido cubic silsesquioxane. The stoichiometry of the reactants and the law of binomial distribution essentially determine the selectivity of the key monofunctionalization reaction when a copper catalyst with strong donor ligands is used. The methodology has been applied to the preparation of a set of bifunctional nano‐building‐blocks with orthogonal reactivity for the controlled assembly of precisely defined hybrid nanomaterials and a fluorescent multivalent probe for application in targeted cell‐imaging. The inorganic cage provides an improved photostability to the covalently attached dye as well as a convenient framework for the 3D multivalent display of the pendant epitopes. Thus, fluorescent bioprobes based on well‐defined cubic silsesquioxanes offer interesting advantages over more conventional fully organic analogues and ill‐defined hybrid nanoparticles and promise to become powerful tools for the study of cell biology and for biomedical applications.

Stochastic/Controlled Symmetry Breaking of the T8‐POSS Cages toward Multifunctional Regioisomeric Nanobuilding Blocks

“…The clustering effect and rigid conformation lead to a very high density of functional groups per unit volume,9 which renders it an ideal counterpart to dendritic nanobuilding blocks to direct and control self‐assembly at the sub‐10 nm scale 10. To date, many applications have been explored for POSSs,8a ranging from ceramic precursors, space shuttle coating, nanolithography, and organometallic catalysts to nanomedicine,11 drug delivery, tissue engineering, and targeted bioimaging 12. Nevertheless, most known POSS compounds are either homo‐octa‐ or monofunctionalized and most of the pendant groups are inert (such as isobutyl and cyclohexyl) 13.…”

“…Hydrolytic cocondensation is thus a direct and straightforward way to prepare POSSs with mixed functional groups 16. 18 Other methods include 1) the nucleophile‐induced cage reshuffling approach,18, 19 and 2) partial functionalization of the homo‐octafunctional POSS precursor 12. 20 Statistical mixtures of multifunctional cages (and their regioisomers) are usually obtained and often difficult to separate.…”

Fluorescent‐Labeled Octasilsesquioxane Nanohybrids as Potential Materials for Latent Fingerprinting Detection

“…In this regard, polyhedralo ligomeric silsesquioxanes (POSS) have emergeda savaluableg roup of 3D nano-building-blocks for the fabrication of av ariety of hybrid functional materials. [15][16][17][18][19] Several prime qualifications make POSS the appropriate choice for its use as principal core:( i) it exhibits high stability and excellent biocompatibility in ab iological environment, [20] (ii)the inorganic cage providesn ot only protection to the covalently attached dye from stabilityb ut also ac onvenient framework for 3D multivalent display of pendant epitopes, [21] (iii)facile functionalization. [22] The highly symmetrical and topologically ideal cubic-octameric framework (T8), with general formula (RSiO1.5) 8 and ac age size of approximately 0.5-0.7 nm has been reported as suitable precursor.…”

Janus POSS Based on Mixed [2:6] Octakis‐Adduct Regioisomers

“…For highly symmetric T 8 ‐POSS, there are three regioisomers for mixed [2:6] octakis‐adducts and three for mixed [3:5] octakis‐adducts . It is usually very difficult to separate them, not to mention their selective synthesis.…”