Hydrogen Bond-Enhanced Nanoaggregation and Antisolvatochromic Fluorescence for Protein-Recognition by Si-Coumarins

Abstract

Silicon-substituted coumarin (SiC) was established as a substantial family of both intramolecular and intermolecular hydrogen bond (H-bond) enhanced fluorescent probes for sensitively tracking proteins in vivo through the assemble and disassemble of its nanoaggregates. The intramolecular H-bond in SiC has led to significant aggregation, antisolvatochromism, and strong fluorescence with bathochromically shifted spectra into farred or near-infrared (NIR) regions in polar, protic environments. Without further furnishing with organic linkers, the compact skeleton of SiC bearing H-bond has ensured sensitively and selectively sensing the targeting proteins with the protic reaction pockets through efficient disassemble of the aggregates. In the existence of strong intermolecular H-bonds with the target protein pocket, SiC resolved as high as >250-fold fluorescence enhancement. Selectively tracking proteins, including human serum albumin, human carbonic anhydrase (hCAII), avidin, SNAP-tag protein, and translocator protein, has confirmed SiC a versatile skeleton for sensitively monitoring proteins in complicated biological systems.

Enhanced Fluorescence by Inter/Intramolecular Hydrogen Bonding in Si-Substituted Coumarins

“…In addition to intermolecular H-bonds, intramolecular H-bonds also offer distinct photophysical properties in Si-coumarins . We have recently demonstrated that intramolecular H-bonds can form between the hydrogen atom of the amide linkage and ketone oxygen in the analogue of SiC-BZA, SiC-BZA1 .…”

“…Inspired by SiXs, we have recently developed a series of silicon-substituted coumarins (Si-coumarins). − The incorporation of silicon atoms into the coumarin skeleton has resulted in an extensive collection of fluorophores with unique photophysical properties. Except for the bathochromic shift of spectra by replacing the oxygen atom with a silicon atom, as observed in most of the silicon-substituted fluorophores, Si-coumarins have demonstrated ultrahigh sensitivity to the polarity and proticity of microenvironments .…”

“…Except for the bathochromic shift of spectra by replacing the oxygen atom with a silicon atom, as observed in most of the silicon-substituted fluorophores, Si-coumarins have demonstrated ultrahigh sensitivity to the polarity and proticity of microenvironments . Uniquely, Si-coumarins have profoundly increased fluorescence quantum yield in protic solvents . Compared to oxygen-coumarin, the larger atomic radius (Si vs O: 111 vs 66 pm), longer C–Si bond length (C–Si vs C–O: ∼1.91 vs ∼1.37 Å), and specific interactions (σ*−π* conjugation) between the Si atom and the conjugated π system may impact the photophysical properties of Si-coumarin in depth.…”

“…As reported in silole, the silicon bridge in the coumarin skeleton also changes the electronic structure through orbital interactions. − However, the extraordinary impact of heteroatoms in the coumarin skeleton and associated mechanisms are rarely explored. Our previous studies showed that the fluorescence spectra and lifetime of Si-coumarins are largely solvent-dependent . Moreover, the fluorescence of Si-coumarins is significantly enhanced in hydrogen bond-donating solvents, which is poorly understood.…”

“…23−25 studies showed that the fluorescence spectra and lifetime of Sicoumarins are largely solvent-dependent. 21 Moreover, the fluorescence of Si-coumarins is significantly enhanced in hydrogen bond-donating solvents, which is poorly understood.…”