Supramolecular systems for bioapplications:recent research progress in China

Supramolecular systems feature dynamic,reversible and stimuli-responsive characteristics,which are not easily achieved by molecular entities.The last decade has witnessed tremendous advances in the investigations of supramolecular systems for various bioapplications,which include drug delivery,anticancer therapy,antibacterial therapy,photodynamic therapy,photothermal therapy,combination therapy,antidotes for residual drugs or toxins,and bioimaging and biosensing.Host-guest chemistry has played a key role in the development of such bioactive supramolecular systems,and natural macrocycles(such as cyclodextrins),synthetic macrocycles(such as calixarenes,cucurbit[n]urils,and pillararenes),and porous framework polymers(such as supramolecular organic frameworks and flexible organic frameworks)have been most successfully used as hosts to build different kinds of host-guest systems for attaining designed biofunctions.The self-assembly of rationally designed amphiphilic molecules,macromolecules and polymers represent another important approach for the construction of supramolecular architectures with advanced biofunctions.In this review,we summarize the important contributions made by Chinese researchers in this field,with emphasis on those reported in the past five years.

Fluorescent probes for detection of biothiols based on “aromatic nucleophilic substitution-rearrangement” mechanism

Biothiols,including cysteine(Cys),homocysteine(Hey),and glutathione(GSH) play important roles in physiological processes,and the detection of thiol using fluorescent probes has attracted attention due to their high sensitivity and selectively and invasive on-time imaging.However,the similar structures and reactivity of these biothiols present great challenges for selective detection.This review focused on the the "aromatic nucleophilic substitution-rearrangement(SNAr-rearrangement) mechanism",which provided a powerful tool to design fluorescent probes for the discrimination between biothiols.We classify the fluorescent probes according to types of fluorophores,such as difluoroboron dipyrromethene(BODIPY),nitrobenzoxadiazole(NBD),cyanine,pyronin,naphthalimide,coumarin,and so on.We hope this review will inspire exploration of new fluorescent probes for biothiols and other relevant analytes.

Cascade reaction-based fluorescent probe for detection of H2S with the assistance of CTAB micelles

We report a turn-on fluorescent probe for H2S through a cascade reaction using a new trap group 4- （bromomethyl）benzoate, based on excited-state intramolecular proton transfer （ESIPT） sensing mechanism. The probe showed good selectivity and high sensitivity towards H2S and it was capable of detecting and imaging H2S in living HeLa cells, indicating its potential biological applications.

Visualizing nitric oxide-dependent HIF-1 activity under hypoxia with a lipid droplet-targeting fluorescent probe

Evaluating the correlation between hypoxia inducible factor 1(HIF-1) and nitric oxide(NO) generated under hypoxia is of great significance. In this work, we developed a fluorescent probe for the monitor of HIF-1 activity influenced by NO under hypoxia in hepatoma cells with dual-targeting for hepatocyte and lipid droplet(LD). The probe shows excellent selectivity to NO and high sensitivity with 6000-fold fluorescence enhancement. Live cell imaging experiments revealed the probe’s capability of imaging exogenous and endogenous NO with specific in LDs of Hep G2 cells. For cells under hypoxia, HIF-1 induced LD level is observed to correlate with NO level. This work provides the in-situ visualization of NO-dependent HIF-1 upregulation through LD accumulation.

Monofunctionalized pillar [5] arene-based stable [1] pseudorotaxane

We reported a new monofunctionalized pillar[5]arene bearing imidazolium moiety that formed stable [1]pseudorotaxane even at high concentration （100 mmol/L） in chloroform. The self-assembly was detailed investigated by multiple methods, including varying concentration 1H NMR, 2D COSY NMR, 2D NOESY NMR, viscosity measurements, 2D DOSY NMR, and HR-ESI-MS analysis. [llRotaxane was obtained efficiently through photo thiol-ene reaction which further confirmed the formation of [l]pseudorotaxane.

Organic Composite Crystal with Persistent Room-Temperature Luminescence Above 650 nm by Combining Triplet–Triplet Energy Transfer with Thermally Activated Delayed Fluorescence

Structural modifications are a successful and commonly used approach to tune the emission properties of diverse fluorophores,but extending this approach to heavy-atom-free persistent luminophores has so far been unsuccessful.Here we employed a novel strategy to demonstrate triplet–triplet energy transfer from an organic room-temperature phosphor(RTP)with persistent luminescence to an organic molecule with thermally activated delayed fluorescence(TADF).We illustrated this approach by preparing heavy-atom-free composite crystals of an RTP with a long-lifetime emission and a red emissive organic fluorophore with TADF to yield materials with emission above 650 nm.The emission arose from the triplet excited state of an acceptor undergoing thermally activated reverse intersystem crossing(RISC)to the emissive S1 state.Such composite crystal is the first organic material with persistent TADF,achieved by triplet–triplet energy transfer.

A BODIPY analogue from the tautomerization of sodium 3-oxide BODIPY

The introduction of hydroxy group to the 3- or 5-position of 4,4-difluoro-4-bora-3aAa-diazaindacene （BODIPY） results in unexpected tautomerization to BDPONa with interesting structural and photophysical properties. The core of BDPONa is an anion with sodium cation as counter-ion. BDPONa displays strong fluorescence in organic solvents.

Difluoroboron β-diketonate dye with intense red/near-infrared fluorescence in solutions and solid states

Difluoroboronβ-diketonate(BF2bdk)complexes have attracted much attention due to their outstanding photophysical properties.However,BF2bdk with near-infrared fluorescence usually suffer from emission quenching in solid state due to theπ-πstacking in aggregation.Herein,we report a BF2bdk dye exhibiting donor-acceptor(D-A)structure with the difluoroboron moiety acting as the electron acceptor and the aminonaphthalene as the electron donor.It processes intense molar extinction coefficient,large Stokes shift and strong fluorescence in red/NIR region in both solution and aggregations.It was used for NIR imaging in living cells.

Aggregation Turns BODIPY Fluorophores into Photosensitizers:Reversibly Switching Intersystem Crossing On and Off for Smart Photodynamic Therapy

We report for the first time a practical and simple supramolecular approach to turn fluorophores into photosensitizers(PSs).Using boron dipyrromethene(BODIPY)as a proof-of-concept,eight BODIPY derivatives manifest bright fluorescence and generate negligible singlet oxygen in solution.In contrast,aggregation fails to emit fluorescence and enhances singlet oxygen generation.Experimentally,these aggregates have excellent photodynamic therapy(PDT)performance,and one even exhibits much stronger photocytotoxicity than the commercialized PS Ce6 under identical conditions.Theoretical studies show that this property originated from significantly reduced energy gaps between relevant excited singlet and triplet states,leading to considerably improved intersystem-crossing efficiency.Importantly,a simple disaggregation recovers the original properties of the fluorophores.This reversible switching property between fluorophores and PSs assists the development of smart PDT systems,in which singlet oxygen generation in tumors can be controlled in an intelligent manner after PDT treatment.The present work provides a novel strategy to design heavy-atom-free PSs and may pave the way to the development of smart PDT systems.