This line of research focuses on the development of dual macrocyclic rotaxanes, offering unique sensing opportunities in complex biofluids like blood serum where traditional supramolecular systems have faced challenges in sensitivity and selectivity. Utilizing the macrocycle cucurbit[8]uril, we capitalize on its capacity to incorporate two molecules within its cavity, promoting close interaction between a reporter dye and a target analyte (e.g., aromatic amino acids like Trp and Phe). This molecular proximity facilitates electronic coupling, yielding sensitive readouts such as emission changes. Furthermore, the bulky stopper groups prevent the disassembly of CB8-dye rotaxanes in saline media, such as biofluids, which is essential for their use in real sensing applications.

Nat. Commun. 2023, 14, 518; link.

We have pioneered the development of Zeolite-based Artificial Receptors (ZARs), a novel class of hybrid nanosensors self-assembled from inorganic porous zeolite nanoparticles and organic cofactors, such as dicationic dyes. Our first generation of ZARs demonstrates the ability to reversibly bind neurotransmitters like serotonin and dopamine with unparalleled affinity and selectivity in biofluids, rivaling the performance of natural protein receptors. These chemosensors harness the non-classical hydrophobic effect and direct non-covalent recognition motifs to generate unique binding pockets within the micropores, effectively emulating the specific protein binding pockets for the desired analyte. The tunability of the inorganic material framework and the organic dye offers a virtually limitless array of possibilities for detecting small biorelevant molecules.

Adv. Mater. 2021, 2104614, (front cover); link.

Our group is developing innovative chemiluminescent chemosensors for the fluorescence background-free detection of bioanalytes and metabolites in biofluids. Unlike conventional fluorescence-based chemosensors, our chemiluminescent chemosensors, composed of cucurbit[n]uril (CBn) and dioxetanes, generate luminescence without the need for external light sources, utilizing the chemical energy stored in the "chemiluminescent fuel." This approach enhances the signal-to-noise ratio and enables detection of drugs in turbid media. Our chemosensor design is founded on the observation that dioxetanes' chemiluminescence is amplified when forming an inclusion complex with CBn, but significantly decreases when displaced from the macrocycle cavity by the analyte. Consequently, the CBn macrocycle serves as both a receptor and a non-surfactant chemiluminescence performance enhancer, which can also be applied to commercial dioxetane-based reagents.

ACS Sens. 2022, 7, 231; link.

Our group is investigating non-covalent ensembles of chiral analytes and chromophoric hosts/receptors to characterize the chiroptical fingerprints that emerge in the corresponding Electronic Circular Dichroism (ECD) and Fluorescence-Detected Circular Dichroism (FDCD) spectra. These chiroptical signals allow for the distinction between even structurally closely related analytes that are indistinguishable by absorbance or emission spectroscopy. Furthermore, label-free reaction monitoring of processes such as enzymatic reactions, racemization, and sensing in biofluids can be achieved using ECD or FDCD in conjunction with suitable chemosensors.

Chem. Sci. 2021, 12, 9420; link. Chem. Commun. 2020, 56, 4652, link.
Angew. Chem. Int. Ed. 2014, 53, 5694; link.

One line of research in the group focuses on deciphering the driving forces behind supramolecular chemistry, particularly in water, which is vital for understanding binding mechanisms. Traditional approaches emphasize direct interactions between solutes, such as host and guest molecules. However, we explore an alternative, more potent strategy that seeks to maximize binding strength by releasing high-energy cavity water molecules from hydrophobic, enclosed spaces during receptor-ligand or host-guest binding in water. This non-classical hydrophobic binding signature can also be examined from the perspective of differential cavitation energy, providing valuable insights into supramolecular interactions. 

Chem. Eur. J. 2022, 28, e202200529; link. Chem: Eur. J., 2020 , 26, 7433; link.
Chem. Commun. 2019, 55, 14131; link. Nat. Chem. 2018, 10, 1252; link.
Chem. Rev. 2016, 116, 5216; link. Angew. Chem. Int. Ed. 2014, 53, 11158; link.
JACS, 2013, 135, 14879; link. JACS, 2012, 134, 15318; link.

This line of research is focused on developing innovative kinetic and thermodynamic assays that provide significant benefits compared to traditional indicator displacement assays (IDA). By simply reversing the assay sequence, we can accurately determine the binding affinity of insoluble or weakly binding analytes using an analyte/guest displacement assay (ADA or GDA). Additionally, time-resolved assays allow for easy measurement of kinetic binding and unbinding parameters for non-chromophoric analytes. These novel assay types open up new possibilities for sensing applications in complex media, even when only unselectively binding receptors are available.

Chem. Commun. 2022, 58, 13947; link. Chem. Commun. 2021, 57, 12663; link. 
ACS Appl. Nano Mater. 2021, 4, 4676; link. Chem. Sci. 2021, 12, 865; link. 
Chem. Commun. 2020, 56, 12327;  link. Chem. Commun. 2020, 56, 6620; link.
Chem. Sci. 2019, 10, 6584; link.

Fueled by curiosity, our team investigates the unique photophysical characteristics of unconventional dyes. For instance, we have discovered the smallest green-emitting dye to date, HINA, which comprises a mere 14 atoms. Additionally, we have developed a fluorescent paracyclophane-based indicator dye for the macrocycle cucurbit[8]uril, demonstrating an exceptionally high binding affinity (log K_a > 12) for this host in water." 

Chem. Sci. 2021, 12, 1392-1397, link, Wikipedia, Chemistry World; 
Chem. Sci. 2019, 10, 6584 (Hot Article Collection + Chem Pick of the Week); link.