Host-guest Interactions Research Articles

Chirality Sensing of Chiral Carboxylic Acids by a Ureido-linked Zinc Bisporphyrinate.

We designed and synthesized a ureido-linked zinc bisporphyrinate [Zn2(UBis)]. CD spectra show that this zinc bisporphyrinate has the ability to sense the chirality of chiral carboxylic acids without derivatization. Our studies suggest that the phenyl ring in the linker forms π-π interactions with porphyrin planes and that the carboxylic acid is coordinated to the zinc in the host-guest complex. DFT calculations show that the bisporphyrin adopts a "Z"-shaped configuration, and that the ureido group forms hydrogen bonds with carboxylic acids. The combination ofπ-π interactions, coordination interactions and hydrogen bonding interactions leads to the chirality sensing ability of [Zn2(UBis)].

π-Conjugated Nanohoops: A new generation of curved materials for organic electronics.

Nanohoops, cyclic association of π-conjugated systems to form a hoop-shaped molecule, have been widely developed in the last 15 years. Beyond the synthetic challenge, the strong interest towards these molecules arise from their radially-oriented π-orbitals, which provide singular properties to these fascinating structures. Thanks to their particular cylindrical arrangement, this new generation of curved molecules have been already used in many applications such as host-guest complexation, biosensing, bioimaging, solid-state emission and catalysis. However, their potential in organic electronics has only started to be explored. From the first incorporation as an emitter in fluorescent Organic Light Emitting Diode (OLED), to the recent first incorporation as host in Phosphorescent OLED or as charge transporter in Organic Field-Effect Transistor (OFET) and in Organic Photovoltaics (OPV), this field has shown important breakthroughs in recent years. These finding have revealed that curved materials can play a key role in the future and can even be more efficient than their linear counterparts. This can have important repercussions for the future of electronics. Time is now come to overview the different nanohoops used to date in electronic devices in order to stimulate the future molecular designs of functional materials based on these macrocycles.

Hydrogel Nanoparticles Enable Nucleation Barrier Regulation and Ion Anchoring as an Alternative Pathway for Monosodium Urate Monohydrate Crystallization Control.

Gout flare-up, commonly resulting from monosodium urate monohydrate (MSUM) crystallization, has led to painful inflammatory arthritis among hundreds of millions of people. Herein, a kind of hydrogel nanoparticles (HNPs) with specific properties was developed, aimed at providing a promising pathway for MSUM crystallization control. The experimental and molecular dynamics simulation results synchronously indicate that the fabricated HNPs achieve efficient inhibition of MSUM crystallization governed by the mechanism of "host-guest interaction" even under very low-dose administration. HNPs as the host dispersed in the hyperuricemic model effectively lift the relative heterogeneous nucleation barrier of the MSUM crystal and hinder solute aggregation with strong electronegativity and hydrophobicity. The initial appearance of MSUM crystals was then delayed from 94 to 334 h. HNPs as the guest on the surface of the formed crystal can decelerate the growth rate by anchoring ions and occupying the active sites on the surface, and the terminal yield of the MSUM crystal declined to less than 1% of the control group. The good biocompatibility of HNPs (cell viability > 94%) renders it possible for future clinical applications. This study can guide the rational design of inhibitory nanomaterials and the development of their application in the control of relevant pathological crystallization.

Determination of Acetylamantadine by γ-Cyclodextrin-Assisted α-HL Nanopore for Potential Cancer Prediagnosis.

The high expression of Spermidine/spermine N1-acetyltransferase (SSAT-1) is an important indicator in early cancer diagnosis. Here, we developed a nanopore-based methodology with γ-cyclodextrin as an adaptor to detect and quantify acetylamantadine, the specific SSAT-1-catalyzed product from amantadine, to accordingly reflect the activity of SSAT-1. We employ γ-cyclodextrin and report that amantadine cannot cause any secondary signals in γ-cyclodextrin-assisted α-HL nanopore, while its acetylation product, acetylamantadine, does. This allows γ-cyclodextrin to practically detect acetylamantadine in the interference of excessive amantadine, superior to the previously reported β-cyclodextrin. The quantification of acetylamantadine was not interfered with even a 50-fold amantadine and displayed no interference in artificial urine sample analysis, which indicates the good feasibility of this nanopore-based methodology in painless cancer prediagnosis. In addition, the discrimination mechanism is also explored by 2-D nuclear magnetic resonance (NMR) and nanopore experiments with a series of adamantane derivatives with different hydrophilic and hydrophobic groups. We found that both the hydrophobic region matching effect and hydrophilic interactions play a synergistic effect in forming a host-guest complex to further generate the characteristic signals, which may provide insights for the subsequent design and study of drug-cyclodextrin complexes.

Topology Reconfiguration of Anion-Pillared Metal-Organic Framework from Flexibility to Rigidity for Enhanced Acetylene Separation.

Flexible metal-organic framework (MOF) adsorbents commonly encounter limitations in removing trace impurities below gate-opening threshold pressures. Topology reconfiguration can fundamentally eliminate intrinsic structural flexibility, yet remains a formidable challenge and is rarely achieved in practical applications. Herein, we present a solvent-mediated approach to regulate the flexible CuSnF6-dpds-sql (dpds = 4,4''-dipyridyldisulfide) with sql topology into rigid CuSnF6-dpds-cds with cds topology. Notably, the cds topology is unprecedented and firstly obtained in anion-pillared MOF materials. As a result, rigid CuSnF6-dpds-cds exhibits enhanced C2H2 adsorption capacity of 48.61 cm3 g-1 at 0.01bar compared to flexible CuSnF6-dpds-sql (21.06 cm3 g-1). The topology transformation also facilitates the adsorption kinetics for C2H2, exhibiting a 6.5-fold enhanced diffusion time constant (D/r2) of 1.71 × 10-3 s-1 on CuSnF6-dpds-cds than that of CuSnF6-dpds-sql (2.64 × 10-4 s-1). Multiple computational simulations reveal the structural transformations and guest-host interactions in both adsorbents. Furthermore, dynamic breakthrough experiments demonstrate that high-purity C2H4 (>99.996%) effluent with a productivity of 93.9mmol g-1 can be directly collected from C2H2/C2H4 (1/99, v/v) gas-mixture in a single CuSnF6-dpds-cds column. This article is protected by copyright. All rights reserved.

Determination of Binding Constants for the Complexes Between Heavy Metal Ions and Cucurbit[n]uril

AbstractOne of the major concerns worldwide is the rapid increase in water pollution with hazardous heavy metals. The Cucurbit[n]uril (CB[n]) structure provides an inner hydrophobic cavity accessible through two electrostatically negative portals with polar carbonyl groups, allowing for charged ion–dipole interaction between cationic species with excellent binding affinities. In this work we selected CB[5], and CB[7] for the titrimetric and electrochemical evaluation of the heavy metal complexes formed with Copper(II), Cadmium(II) and Lead(II). The host–guest interaction was found by either attenuation of the redox peaks, the formation of a new peak, or the slight shift in the redox peaks of the heavy metal ions. Titration data were obtained for CB[n] with the heavy metal solutions to determine the molar coefficient of binding. The stoichiometry of the complexes was 1 : 1 by Job′s plot. We calculated the binding constants using the Benesi–Hildebrand method achieving relatively good binding constants (K) ranging from (1.80±0.14)×105–(4.98±0.13)×105 M−1. The results showed that the complexes of Cadmium(II) and Lead(II) with both CB[5] and CB[7] are highly stable in aqueous media. Copper(II) was able to bind to the smaller sized portal of CB[5], whereas with CB[7] the heavy metal ion could not form a favourable complex. This phenomenon suggests that the CB[5] is an ideal host at forming stable host–guest interactions than their larger homologue.

Nested non-covalent interactions expand the functions of supramolecular polymer networks

Supramolecular polymer networks contain non-covalent cross-links that enable access to broadly tunable mechanical properties and stimuli-responsive behaviors; the incorporation of multiple unique non-covalent cross-links within such materials further expands their mechanical responses and functionality. To date, however, the design of such materials has been accomplished through discrete combinations of distinct interaction types in series, limiting materials design logic. Here we introduce the concept of leveraging “nested” supramolecular crosslinks, wherein two distinct types of non-covalent interactions exist in parallel, to control bulk material functions. To demonstrate this concept, we use polymer-linked Pd2L4 metal–organic cage (polyMOC) gels that form hollow metal–organic cage junctions through metal–ligand coordination and can exhibit well-defined host-guest binding within their cavity. In these “nested” supramolecular network junctions, the thermodynamics of host-guest interactions within the junctions affect the metal–ligand interactions that form those junctions, ultimately translating to substantial guest-dependent changes in bulk material properties that could not be achieved in traditional supramolecular networks with multiple interactions in series.

CO2 inside sI clathrate-like cages: Automated construction of neural network/machine learned guest-host potential and quantum spectra computations.

We present new results on the underlying guest-host interactions and spectral characterization of a CO2 molecule confined in the cages of the sI clathrate hydrate. Such types of porous solids raise computational challenges, as they are of practical interest as gas storage/capture materials. Accordingly, we have directed our efforts toward addressing their modeling in a proper manner, ensuring the quality of the input data and the efficiency of the computational approaches. The computational procedure for spectral simulations, within the multi-configurational time-dependent Hartree framework, involves the development of a fully coupled Hamiltonian, including an exact kinetic energy operator and a many-body representation of the potential, along with dipole moment surfaces, both obtained through neural network machine learning techniques. The resulting models were automatically trained and tested on extensive datasets generated by PW86PBE-XDM calculations, following the outcome of previous benchmark studies. Our simulations enable us to explore various aspects of the quantized dynamics upon confinement of CO2@D/T, such as constrained rotational-translational quantum motions and the averaged position/orientation of the CO2 guest in comparison to the experimental data available. Particularly notable are the distinct energy patterns observed in the computed spectra for the confined CO2 in the D and T cages, with a considerably high rotational-translational coupling in the CO2@T case. Leveraging reliable computations has proved instrumental, highlighting the sensitivity of the spectral features to the shape and strength of the potential interactions, with the explicit description of many-body contributions being significant.

Bulk transparent supramolecular glass enabled by host–guest molecular recognition

Supramolecular glass is a non-covalently cross-linked amorphous material that exhibits excellent optical properties and unique intrinsic structural features. Compared with artificial inorganic/organic glass, which has been extensively developed, supramolecular glass is still in the infancy stage, and itself is rarely recognized and studied thus far. Herein, we present the development of the host–guest molecular recognition motifs between methyl-β-cyclodextrin and para-hydroxybenzoic acid as the building blocks of supramolecular glass. Non-covalent polymerization resulting from the host–guest complexation and hydrogen bonding formation enables high transparency and bulk state to supramolecular glass. Various advantages, including recyclability, compatibility, and thermal processability, are associated with dynamic assembly pattern. Short-range order (host–guest complexation) and long-range disorder (three dimensional polymeric network) structures are identified simultaneously, thus demonstrating the typical structural characteristics of glass. This work provides a supramolecular strategy for constructing transparent materials from organic components.

A micro-fabricated potentiometric platform with application in a COVID-19 drug quantification and the determination of its binding affinity to a supramolecular host

Recent applications in host–guest chemistry include advanced sensing technologies, drug formulations, and drug delivery. Quantification of host–guest binding constants is significant to the continued optimization of their use. Binding constants offer valuable information about the stability and affinity of the formedcomplex that is essential to both drug formulations and delivery. In this study a novel green, portable, disposable, and cost-efficient microfabricated potentiometric sensor is introduced and successfully applied to determine the concentration of remdesivir (RMD), a COVID-19 drug, and its binding affinity to the supramolecular host sulfobutylether-β-cyclodextrin (SBEβCD) as a compatible solubilizing agent; to overcome the low water solubility of RMD which presents a significant challenge in its intravenous administration. The sensor incorporates multi-walled carbon nanotubes to improve stability and detection limits. To reduce interference effects and enhance the selectivity of the sensor for RMD, 4-tert-butyl-calix[8]arene was employed as an ionophore. A Nernstian potentiometric response for RMD over a concentration range of 1.0 × 10−3 to 1.0 × 10−6 M with a slope of 58.2 ± 0.9 mV decade−1 and a detection limit of 0.23 µM were achieved. The binding constant of the RMD-SBEβCD complex was determined to be 9.76 × 103 M−1. The proposed sensor was shown to be effective for drug quantification and measurements of binding affinities, providing valuable insights into the physicochemical properties of target drugs.

Biomimetic Hydrogen‐Bonded G ⋅ C ⋅ G ⋅ C Quadruplex within a Tetraphenylethene‐Based Octacationic Spirobicycle in Water

AbstractIn biological systems, nucleotide quadruplexes (such as G‐quadruplexes) in DNA and RNA that are held together by multiple hydrogen bonds play a crucial functional role. The biomimetic formation of these hydrogen‐bonded quadruplexes captured by artificial systems in water poses a significant challenge but can offer valuable insights into these complex functional structures. Herein, we report the formation of biomimetic hydrogen‐bonded G ⋅ C ⋅ G ⋅ C quadruplex captured by a tetraphenylethene (TPE) based octacationic spirobicycle (1). The spirobicyclic compound possesses a three‐dimensional (3D) crossing dual‐cavity structure, which enables the encapsulation of four d(GpC) dinucleotide molecules, thereby realizing 1 : 4 host–guest complexation in water. The X‐ray structure reveals that four d(GpC) molecules further form a two‐layer G ⋅ C ⋅ G ⋅ C quadruplex with Watson–Crick hydrogen bonds, which are stabilized within the dual hydrophobic cavities of 1 through the cooperative non‐covalent interactions of hydrogen bonds, CH⋅⋅⋅π interactions, and hydrophobic effect. Due to the dynamically‐rotational propeller chirality of TPE units, 1 with adaptive chirality can further serve as a chiroptical sensor to exhibit opposite Cotton effects with mirror‐image CD spectra for the pH‐dependent hydrogen‐bonded assemblies of d(GpC) including the Watson–Crick G ⋅ C ⋅ G ⋅ C (pH 9.22) and Hoogsteen G ⋅ C+ ⋅ G ⋅ C+ (pH 5.74) quartets through the host–guest chirality transfer in water.

Chirality Sensing of Cryptochiral Guests with Prism[n]arenes.

Optical chirality sensing has gained significant attention in recent years. Within this field, the quest for stereodynamic chiroptical probes capable of detecting cryptochiral guests presents a formidable challenge. Macrocycles exhibiting planar chirality have emerged as promising candidates for amplifying the chirality of cryptochiral guests. In this study, we demonstrate that the formation of host-guest complexes between cryptochiral molecules and planar chiral prismarenes triggers electronic circular dichroism (ECD) signals via host-guest complexation-induced chirality amplification. The absolute configuration of the most stable chiral macrocyclic host-guest complex has been established by resorting to both exciton model and DFT computations. Furthermore, we demonstrated that this supramolecular chirality sensing system can be employed to determine the enantiomeric composition of scalemic mixtures by measuring the ECD bands intensity. The information described here opens the way for the use of prismarenes as stereodynamic probes for sensing of cryptochiral guests.

Biomimetic Hydrogen-Bonded G ⋅ C ⋅ G ⋅ C Quadruplex within a Tetraphenylethene-Based Octacationic Spirobicycle in Water.

In biological systems, nucleotide quadruplexes (such as G-quadruplexes) in DNA and RNA that are held together by multiple hydrogen bonds play a crucial functional role. The biomimetic formation of these hydrogen-bonded quadruplexes captured by artificial systems in water poses a significant challenge but can offer valuable insights into these complex functional structures. Herein, we report the formation of biomimetic hydrogen-bonded G ⋅ C ⋅ G ⋅ C quadruplex captured by a tetraphenylethene (TPE) based octacationic spirobicycle (1). The spirobicyclic compound possesses a three-dimensional (3D) crossing dual-cavity structure, which enables the encapsulation of four d(GpC) dinucleotide molecules, thereby realizing 1 : 4 host-guest complexation in water. The X-ray structure reveals that four d(GpC) molecules further form a two-layer G ⋅ C ⋅ G ⋅ C quadruplex with Watson-Crick hydrogen bonds, which are stabilized within the dual hydrophobic cavities of 1 through the cooperative non-covalent interactions of hydrogen bonds, CH⋅⋅⋅π interactions, and hydrophobic effect. Due to the dynamically-rotational propeller chirality of TPE units, 1 with adaptive chirality can further serve as a chiroptical sensor to exhibit opposite Cotton effects with mirror-image CD spectra for the pH-dependent hydrogen-bonded assemblies of d(GpC) including the Watson-Crick G ⋅ C ⋅ G ⋅ C (pH 9.22) and Hoogsteen G ⋅ C+ ⋅ G ⋅ C+ (pH 5.74) quartets through the host-guest chirality transfer in water.

Host–Guest Interaction Study of Olmesartan Medoxomil with β-Cyclodextrin Derivatives

Olmesartan medoxomil (OLM) is a selective angiotensin II receptor antagonist used in the treatment of hypertension. Its therapeutic potential is limited by its poor water solubility, leading to poor bioavailability. Encapsulation of the drug substance by two methylated cyclodextrins, namely randomly methylated β-cyclodextrin (RM-β-CD) and heptakis(2,3,6-tri-O-methyl)-β-cyclodextrin (TM-β-CD), was carried out to overcome the limitation related to OLM solubility, which, in turn, is expected to result in an improved biopharmaceutical profile. Supramolecular entities were evaluated by means of thermoanalytical techniques (TG—thermogravimetry; DTG—derivative thermogravimetry), spectroscopic methods including powder X-ray diffractometry (PXRD), universal-attenuated total reflectance Fourier-transform infrared (UATR-FTIR) and UV spectroscopy, saturation solubility studies, and by a theoretical approach using molecular modeling. The phase solubility method reveals an AL-type diagram for both inclusion complexes, indicating a stoichiometry ratio of 1:1. The values of the apparent stability constant indicate the higher stability of the host–guest system OLM/RM-β-CD. The physicochemical properties of the binary systems are different from those of the parent compounds, emphasizing the formation of inclusion complexes between the drug and CDs when the kneading method was used. The molecular encapsulation of OLM in RM-β-CD led to an increase in drug solubility, thus the supramolecular adduct can be the subject of further research to design a new pharmaceutical formulation containing OLM, with improved bioavailability.

Water-soluble metal-organic cages crosslinked injectable hydrogel for multi-modal synergistic therapy

Despite the excessive of antibiotics causes the emergence of multidrug-resistant (MDR) bacteria, antibiotic therapy remains the most effective and fastest-acting strategy currently available. Water-soluble metal–organic cages (MOCs) are ideal platforms for enhancing antibiotic efficacy through host–guest interactions and mediating the transformation of infected microenvironments due to their defined sizes, shapes, and high modularization of ligands. Here, we have developed a novel water-soluble MOCs crosslinked injectable hydrogel antibacterial platform (GG-ENR@Fe Gel) with multi-mode treatment strategies. In this platform, guar gum (GG), as a carrier, exhibits excellent moisturizing property, biosafety and rapid degradation ability, making it suitable as a medical dressing. Water-soluble MOCs (Fe-1•SO4) was employed in the hydrogel to enhance the solubility and antibacterial efficacy of enrofloxacin (ENR) through host–guest interaction, further triggering additional crosslinking among the GG polymers. Furthermore, after effective adhesion to the infected wound, the Fe-1•SO4 can generate singlet oxygen (1O2) by PDT and rapidly produce massive hydroxyl radicals (•OH) through Fenton-like reaction in the infected microenvironment. This study demonstrates that the water-soluble MOCs is a versatile and synergistic therapeutic platform that can provide promising strategies for treatment of bacterial infections.

A Cages-on-Cluster Structure Constructed by Post-Clustering Covalent Modifications and Guest-Enabled Stimuli-Responsive Luminescence.

A novel gold(I)-cluster-based twin-cage is constructed by post-clustering covalent modification of a hexa-aldehyde cluster precursor with triaminotriethylamines. The cages-on-cluster structure have double cavities and four binding sites, showing site discriminative binding for silver(I) and copper(I) guests. The guests in the tripodal hats affect the luminescence of the cluster: tetra-silver(I) host-guest complex is weak red emissive, while bis-copper(I)-bis-silver(I) one is non-emissive but a stimuli-responsive supramolecule. The copper(I) ion inside the tri-imine cavity is oxidation sensitive, which enable the release of the bright emissive precursor cluster triggered by H2O2 solution. The hybridization of a cluster with cavities to construct a cluster-based cage presents an innovative concept for functional cluster design, and the post-clustering covalent modification opens up new avenues of finely tuning the properties of clusters.

Room‐Temperature Near‐Infrared Phosphorescence from C64 Nanographene Tetraimide by π‐Stacking Complexation with Platinum Porphyrin

Near‐Infrared (NIR) phosphorescence at room temperature is challenging to achieve for organic molecules due to negligible spin–orbit coupling and a low energy gap leading to fast non‐radiative transitions. Here, we show a supramolecular host–guest strategy to harvest the energy from the low‐lying triplet state of C64 nanographene tetraimide 1. 1H NMR and X‐ray analysis confirmed the 1:2 stoichiometric binding of a Pt(II) porphyrin on the two π‐surfaces of 1. While the free 1 does not show emission in the NIR, the host–guest complex solution shows NIR phosphorescence at 77 K. Further, between 860–1100 nm, room temperature NIR phosphorescence (λmax = 900 nm, τavg = 142 µs) was observed for a solid‐state sample drop‐casted from a preformed complex in solution. Theoretical calculations reveal a non‐zero spin–orbit coupling between isoenergetic S1 and T3 of π‐stacked [1·Pt(II) porphyrin] complex. External heavy‐atom‐induced spin–orbit coupling along with rigidification and protection from oxygen in the solid‐state promotes both the intersystem crossing from the first excited singlet state into the triplet manifold and the NIR phosphorescence from the lowest triplet state of 1.

Nitrogen Effects Endowed by Doping Electron-Withdrawing Nitrogen Atoms into Polycyclic Aromatic Hydrocarbon Fluorescence Emitters.

Unveiling innovative mechanisms to design new highly efficient fluorescent materials and, thereby, fabricate high-performance organic light-emitting diodes (OLEDs) is a concerted endeavor in both academic and industrial circles. Polycyclic aromatic hydrocarbons (PAHs) have been widely used as fluorescent emitters in blue OLEDs, but device performances are far from satisfactory. In response, we propose the concept of "nitrogen effects" endowed by doping electron-withdrawing nitrogen atoms into PAH fluorescence emitters. The presence of the n orbital on the imine nitrogen is conducive to promoting electron coupling, which leads to increased molar absorptivity and an accelerated radiative decay rate of emitters, thereby facilitating the Förster energy transfer (FET) process in the OLEDs. Additionally, electronically withdrawing nitrogen atoms enhances host-guest interactions, thereby positively affecting the FET process and the horizontal orientation factor of the emitting layer. To validate the "nitrogen effects" concept, cobalt-catalyzed multiple C-H annulation has been utilized to incorporate alkynes into the imine-based frameworks, which enables various imine-embedded PAH (IE-PAH) fluorescence emitters. The cyclization demonstrates notable regioselectivity, thereby offering a practical tool to precisely introduce peripheral groups at desired positions with bulky alkyl units positioned adjacent to the nitrogen atoms, which were previously beyond reach through the Friedel-Crafts reaction. Blue OLEDs fabricated with IE-PAHs exhibit outstanding performance with a maximum external quantum efficiency (EQEmax) of 32.7%. This achievement sets a groundbreaking record for conventional blue PAH-based fluorescent emitters, which have an EQEmax of 24.0%.

Room-Temperature Near-Infrared Phosphorescence from C64 Nanographene Tetraimide by π-Stacking Complexation with Platinum Porphyrin.

Near-Infrared (NIR) phosphorescence at room temperature is challenging to achieve for organic molecules due to negligible spin-orbit coupling and a low energy gap leading to fast non-radiative transitions. Here, we show a supramolecular host-guest strategy to harvest the energy from the low-lying triplet state of C64 nanographene tetraimide 1. 1H NMR and X-ray analysis confirmed the 1:2 stoichiometric binding of a Pt(II) porphyrin on the two π-surfaces of 1. While the free 1 does not show emission in the NIR, the host-guest complex solution shows NIR phosphorescence at 77 K. Further, between 860-1100 nm, room temperature NIR phosphorescence (λmax = 900 nm, τavg = 142 µs) was observed for a solid-state sample drop-casted from a preformed complex in solution. Theoretical calculations reveal a non-zero spin-orbit coupling between isoenergetic S1 and T3 of π-stacked [1·Pt(II) porphyrin] complex. External heavy-atom-induced spin-orbit coupling along with rigidification and protection from oxygen in the solid-state promotes both the intersystem crossing from the first excited singlet state into the triplet manifold and the NIR phosphorescence from the lowest triplet state of 1.

Single-Molecule Stoichiometry of Supramolecular Complexes.

The use of single-molecule microscopy is introduced as a method to quantify the photophysical properties of supramolecular complexes rapidly at ultra low concentrations (<1 nM), previously inaccessible. Using a model supramolecular system based on the host-guest complexation of cucurbit[n]uril (CB[n]) macrocycles together with a fluorescent guest (Ant910Me), we probe fluorescent CB[n] host-guest complexes in the single molecule regime. We show quantification and differentiation of host-guest photophysics and stoichiometries, both in aqueous media and noninvasively in hydrogel, by thresholding detected photons. This methodology has wide reaching implications in aiding the design of next-generation materials with programmed and controlled properties.