Fullerene-Functionalized Halogen-Bonding Heteroditopic Hosts for Ion-Pair Recognition.

Despite their hydrophobic surfaces with localized π-holes and rigid well-defined architectures providing a scaffold for preorganizing binding motifs, fullerenes remain unexplored as potential supramolecular host platforms for the recognition of anions. Herein, we present the first example of the rational design, synthesis, and unique recognition properties of novel fullerene-functionalized halogen-bonding (XB) heteroditopic ion-pair receptors containing cation and anion binding domains spatially separated by C60. Fullerene spatial separation of the XB donors and the crown ether complexed potassium cation resulted in a rare example of an artificial receptor containing two anion binding sites with opposing preferences for hard and soft halides. Importantly, the incorporation of the C60 motif into the heteroditopic receptor structure has a significant effect on the halide binding selectivity, which is further amplified upon K+ cation binding. The potassium cation complexed fullerene-based receptors exhibit enhanced selectivity for the soft polarizable iodide ion which is assisted by the C60 scaffold preorganizing the potent XB-based binding domains, anion-π interactions, and the exceptional polarizability of the fullerene moiety, as evidenced from DFT calculations. These observations serve to highlight the unique properties of fullerene surfaces for proximal charged guest binding with potential applications in construction of selective molecular sensors and modulating the properties of solar cell devices.

Self-Supporting Hyaluronic Acid-Functionalized G-Quadruplex-Based Perfusable Multicomponent Hydrogels Embedded in Photo-Cross-Linkable Matrices for Bioapplications.

Dynamic G-quadruplex supramolecular hydrogels have aroused great interest in a broad range of bioapplications. However, neither the development of native extracellular matrix (ECM)-derived natural biopolymer-functionalized G-quadruplex hydrogels nor their use to create perfusable self-supporting hydrogels has been explored to date, despite their intrinsic potential as carrier vehicles of therapeutic agents, or even living cells in advanced regenerative therapies, or as platforms to enable the diffusion of nutrients and oxygen to sustain long-term cell survival. Herein, we developed a dynamic co-assembling multicomponent system that integrates guanosine (G), 3-aminophenylboronic acid functionalized hyaluronic acid (HA-PBA), and potassium chloride to bioengineer strong, homogeneous, and transparent HA-functionalized G-quadruplex hydrogels with injectable, thermo-reversible, conductive, and self-healing properties. The supramolecular polymeric hydrogels were developed by hydrogen bonding and π-π stacking interactions between G coupled via dynamic covalent boronate ester bonds to HA-PBA and stabilized by K+ ions, as demonstrated by a combination of experiments and molecular dynamics simulations. The intrinsic instability of the self-assembled G-quadruplex structures was used to bioengineer self-supporting perfusable multicomponent hydrogels with interconnected size and shape-tunable hollow microchannels when embedded in 3D methacrylated gelatin supporting matrices. The microchannel-embedded 3D constructs have shown enhanced cell viability when compared to the bulk hydrogels, holding great promise for being use as artificial vessels for enabling the diffusion of nutrients and oxygen essential for cell survival. The proposed approach opens new avenues on the use of ECM-derived natural biopolymer-functionalized dynamic G-quadruplex hydrogels to design next-generation smart systems for being used in tissue regeneration, drug screening, or organ-on-a-chip.

Selective Potassium Chloride Recognition, Sensing, Extraction, and Transport Using a Chalcogen-Bonding Heteroditopic Receptor.

Chalcogen bonding (ChB) is rapidly rising to prominence in supramolecular chemistry as a powerful sigma (σ)-hole-based noncovalent interaction, especially for applications in the field of molecular recognition. Recent studies have demonstrated ChB donor strength and potency to be remarkably sensitive to local electronic environments, including redox-switchable on/off anion binding and sensing capability. Influencing the unique electronic and geometric environment sensitivity of ChB interactions through simultaneous cobound metal cation recognition, herein, we present the first potassium chloride-selective heteroditopic ion-pair receptor. The direct conjugation of benzo-15-crown-5 ether (B15C5) appendages to Te centers in a bis-tellurotriazole framework facilitates alkali metal halide (MX) ion-pair binding through the formation of a cofacial intramolecular bis-B15C5 M+ (M+ = K+, Rb+, Cs+) sandwich complex and bidentate ChB···X- formation. Extensive quantitative 1H NMR ion-pair affinity titration experiments, solid-liquid and liquid-liquid extraction, and U-tube transport studies all demonstrate unprecedented KCl selectivity over all other group 1 metal chlorides. It is demonstrated that the origin of the receptor's ion-pair binding cooperativity and KCl selectivity arises from an electronic polarization of the ChB donors induced by the cobound alkali metal cation. Importantly, the magnitude of this switch on Te-centered electrophilicity, and therefore anion-binding affinity, is shown to correlate with the inherent Lewis acidity of the alkali metal cation. Extensive computational DFT investigations corroborated the experimental alkali metal cation-anion ion-pair binding observations for halides and oxoanions.

Being Positive is Not Everything - Experimental and Computational Studies on the Selectivity of a Self-Assembled, Multiple Redox-State Receptor that Binds Anions with up to Picomolar Affinities.

The interaction of the self-assembled trinuclear ruthenium bowl 13+ , that displays three other accessible oxidation states, with oxo-anions is investigated. Using a combination of NMR and electrochemical experimental data, estimates of the binding affinities of 14+ , 15+ , and 16+ for both halide and oxo-anions were derived. This analysis revealed that, across the range of oxidation states of the host, both high anion binding affinities (>109  M-1 for specific guests bound to 16+ ) and high selectivities (a range of >107  M-1 ) were observed. As the crystal structure of binding of the hexafluorophosphate anion revealed that the host has two potential binding sites (named the α and ß pockets), the host-guest properties of both putative binding sites of the bowl, in all of its four oxidation states, were investigated through detailed quantum-based computational studies. These studies revealed that, due to the interplay of ion-ion interactions, charge-assisted hydrogen-bonding and anion-π interactions, binding to the α pocket is generally preferred, except for the case of the relatively large and lipophilic hexafluorophosphate anionic guest and the host in the highest oxidation states, where the ß pocket becomes relatively favourable. This analysis confirms that host-guest interactions involving structurally complex supramolecular architectures are driven by a combination of non-covalent interactions and, even in the case of charged binding pairs, simple ion-ion interactions alone cannot accurately define these recognition processes.

Hydrosulfide (HS- ) Recognition and Sensing in Water by Halogen Bonding Hosts.

Hydrogen sulfide (H2 S) plays a crucial signalling role in a variety of physiological systems, existing as the hydrosulfide anion (HS- ) at physiological pH. Combining the potency of halogen bonding (XB) for anion recognition in water with coumarin fluorophore incorporation in acyclic host structural design, the first XB receptors to bind and, more importantly, sense the hydrosulfide anion in pure water in a reversible chemosensing fashion are demonstrated. The XB receptors exhibit characteristic selective quenching of fluorescence upon binding to HS- . Computational DFT and molecular dynamics simulations in water corroborate the experimental anion binding observations, revealing the mode and nature of HS- recognition by the XB receptors.

Hydrazones in anion transporters: the detrimental effect of a second binding site.

Synthetic anion transporters can be developed using anion receptors that are able to bind the anion and stabilize it in the lipophilic interior of a bilayer membrane, and they usually contain functional groups with acidic NHs, such as ureas, thioureas and squaramides. To assess the suitability of acylhydrazones as a new functional group for the preparation of anion transporters, we have studied a family of thioureas functionalized with these and related functional groups. 1H NMR titrations and DFT calculations indicate that the thioureas bearing acylhydrazone groups behave as chloride receptors with two separate binding sites, of which the acylhydrazone binds weaker than the thiourea. Chloride transport studies show that the additional binding site has a detrimental effect on thiourea-based transporters, and this phenomenon is also observed for bis(thio)ureas with two separate binding sites. We propose that the presence of a second anion binding unit hinders the transport activity of the thiourea due to additional interactions with the phospholipids of the membrane. In agreement with this hypothesis, extensive molecular dynamics simulations suggest that the molecules will tend to be positioned in the water/lipid interface, driven by the interaction of the NHs of the thiourea and of the acylhydrazone groups with the POPC polar head groups and water molecules. Moreover, the interaction energies show that the poorest transporters have indeed the strongest interactions with the membrane phospholipids, inhibiting chloride transport. This detrimental effect of additional functional groups on transport activity should be considered when designing new ion transporters, unless these groups cooperatively promote anion recognition and transmembrane transport.

Estrogen receptors in urogenital schistosomiasis and bladder cancer: Estrogen receptor alpha-mediated cell proliferation.

Estrogen-like metabolites have been identified in S. haematobium, the helminth parasite that causes urogenital schistosomiasis (UGS) and in patients´ blood and urine during UGS. Estrogen receptor (ER) activation is enriched in the luminal molecular subtype bladder cancer (BlaCa). To date, the significance of ER to these diseases remains elusive. We evaluated ERα and ERß expression in UGS-related BlaCa (n = 27), UGS-related non-malignant lesions (n = 35), and noninfected BlaCa (n = 80). We investigated the potential of ERα to recognize S. haematobium-derived metabolites by docking and molecular dynamics simulations and studied ERα modulation in vitro using 3 BlaCa cell lines, T24, 5637 and HT1376. ERα was expressed in tumor and stromal cells in approximately 20% noninfected cases and in 30% of UGS-related BlaCa, predominantly in the epithelial cells. Overall, ERα expression was associated with features of tumor aggressiveness such as high proliferation and p53 positive expression. ERα expression correlated with presence of schistosome eggs. ERß was widely expressed in both cohorts but weaker in UGS-related cases. molecular dynamics simulations of the 4 most abundant S. haematobium-derived metabolites revealed that smaller metabolites have comparable affinity for the ERα active state than 17ß-estradiol, while the larger metabolites present higher affinity. Our in vitro findings suggested that ERα activation promotes proliferation in ERα expressing BlaCa cells and that this can be reverted with anti-estrogenic therapy. In summary, we report differential ER expression between UGS-related BlaCa and noninfected BlaCa and provide evidence supporting a role of active ERα during UGS and UGS-induced carcinogenesis.

A polynuclear Cu(ii) complex for real time monitoring of mitochondrial cytochrome C release during cellular apoptosis.

A new amide-imine conjugate, 2-hydroxybenzoic acid-(2-hydroxybenzylidene)-hydrazide (L1), is employed to prepare a single crystal X-ray structurally characterized poly-nuclear Cu(ii) complex (M1). M1 selectively and spatially interacts with cytochrome C (Cyt C) to allow fluorescence imaging of intracellular translocation events in living cells. Thus, direct visualization of a Cyt C translocation event during an apoptotic process is achieved for the first time. The binding constant and LOD are 7.52 × 104 M-1 and 34.0 nM, respectively.

Development of a Library of Thiophene-Based Drug-Like Lego Molecules: Evaluation of Their Anion Binding, Transport Properties, and Cytotoxicity.

The anion-binding and transport properties of an extensive library of thiophene-based molecules are reported. Seventeen bis-urea positional isomers, with different binding conformations and lipophilicities, have been synthesized by appending α- or ß-thiophene or α-, ß-, or γ-benzo[b]thiophene moieties to an ortho-phenylenediamine central core, yielding six subsets of positional isomers. Through 1 H NMR, X-ray crystallography, molecular modelling, and anion efflux studies, it is demonstrated that the most active transporters adopt a pre-organized binding conformation capable of promoting the recognition of chloride, using urea and C-H binding groups in a cooperative fashion. Additional large unilamellar vesicle-based assays, carried out under electroneutral and electrogenic conditions, together with N-methyl-d-glucamine chloride assays, have indicated that anion efflux occurs mainly through an H+ /Cl- symport mechanism. On the other hand, the most efficient anion transporter displays cytotoxicity against tumor cell lines, while having no effects on a cystic fibrosis cell line.

The Green Box: An Electronically Versatile Perylene Diimide Macrocyclic Host for Fullerenes.

The powerful electron accepting ability of fullerenes makes them ubiquitous components in biomimetic donor-acceptor systems that model the intermolecular electron transfer processes of Nature's photosynthetic center. Exploiting perylene diimides (PDIs) as components in cyclic host systems for the noncovalent recognition of fullerenes is unprecedented, in part because archetypal PDIs are also electron deficient, making dyad assembly formation electronically unfavorable. To address this, we report the strategic design and synthesis of a novel large, macrocyclic receptor composed of two covalently strapped electron-rich bis-pyrrolidine PDI panels, nicknamed the "Green Box" due to its color. Through the principle of electronic complementarity, the Green Box exhibits strong recognition of pristine fullerenes (C60/70), with the noncovalent ground and excited state interactions that occur upon fullerene guest encapsulation characterized by a range of techniques including electronic absorption, fluorescence emission, NMR and time-resolved EPR spectroscopies, cyclic voltammetry, mass spectrometry, and DFT calculations. While relatively low polarity solvents result in partial charge transfer in the host donor-guest acceptor complex, increasing the polarity of the solvent medium facilitates rare, thermally allowed full electron transfer from the Green Box to fullerene in the ground state. The ensuing charge separated radical ion paired complex is spectroscopically characterized, with thermodynamic reversibility and kinetic stability also demonstrated. Importantly, the Green Box represents a seminal type of C60/70 host where electron-rich PDI motifs are utilized as recognition motifs for fullerenes, facilitating novel intermolecular, solvent tunable ground state electronic communication with these guests. The ability to switch between extremes of the charge transfer energy continuum is without precedent in synthetic fullerene-based dyads.

Lipidomic analysis of human primary hepatocytes following LXR activation with GW3965 identifies AGXT2L1 as a main target associated to changes in phosphatidylethanolamine.

Liver X receptor (LXR) agonists have the potential to alleviate obesity related diseases, particularly atherosclerosis. However, LXRs are transcriptional regulators that induce de novo lipogenesis and lipid accumulation in hepatocytes which represents a serious adverse effect. In this work, we sought to characterize the LXR agonist GW3965 effects on fatty acid (FA) and phospholipid (PL) remodelling and the correlation with gene expression in order to better understand the underlying effects leading to hepatic pathology upon LXR activation. Human primary hepatocytes treated for 48 h with GW3965 were analysed for changes in lipid metabolism gene expression by qPCR, variations in the FA profile was evaluated by GC-FID and in PL profiles using thin layer chromatography, ESI-MS and MS/MS analysis. Changes in cell membrane biochemical properties were studied using bilayer models generated with CHARMM-GUI. ELOLV6 and SCD1 mRNA increase was consistent with higher C16:1 and C18:1n9 at the expense of C16:0 and C18:0. The reduction of C18:2n6 and increase in C20:2n6 was in agreement with ELOVL5 upregulation. Phosphatydilethanolamine (PE) levels tended to decrease and phosphatidylinositol to increase; although differences did not reach significance, they correlated with changes in AGXT2L1, CDS1 and LPIN1 mRNA levels that were increased. The overall effect of GW3965 on PEs molecular profiles was an increase of long-chain polyunsaturated FA chains and a decrease of C16/C18 saturated and monounsaturated FAs chains. Additionally, PC (32:1) and PC (34:2) were decreased, and PC (36:1) and PC (34:1) were increased. AGXT2L1 is an enzyme with strict substrate specificity for phosphoethanolamine, which is converted into ammonia in GW3965-treated hepatocytes and could explain the PE reduction. In summary, LXR activation by GW3965 targets PE biosynthesis and FA elongation/desaturation, which tends to decrease PE in relation to total PL levels, and remodelling of PC and PE molecular species. We identified the human AGXT2L1 gene as induced by LXR activation by both synthetic and endogenous agonist treatment. The increase in acetaldehyde-induced oxidative stress, and in the lipid species identified have the potential to enhance the inflammatory process and impair membrane function. Future studies should focus on inhibition of AGXT2L1 activity with the aim of reverting the steatosis induced by LXR activation.

Molybdenum(ii) complexes with p-substituted BIAN ligands: synthesis, characterization, biological activity and computational study.

New complexes [Mo(η3-C3H5)X(CO)2(4-Y-BIAN)] (4-Y-BIAN = bis(4-Y-phenyl)-acenaphthenequinonediimine), with X = Br and Y = H, Me, OMe, COOH and X = Cl, Y = OMe, as well as the cation with X = NCMe and Y = OMe were synthesized, expanding the scope of this family. Two single crystal X-ray structures (X = Br, Y = Me, OMe) display a less symmetric arrangement (axial isomer), where one N donor atom is trans to the allyl group and the second to one CO. DFT studies showed similar energies for the two possible isomers of the complexes, with a very small preference for the observed axial isomer. The HOMO of the complexes is localized in the metal and the HOMO-1 of the oxidized species has a contribution from the BIAN ligand, while the LUMO is fully localized in BIAN. Electrochemical studies showed one process corresponding to the oxidation of Mo(ii) to Mo(iii) for complexes with X = Br, Y = H, Me, and two oxidation reactions for those with X = Br, Y = Cl, OMe, while the COOH derivative exhibited no oxidation wave. The antitumor effect of the complexes with X = Br was tested in cancer lines, and the H and OMe complexes were particularly active, with EC50 values below 8 µM in HeLa cell lines. The DNA binding constants determined by titration experiments were comparable with those of doxorubicin and ethidium bromide, suggesting a mechanism of action based on intercalation in DNA.

Fluorinated synthetic anion carriers: experimental and computational insights into transmembrane chloride transport.

A series of fluorinated tripodal tris-thioureas function as highly active anion transporters across lipid bilayers and cell membranes. Here, we investigate their mechanism of action using anion transport assays in cells and synthetic vesicles and molecular modelling of transporter-lipid interactions. When compared with non-fluorinated analogues, fluorinated compounds demonstrate a different mechanism of membrane transport because the free transporter cannot effectively diffuse through the membrane. As a result, in H+/Cl- cotransport assays, fluorinated transporters require the presence of oleic acid to form anionic oleate complexes for recycling of the transporter, whereas non-fluorinated analogues readily diffuse through the membrane as free transporters and show synergistic transport with the proton transporter gramicidin. Molecular dynamics simulations revealed markedly stronger transporter-lipid interactions for fluorinated compounds compared with non-fluorinated analogues and hence, higher energy barriers for fluorinated compounds to cross the membrane as free transporters. With use of appropriate proton transporters to ensure measurement of the correct rate-limiting steps, the transport rates determined in synthetic vesicle assays show excellent agreement with the anion transport rates determined in cell-based assays. We conclude that integration of computational and experimental methods provides a strategy to optimise transmembrane anion transporter design for biomedical applications.

Anion Recognition in Water by Charge-Neutral Halogen and Chalcogen Bonding Foldamer Receptors.

A novel strategy for the recognition of anions in water using charge-neutral σ-hole halogen and chalcogen bonding acyclic hosts is demonstrated for the first time. Exploiting the intrinsic hydrophobicity of halogen and chalcogen bond donor atoms integrated into a foldamer structural molecular framework containing hydrophilic functionalities, a series of water-soluble receptors was constructed for an anion recognition investigation. Isothermal titration calorimetry (ITC) binding studies with a range of anions revealed the receptors to display very strong and selective binding of large, weakly hydrated anions such as I- and ReO4-. This is achieved through the formation of 2:1 host-guest stoichiometric complex assemblies, resulting in an encapsulated anion stabilized by cooperative, multidentate, convergent σ-hole donors, as shown by molecular dynamics simulations carried out in water. Importantly, the combination of multiple σ-hole-anion interactions and hydrophobic collapse results in I- affinities in water that exceed all known σ-hole receptors, including cationic systems (ß2 up to 1.68 × 1011 M-2). Furthermore, the anion binding affinities and selectivity trends of the first example of an all-chalcogen bonding anion receptor in pure water are compared with halogen bonding and hydrogen bonding receptor analogues. These results further advance and establish halogen and chalcogen bond donor functions as new tools for overcoming the challenging goal of anion recognition in pure water.

New Molybdenum(II) Complexes with α-Diimine Ligands: Synthesis, Structure, and Catalytic Activity in Olefin Epoxidation.

Three new complexes [Mo(η³-C3H5)Br(CO)2{iPrN=C(R)C5H4N}], where R = H (IMP = N-isopropyl 2-iminomethylpyridine), Me, and Ph, were synthesized and characterized, and were fluxional in solution. The most interesting feature was the presence, in the crystal structure of the IMP derivative, of the two main isomers (allyl and carbonyls exo), namely the equatorial isomer with the Br trans to the allyl and the equatorial with the Br trans to one carbonyl, the position trans to the allyl being occupied by the imine nitrogen atom. For the R = Me complex, the less common axial isomer was observed in the crystal. These complexes were immobilized in MCM-41 (MCM), following functionalization of the diimine ligands with Si(OEt)3, in order to study the catalytic activity in olefin epoxidation of similar complexes as homogeneous and heterogeneous catalysts. FTIR, 13C- and 29Si-NMR, elemental analysis, and adsorption isotherms showed that the complexes were covalently bound to the MCM walls. The epoxidation activity was very good in both catalysts for the cis-cyclooctene and cis-hex-3-en-1-ol, but modest for the other substrates tested, and no relevant differences were found between the complexes and the Mo-containing materials as catalysts.

Oxovanadium(V) and Dioxomolybdenum(VI) Complexes of Amide-Imine Conjugates: Structures, Catalytic and Antitumor Activities.

Three new amide-imine conjugates, namely [(E)-2-hydroxy-N'-((2-hydroxynaphthalen-1-yl)methylene)benzohydrazide] (SALNP), [(E)-N'-(4-(diethylamino)-2-hydroxybenzylidene)-2-hydroxybenzohydrazide] (SALSD), and [(E)-N'-(3-ethoxy-4-hydroxybenzylidene)-2-hydroxybenzohydrazide] (SALVN), derived by reacting 2-hydroxybenzohydrazide (SAL) with three different aldehyde, 2-hydroxynapthaldehyde, 4-(diethylamino)-2-hydroxybenzaldehyde, and 3-ethoxy-4-hydroxybenzaldehyde, respectively. Three mononuclear oxovanadium(V) and two µoxo-bridged dinuclear molybdenum(VI) complexes have been synthesized using SALNP and SALSD. Besides, SALVN is used to prepare oxovanadium(V) and dioxomolybdenum(VI) complexes. All five metal complexes along with three amide-imine conjugates are characterized by single crystal XRD analysis. Some of them have been explored as catalyst for oxidation of alkyl benzene and styrene. Antitumor activities of the metal complexes along with ligands have been studied on Dalton lymphoma (DL) and 2PK3 murine lymphoma cells.

Exploring Anticancer and (Bio)catalytic Activities of New Oxovanadium(V), Dioxomolybdenum(VI), and Copper(II) Complexes of Amide-Imine Conjugates.

An amide-imine conjugate, (E)-N'-((2-hydroxynaphthalen-1-yl) methylene)-4-methylbenzohydrazide (PTANAP), derived from 4-methyl-benzoic acid hydrazide (PTA) and 2-hydroxynapthaldehyde, is explored to prepare dinuclear oxovanadium(V), mononuclear dioxomolydenum(VI), and Cu(II) complexes. Single crystal X-ray structurally characterized complexes have been exploited as catalyst for oxidation of ethylbenzene, catechol, and o-aminophenol. The anticancer properties of the oxo-vanadium complex have been explored against human leukemia cell (K-562) and mouse lymphoma cells (2PK3).

Exploring aggregation-induced emission through tuning of ligand structure for picomolar detection of pyrene.

Tuning of ligand structures through controlled variation of ring number in fused-ring aromatic moiety appended to antipyrine allows detection of 7.8 × 10-12  M pyrene via aggregation-induced emission (AIE) associated with 101-fold fluorescence enhancement. In one case, antipyrine unit is replaced by pyridine to derive bis-methylanthracenyl picolyl amine. The structures of four molecules have been confirmed by single crystal X-ray diffraction analysis. Among them, pyrene-antipyrine conjugate (L) undergoes pyrene triggered inhibition of photo-induced electron transfer (PET) leading to water-assisted AIE.

Exploring (bio)catalytic activities of structurally characterised Cu(ii) and Mn(iii) complexes: histidine recognition and photocatalytic application of Cu(ii) complex and derived CuO nano-cubes.

Structurally characterised two polymeric complexes of Cu(ii) (3) and Mn(iii) (4) of the ligand L (2-(((2-(phenylamino)ethyl)imino)methyl)phenol) have been explored for catecholase-like activity, fluorescence recognition of histidine and catalytic activity towards coupling of aryl iodides with benzamide, leading to N-arylbenzamides. CuO nano-cubes (NCs) prepared by thermal decomposition of the Cu(ii) complex function as photocatalysts for the degradation of methylene blue. Cube-like morphology of CuO nanocrystal and flake-shaped micrometer order Cu(ii) complex have been established from the field emissive scanning electron microscopy (FESEM) images.

Chiral halogen and chalcogen bonding receptors for discrimination of stereo- and geometric dicarboxylate isomers in aqueous media.

Novel chiral halogen and chalcogen bonding receptors exhibit different selectivities for stereo- and geometric dicarboxylate isomers compared to a hydrogen bonding analogue. The unique geometric and electronic properties of the chalcogen bonding receptor facilitate the diagnostic fluorescence sensing of geometric dicarboxylate isomer guest species.