Hydrogen Bond Acceptor Sites Research Articles

Enhanced aggregation induced emission by H-bond between the barbiturate molecules containing hydroxyl group

Barbiturates had been widely studied as a molecule with aggregation induced emission (AIE) phenomenon, but barbiturates as a group with multiple hydrogen bond donor and acceptor sites, the relationship between intermolecular hydrogen bond and AIE phenomenon has not been mainly studied. In this paper, a new barbiturate fluorescence molecule BNOH with hydroxyl group was designed and synthesized in order to analyze the relationship between hydrogen bond and molecular AIE phenomenon by increasing the functional group (–OH) that was easy to form hydrogen bond. By spectroscopic analysis, BNOH had structural torsion in aqueous mixed solution, which led to fluorescence decrease, while in aprotic mixed solvent, there was strong AIE phenomenon. DFT and TD-DFT calculations at the B3LYP/6-31G (d) were performed for a deeper understanding of optical transitions. In addition, in order to investigate the difference of its fluorescence phenomenon, two other barbiturate derivatives were synthesized and their spectra were compared with BNOH. The relationship between hydrogen bond and AIE phenomenon of barbiturates was proved, and the fluorescence mechanism of BNOH in organic solvent was proposed and determined. We believe that this study will not only increase the understanding of barbiturate AIE compounds, but also contribute to the study of the important role of hydrogen bonds in the fluorescence phenomenon of barbiturate AIE compounds.

The Impact of Water as an Additive on the Elution of Some Basic Organic Compounds in Supercritical Fluid Chromatography.

In this study, water was used as an additive in the methanol-modified carbon dioxide-based eluent for the elution of some basic organic compounds from a hybrid silica column via supercritical fluid chromatography (SFC). The experiments were applied to sulfonamides, propranolol, and other organic nitrogen compounds involving aromatic rings from different classes of amine, pyrimidine, and purine with different pKa values (the pKa values for the studied analytes range from 4.6 to 10.4). The results revealed different responses to the different percentages of water addition. Adding 1~2% of water to the modifier (methanol) led to a positive effect manifested by more symmetrical peak shapes and reduced retention times for most compounds. The key factor for this improvement in the properties of chromatographic peaks is due to the adsorption of water on the silanol groups of the stationary phase, consequently resembling the phenomena observed in hydrophilic interaction liquid chromatography (HILIC). Moreover, the availability of hydrogen bond acceptor and donor sites in the analyte structure is an important factor to be considered when adding water as an additive to the modifier for improving the chromatographic peaks. However, introducing water in an amount higher than 3% resulted in perturbed chromatographic signals. It was also found that water as an additive alone could not successfully elute propranolol from the hybrid silica column with an acceptable peak shape; thus, the addition of a strong base such as amine salts was also necessary. The proposed use of a particular amount of water in the mobile phase could have a positive effect compared to the same mobile phase without water, improving the chromatographic peak properties of the elution of some basic organic compounds from the hybrid silica column.

Screening ionic liquids based on COSMO-SAC model for extracting organic sulfur from coal and mechanism study

Screening suitable ionic liquids（ILs） for removing organic sulfur compounds from coal and discovering new, effective and environmentally friendly coal desulfurization additives is crucial. The solubility properties (SP) of six organic sulfur model compounds (OSMCs) in imidazole ILs were calculated based on the COSMO-SAC model. The results showed that 2-thiophenecarboxylic acid and 2-aminophenyl phenyl sulfone exhibited favorable solubility properties in certain ILs. The solubility properties of partial imidazole ILs consisting of [Cl]- were significantly better than other anions. Through the σ -profiles analysis of ILs anions, cations and OSMCs, it showed that [Cl]- had a higher tendency to be hydrogen bond acceptor than other anions. The polar groups in OSMCs increased the hydrogen bond donor or acceptor sites for interactions with ILs, while extended the optional range of ILs for hydrogen bond interactions with OSMCs. The extraction efficiencies of 2-thiophenecarboxylic acid by ILs were above 25%, with [DMIM][Cl] displaying the highest efficiency at 47.5%. Meanwhile, [DMIM][Cl] was the most effective extractant for removing all OSMCs except benzothiophene, which was basically consistent with the calculation results. Electrostatic potential analysis was used to obtain the sites where OSMCs are the most likely to form hydrogen bond interactions with [DMIM][Cl]. And characterization of hydrogen bond formation between ILs and OSMCs was obtained by FTIR analysis. The hydrogen bond formed by p-thiocresol with [DMIM][Cl] is weak, and the hydrogen bonds formed by 2-thiophenecarboxylic acid, 2-aminophenyl phenyl sulfone with [DMIM][Cl] are relatively strong. The analysis of intermolecular hydrogen bond interactions verified the mechanism underlying the excellent extraction performance for specific OSMCs by the selected ILs.

Highly acidic N-triflylphosphoramides as chiral Brønsted acid catalysts: the effect of weak hydrogen bonds and multiple acceptors on complex structures and aggregation.

N-Triflylphosphoramides (NTPAs) represent an important catalyst class in asymmetric catalysis due to their multiple hydrogen bond acceptor sites and acidity, which is increased by several orders of magnitude compared to conventional chiral phosphoric acids (CPAs). Thus, NTPAs allow for several challenging transformations, which are not accessible with CPAs. However, detailed evidence on their hydrogen bonding situation, complex structures and aggregation is still lacking. Therefore, this study covers the hydrogen bonding behavior and structural features of binary NTPA/imine complexes compared to their CPA counterparts. Deviating from the single-well potential hydrogen bonds commonly observed in CPA/imine complexes, the NTPA/imine complexes exhibit a tautomeric equilibrium between two proton positions. Low-temperature NMR at 180 K supported by computer simulations indicates a OHN hydrogen bond between the phosphoramide oxygen and the imine, instead of the mostly proposed NHN H-bond. Furthermore, this study finds no evidence for the existence of dimeric NTPA/NTPA/imine complexes as previously suggested for CPA systems, both synthetically and through NMR studies.

Fluorinated Isoindolinone-Based Glucosylceramide Synthase Inhibitors with Low Human Dose Projections.

Inhibition of glucosylceramide synthase (GCS) has been proposed as a therapeutic strategy for the treatment of Parkinson's Disease (PD), particularly in patients where glycosphingolipid accumulation and lysosomal impairment are thought to be contributing to disease progression. Herein, we report the late-stage optimization of an orally bioavailable and CNS penetrant isoindolinone class of GCS inhibitors. Starting from advanced lead 1, we describe efforts to identify an improved compound with a lower human dose projection, minimal P-glycoprotein (P-gp) efflux, and acceptable pregnane X receptor (PXR) profile through fluorine substitution. Our strategy involved the use of predicted volume ligand efficiency to advance compounds with greater potential for low human doses down our screening funnel. We also applied minimized electrostatic potentials (Vmin) calculations for hydrogen bond acceptor sites to rationalize P-gp SAR. Together, our strategies enabled the alignment of a lower human dose with reduced P-gp efflux, and favorable PXR selectivity for the discovery of compound 12.

Hydrogen-Bonded Complexes in Binary Mixture of Imidazolium-Based Ionic Liquids with Organic Solvents.

Though local structures in ionic liquids are dominated by strong Coulomb forces, directional hydrogen bonds can also influence the physicochemical properties of imidazolium-based ionic liquids. In particular, the C-2 position of the imidazolium cation is acidic and can bind with suitable hydrogen bond acceptor sites of molecular solvents dissolved in imidazolium-based ionic liquids. In this report, we identify hydrogen-bonded microenvironments of the model ionic liquid, 1-ethyl-3-methylimidazolium tris(pentafluoroethyl) trifluorophosphate, and the changes that occur when molecular solvents are dissolved in it by using a C-D infrared reporter at the C-2 position of the cation. Our linear and nonlinear infrared experiments, along with computational studies, indicate that the molecular solvent dimethyl sulfoxide can form strong hydrogen-bonded dimers with the cation of the ionic liquid at the C-2 position. In contrast, acetone, which is also a hydrogen bond acceptor similar to dimethyl sulfoxide, does not show evidence of cation-solvent hydrogen-bonded conformers at the C-2 position. The outcome of our study on a broad scale strengthens the importance of cation-solute interactions in ionic liquids.

(Invited) Hole-Transporting Materials for Perovskite Solar Cells: A Theoretical Insight

Hole-transporting materials (HTMs) are a crucial component in obtaining high power conversion efficiencies (PCEs) in perovskite-based solar cells (PSCs). They play the important roles of extracting the photogenerated holes, formed within the perovskite film, and transporting them to the electrodes. Among the wide number of chemical structures proposed as HTMs for PSCs, small organic molecules have received special attention with spiro-OMeTAD (2,2´,7,7´-tetrakis(N,N-di-p-methoxyphenylamine)-9,9´-spirobifluorene) as a reference.1 In this communication, we first focus on how the donor ability and hole reorganization energy change with the chemical structure of the HTM. Sulfur-rich compounds, such as the anthracene-tetrathiophene ATT-OMe system displayed in Figure 1a, that have been used as HTMs in PSCs achieving remarkable PCEs, are theoretically described.2 Second, we investigate a series of HTMs based on fused polyheteroaromatic molecules incorporating 7-azaindole terminal moieties bearing hydrogen-bond donor and hydrogen-bond acceptor sites (Figure 1b). The 7-azaindole units induce the hydrogen-bond self-assembly of the conjugated molecules thus increasing the supramolecular ordering in the HTM layer. The effects of this ordering on the charrier transport in the HTM semiconducting layer are theoretically discussed.3 Third, we briefly present how the optical properties (energy bandgap) of Cs2AgBiBr6 lead-free double perovskites can be tuned by substituting the monovalent Ag1+ and trivalent Bi3+ cations by divalent Sn2+, Ge2+ and Zn2+ cations.4 Figure 1. Chemical structure of the sulfur-rich ATT-OMe (a) and the H-bond-promoting ADAI (b) HTM molecules. Both HTMs are based on an anthracene central core. References J. Urieta, I. García-Benito, A. Molina-Ontoria, N. Martín, Chem. Soc. Rev. 2016, 47, 8541.I. Zimmermann, J. Urieta-Mora, P. Gratia, J. Aragó, G. Grancini, A. Molina-Ontoria, E. Ortí, N. Martín, M. K. Nazeeruddin, ACS Appl. Mater. Interfac. 2017, 7, 1601674.P. Gómez, S. Georgakopoulos, M. Más-Montoya, J. Cerdá, J. Pérez, E. Ortí, J. Aragó, D. Curiel, J. Mater. Chem. C 2021, 13, 8620.P. Sebastiá-Luna, J. Calbo, N. Albiach-Sebastián, M. Sessolo, F. Palazón, E. Ortí, H. J. Bolink, Chem. Mater. 2021, 33, 8028. Figure 1

Maytenus octogona Superoxide Scavenging and Anti-Inflammatory Caspase-1 Inhibition Study Using Cyclic Voltammetry and Computational Docking Techniques.

The relationship between oxidative stress and inflammation is well known, and exogenous antioxidants, primarily phytochemical natural products, may assist the body's endogenous defense systems in preventing diseases due to excessive inflammation. In this study, we evaluated the antioxidant properties of ethnomedicines from Peru that exhibit anti-inflammatory activity by measuring the superoxide scavenging activity of ethanol extracts of Maytenus octogona aerial parts using hydrodynamic voltammetry at a rotating ring-disk electrode (RRDE). The chemical compositions of these extracts are known and the interactions of three methide-quinone compounds found in Maytenus octogona with caspase-1 were analyzed using computational docking studies. Caspase-1 is a critical enzyme triggered during the activation of the inflammasome and its actions are associated with excessive release of cytokines. The most important amino acid involved in active site caspase-1 inhibition is Arg341 and, through docking calculations, we see that this amino acid is stabilized by interactions with the three potential methide-quinone Maytenus octogona inhibitors, hydroxytingenone, tingenone, and pristimerin. These findings were also confirmed after more rigorous molecular dynamics calculations. It is worth noting that, in these three compounds, the methide-quinone carbonyl oxygen is the preferred hydrogen bond acceptor site, although tingenone's other carbonyl group also shows a similar binding energy preference. The results of these calculations and cyclovoltammetry studies support the effectiveness and use of anti-inflammatory ethnopharmacological ethanol extract of Maytenus octogona (L'Héritier) DC.

Effect of molecular structure on the adsorption behavior of sulfanilamide antibiotics on crumpled graphene balls

Since the 1930s, sulfonamide(SA)-based antibiotics have served as important pharmaceuticals, but their widespread detection in water systems threatens aquatic organisms and human health. Adsorption via graphene, its modified form (graphene oxide, GO), and related nanocomposites is a promising method to remove SAs, owing to the strong and selective surface affinity of graphene/GO with aromatic compounds. However, a deeper understanding of the mechanisms of interaction between the chemical structure of SAs and the GO surface is required to predict the performance of GO-based nanostructured materials to adsorb the individual chemicals making up this large class of pharmaceuticals. In this research, we studied the adsorptive performance of 3D crumpled graphene balls (CGBs) to remove 10 SAs and 13 structural analogs from water. The maximum adsorption capacity qm of SAs on CGB increased with the number of (1) aromatic rings; (2) electron-donating functional groups; (3) hydrogen bonding acceptor sites. Furthermore, the CGB surface displayed a preference for homocyclic relative to heterocyclic aromatic structures. A leading mechanism, π-π electron-donor-acceptor interaction, combined with hydrogen bonding, explains these trends. We developed a multiple linear regression model capable of predicting the qm as a function of SA chemical structure and properties and the oxidation level of CGB. The model predicted the adsorptive behaviors of SAs well with the exception of a chlorinated/fluorinated SA. The insights afforded by these experiments and modeling will aid in tailoring graphene-based adsorbents to remove micropollutants from water and reduce the growing public health threats associated with antibiotic resistance and endocrine-disrupting chemicals.

Two-Dimensional Self-Assembly Driven by Intermolecular Hydrogen Bonding in Benzodi-7-azaindole Molecules on Au(111).

The control of molecular structures at the nanoscale plays a critical role in the development of materials and applications. The adsorption of a polyheteroaromatic molecule with hydrogen bond donor and acceptor sites integrated in the conjugated structure itself, namely, benzodi-7-azaindole (BDAI), has been studied on Au(111). Intermolecular hydrogen bonding determines the formation of highly organized linear structures where surface chirality, resulting from the 2D confinement of the centrosymmetric molecules, is observed. Moreover, the structural features of the BDAI molecule lead to the formation of two differentiated arrangements with extended brick-wall and herringbone packing. A comprehensive experimental study that combines scanning tunneling microscopy, high-resolution X-ray photoelectron spectroscopy, near-edge X-ray absorption fine structure spectroscopy, and density functional theory theoretical calculations has been performed to fully characterize the 2D hydrogen-bonded domains and the on-surface thermal stability of the physisorbed material.

4,4′-Azobis(1,2,4-triazole): A Versatile Molecular Scaffold to Develop Tailor-Made Energetic Materials

Energetic materials containing azoles are appealing in terms of their high nitrogen content and presence of functional groups that can participate in different non-covalent bonding interactions. One such interesting compound is 4,4′-azobis(1,2,4-triazole) (ATRZ), which has formidable energetic parameters. Based on the presence of hydrogen-bond acceptor and metal coordination sites, a number of tailor-made energetic materials have been derived by employing ATRZ as the molecular precursor. In this review, we discuss the use of this high-energy molecular scaffold in the development of different energetic cocrystals, coordination polymers, and composites and discuss their properties in the context of state-of-the-art energetic materials.

Experimental and Theoretical Investigation of Hydrogen-Bonding Interactions in Cocrystals of Sulfaguanidine.

Pharmaceutical cocrystals, a type of multicomponent crystalline material incorporating two or more molecular and/or ionic compounds connected by noncovalent interactions (such as hydrogen bonds, π-π interactions, and halogen bonds), are attracting increasing attention in crystal engineering. Sulfaguanidine (SGD), one of the most frequently used sulfonamide compounds, was chosen as a model compound in this work to further investigate the hydrogen bond interactions in cocrystals, since it possesses various hydrogen bond donor and acceptor sites. Five cocrystals of SGD, synthesized successfully by slurry and slow evaporation methods, were fully characterized by thermal analysis, X-ray techniques, and Fourier transform infrared spectroscopy. To gain insight into the nature of hydrogen-bonding interactions, theoretical calculations including the analysis of Hirshfeld surface, MEPS (molecular electrostatic potential surface), and QTAIM (quantum theory of atoms in molecules) were conducted. The results are a part of a systematic study of cocrystals of sulfonamides that aims to establish synthon hierarchies in cocrystals containing molecules with multiple hydrogen-bonding functional groups.

Greener and scalable synthesis of N-methyl imines using a sustainable functional polymer

N-Methyl imines, as simple Schiff bases, could be prepared using a more sustainable and greener system, including a 33 wt.% solution of methylamine in absolute ethanol, and poly(N-vinylimidazole) (PVIm) at room temperature within 45–60 min. PVIm is a biocompatible, biodegradable and water-soluble synthetic solid functional polymer. It was indicated that PVIm can act as a reagent with multiple tasks in this reaction, including (a) reducing activation energy and stabilizing the transition states through hydrogen bond acceptor sites and low acidity of C(2)–H and (b) dehydrating activity through trapping of the released water molecules as the association phase. Inexperienced chemists can handle it easily because it is solid and less toxic than conventional catalysts – that is, piperidine, pyridine or metal- or halogen-containing salts. Additionally, ethanol and PVIm could be recycled and reused in subsequent runs without any further purification. The regenerated PVIm demonstrated stable activity after several recycle runs. No changes were detected in its chemical structure, as confirmed by Fourier transform infrared and nuclear magnetic resonance spectrum analyses.

Ethidium hepta-fluoro-butyrate.

In the title compound (systematic name: 3,8-diamino-5-ethyl-6-phenylphenanthridin-5-ium 2,2,3,3,4,4,4-heptafluorobutyrate), C21H20N3 +·C4F7O2 -, two ethidium ions, C21H20N3 + form a dimerized structure due to π-π inter-actions, even though they are positively charged. The hepta-fluoro-butyrate anions are connected to neighbouring cation dimers via hydrogen-bonding inter-actions, the hydrogen-bonding donor sites of the -NH2 groups of the ethidium ions connecting to the hydrogen-bonding acceptor sites of the -COO- groups of the hepta-fluoro-butyrate anions.

Metal‐Free, Biomass‐Derived Nano‐Architectured Carbon Quantum Dots as an Efficient Acid‐Base Bifunctional Catalyst for Facile Synthesis of Benzo[g]chromene and Pyrimidine Analogs

AbstractPerusal of literature reports revealed that variedly functionalized carbon quantum dots (CQDs) have been extensively studied as sustainable alternative to conventional nanomaterials in catalysis. In this context, herein, we have designed and developed an efficient, metal free, green and heterogeneous sulfonic acid functionalized carbon quantum dots (CQDs)‐based catalyst derived from biomass for one pot multicomponent reactions. The developed catalyst has been fully characterized using various techniques such as DLS, IR spectroscopy and zeta potential measurements. The synthesized catalyst acts as a bipolar catalyst which can activate all the three components via hydrogen bond donor as well as hydrogen bond acceptor sites in the reaction mixture, to synthesize pyrimidine and 4H‐benzo[g]chromene derivatives in pure aqueous medium. Further, the catalyst exhibits significant reusability up to six cycles without any significant loss in its catalytic activity. Therefore, an economical and sustainable protocol has been developed for facile syntheses of biologically important heterocycles through an efficient and easily recoverable biomass derived catalyst in pure aqueous medium. Apparently, the developed strategy provides good eco‐scale and E‐factor values, which are acceptable according to green chemistry protocols.

Polyphosphoester/Tannic Acid Composite Sticky Coacervates as Adhesives

Abstract To obtain adhesive coacervates with biodegradable polymers, sticky coacervates composed of water soluble polyphosphoester (PPE) and tannic acid (TA) were prepared. According to the multiple hydrogen bonding acceptor sites in the repeating unit of PPE, a coacervate can spontaneously form by mixing PPE with TA in aqueous media. The coacervate could work as an adhesive for titanium plates. Furthermore, an average maximum shear bond strength of 1.6 MPa was observed.

Zwitterionic Luminescent 2D Metal-Organic Framework Nanosheets (LMONs): Selective Turn-On Fluorescence Sensing of Dihydrogen Phosphate.

While a plethora of organic linkers based on carboxylic acids have been utilized in the construction of MOFs, zwitterionic linkers that typify the attributes of naturally occurring amino acids have been exploited only scarcely to the best of our knowledge. Zwitterionic interior characteristics should be expected to impart unique properties to the resultant MOFs with a high potential to interact with guest species through electrostatic interactions. In our investigations with bis(p-carboxyphenyl)imidazolylarenes as a novel class of linkers for the development of functional MOFs, we have found that bisimidazole-tetracarboxylic acid H4DMBI undergoes metal-assisted self-assembly with Zn(NO3)2 to yield a layered MOF (Zn-DMBI). In the latter, the linker serves as a two-connecting linker with imidazoles and carboxylic acids behaving as zwitterions. The layers are offset stacked in the crystal structure and are bound firmly by hydrogen bonds between imidazolium and carboxylate ions. Such a packing precludes fluorescence from being observed due to self-quenching. However, exfoliation into zwitterionic 2D metal-organic nanosheets (MONs) by sonication in methanol for 1 h liberates palpable fluorescence. Furthermore, the suspension of luminescent MONs (LMONs) in methanol permits selective sensing of anions; in particular, dihydrogen phosphate (H2PO4-) that is complementary to the zwitterions in terms of hydrogen bond donor and acceptor sites is observed with fluorescence enhancement by 120%, leading to its detection at a sub-parts-per-million (0.13 ppm) level. Thus, access to zwitterionic 2D MONs and their application for selective anion sensing with "turn-on" fluorescence are demonstrated by a rational de novo bottom-up approach.

Immobilized Supramolecular Systems as Efficient Synzymes for CO2 Activation and Conversion

AbstractSupramolecular catalysis can provide distinct advantages for the catalytic conversion of CO2 into carbonates by cycloaddition to epoxides. For example, the absence of metals in the catalytic site, and the easy design for optimization. The incorporation of multiple functionalities in pseudopeptidic macrocycles with a pendant arm allows catalytic systems to be obtained where halide anions (nucleophilic activating agents for epoxides), hydrogen bond acceptor sites (activating agents for epoxides and stabilizing sites for anionic intermediates), and amine groups (Lewis basic sites for activating CO2) are in proximity. This allows a high activity in the cycloaddition of CO2 to styrene oxide under mild conditions (turnover number (TON) = 900, CO2 balloon, 100 °C, 5 h). The primary amino groups in the arm facilitate the immobilization of these macrocyclic structures in cross‐linked polymeric matrices containing ammonium halide fragments. Such multifunctional insoluble polymers afford excellent catalytic results with high TON and turnover frequency values and remarkable productivities (>10 gprod gresin−1 h−1). This activity is maintained for a variety of epoxides and is retained after several catalytic runs. Their performance is significantly higher than those reported for most heterogenous supramolecular catalytic systems for CO2 transformation into carbonates.

Studying the impact of the pre-exponential factor on templated nucleation.

Traditionally, the enhancement of nucleation rates in the presence of heterogeneous surfaces in crystallisation processes has been attributed to the modification of the interfacial energy of the system according to the classical nucleation theory. However, recent developments have shown that heterogeneous surfaces instead alter the pre-exponential factor of nucleation. In this work, the nucleation kinetics of glycine and diglycine in aqueous solutions have been explored in the presence and absence of a heterogeneous surface. Results from induction time experiments show that the presence of a heterogeneous surface increases the pre-exponential factor by 2-fold or more for both glycine and diglycine, while the interfacial energy remains unchanged for both species. This study suggests that the heterogeneous surface enhances the nucleation rate via hydrogen bond formation with both glycine and diglycine. This is verified by hydrogen bond propensity calculations, molecular functionality analysis, and calculation of the time taken for a solute molecule to attach to the growing nucleus, which is an order of magnitude shorter than the estimated lifetime of the hydrogen bond. The effect of the heterosurface is of greater magnitude for diglycine than for glycine, which may be due to the heightened molecular complementarity between the hydrogen bond donor and acceptor sites on diglycine and the heterosurface.

Toxicity and mode of action of the aporphine plant alkaloid liriodenine on the insect GABA receptor

Liriodenine is a biologically active plant alkaloid with multiple effects on mammals, fungi, and bacteria, but has never been evaluated for insecticidal activity. Accordingly, liriodenine was applied topically in ethanolic solutions to adult female Anopheles gambiae, and found to be mildly toxic. Its lethality was synergized in mixtures with dimethyl sulfoxide and piperonyl butoxide. Recordings from the ventral nerve cord of larval Drosophila melanogaster showed that liriodenine was neuroexcitatory and reversed the inhibitory effect of 1 mM GABA at effective concentrations of 20–30 μM. GABA antagonism on the larval nervous system was equally expressed on both susceptible and cyclodiene-resistant rdl preparations. Acutely isolated neurons from Periplaneta americana were studied under patch clamp and inhibition of GABA-induced currents with an IC50 value of about 1 μM were observed. In contrast, bicuculline did not reverse the effects of GABA on cockroach neurons, as expected. In silico molecular models suggested reasonable structural concordance of liriodenine and bicuculline and isosteric hydrogen bond acceptor sites. This study is the first assessing of the toxicology of liriodenine on insects and implicates the GABA receptor as one likely neuronal target, where liriodenine might be considered an active chemical analog of bicuculline.