Transient Metallo-Lipidoid Assemblies Amplify Covalent Catalysis of Aqueous and Non-Aqueous Reactions.

Dissipative supramolecular assemblies are hallmarks of living systems, contributing to their complex, dynamic structures and emerging functions. Living cells can spatiotemporally control diverse biochemical reactions in membrane compartments and condensates, regulating metabolite levels, signal transduction or remodeling of the cytoskeleton. Herein, we constructed membranous compartments using self-assembly of lipid-like amphiphiles (lipidoid) in aqueous medium. The new double-tailed lipidoid features Cu(II) coordinated with a tetravalent chelator that dictates the binding of two amphiphilic ligands in cis-orientation. Hydrophobic interactions between the lipidoids coupled with intermolecular hydrogen bonding led to a well-defined bilayer vesicle structure. Oil-soluble SNAr reaction is efficiently upregulated in the hydrophobic cavity, acting as a catalytic crucible. The modular system allows easy incorporation of exposed primary amine groups, which augments the catalysis of retro aldol and C-N bond formation reactions. Moreover, a higher-affinity chelator enables consumption of the Cu(II) template leveraging the differential thermodynamic stability, which allows a controllable lifetime of the vesicular assemblies. Concomitant temporal upregulation of the catalytic reactions could be tuned by the metal ion concentration. This work offers new possibilities for metal ion-mediated dynamic supramolecular systems, opening up a massive repertoire of functionally active dynamic "life-like" materials.

A transient vesicular glue for amplification and temporal regulation of biocatalytic reaction networks.

Regulation of enzyme activity and biocatalytic cascades on compartmentalized cellular components is key to the adaptation of cellular processes such as signal transduction and metabolism in response to varying external conditions. Synthetic molecular glues have enabled enzyme inhibition and regulation of protein-protein interactions. So far, all the molecular glue systems based on covalent interactions operated under steady-state conditions. To emulate dynamic biological processes under dissipative conditions, we introduce herein a transient supramolecular glue with a controllable lifetime. The transient system uses multivalent supramolecular interactions between guanidinium group-bearing surfactants and adenosine triphosphate (ATP), resulting in bilayer vesicle structures. Unlike the conventional chemical agents for dissipative assemblies, ATP here plays the dual role of providing a structural component for the assembly as well as presenting active functional groups to "glue" enzymes on the surface. While gluing of the enzymes on the vesicles achieves augmented catalysis, oscillation of ATP concentration allows temporal control of the catalytic activities similar to the dissipative cellular nanoreactors. We further demonstrate temporal upregulation and control of complex biocatalytic reaction networks on the vesicles. Altogether, the temporal activation of biocatalytic cascades on the dissipative vesicular glue presents an adaptable and dynamic system emulating heterogeneous cellular processes, opening up avenues for effective protocell construction and therapeutic interventions.

Metal Coordination-Driven Supramolecular Nanozyme as an Effective Colorimetric Biosensor for Neurotransmitters and Organophosphorus Pesticides.

Analytical methods for detecting neurotransmitters (NTs) and organophosphorus (OP) pesticides with high sensitivity are vitally necessary for the rapid identification of physical, mental, and neurological illnesses, as well as to ensure food safety and safeguard ecosystems. In this work, we developed a supramolecular self-assembled system (SupraZyme) that exhibits multi-enzymatic activity. SupraZyme possesses the ability to show both oxidase and peroxidase-like activity, which has been employed for biosensing. The peroxidase-like activity was used for the detection of catecholamine NTs, epinephrine (EP), and norepinephrine (NE) with a detection limit of 6.3 µM and 1.8 µM, respectively, while the oxidase-like activity was utilized for the detection of organophosphate pesticides. The detection strategy for OP chemicals was based on the inhibition of acetylcholine esterase (AChE) activity: a key enzyme that is responsible for the hydrolysis of acetylthiocholine (ATCh). The corresponding limit of detection of paraoxon-methyl (POM) and methamidophos (MAP) was measured to be 0.48 ppb and 15.8 ppb, respectively. Overall, we report an efficient supramolecular system with multiple enzyme-like activities that provide a versatile toolbox for the construction of sensing platforms for the colorimetric point-of-care detection of both NTs and OP pesticides.

Temporally Controlled Multienzyme Catalysis Using a Dissipative Supramolecular Nanozyme.

The development of superior functional enzyme mimics (nanozymes) is essential for practical applications, including point-of-care diagnostics, biotechnological applications, biofuels, and environmental remediation. Nanozymes with the ability to control their catalytic activity in response to external fuels offer functionally valuable platforms mimicking nonequilibrium systems in nature. Herein, we fabricated a supramolecular coordination bonding-based dynamic vesicle that exhibits multienzymatic activity. The supramolecular nanozyme shows effective laccase-like catalytic activity with a KM value better than the native enzyme and higher stability in harsh conditions. Besides, the nanostructure demonstrates an efficient peroxidase-like activity with NADH peroxidase-like properties. Generation of luminescence from luminol and oxidation of dopamine are efficiently catalyzed by the nanozyme with high sensitivity, which is useful for point-of-care detections. Notably, the active nanozyme exhibits dynamic laccase-mimetic activity in response to pH variation, which has never been explored before. While a neutral/high pH leads to the self-assembly, a low pH disintegrates the assembled nanostructures and consequently turns off the nanozyme activity. Altogether, the self-assembled Cu2+-based vesicular nanostructure presents a pH-fueled dissipative system demonstrating effective temporally controlled multienzymatic activity.

Optical pico-biosensing of lead using plasmonic gold nanoparticles and a cationic peptide-based aptasensor.

A novel biosensor for the rapid detection of lead ions employing the optical properties of AuNPs, a lead-specific aptamer and a cationic peptide has been demonstrated. The limit of detection of the biosensor was 98.7 pM, the lowest so far obtained using colorimetry.