Axial chirality is a prevalent and important phenomenon in chemistry. Herein we report a combination of dynamic covalent chemistry and axial chirality for the development of a versatile platform for the binding and chirality sensing of multiple classes of mononucleophiles. An equilibrium between an open aldehyde and its cyclic hemiaminal within biphenyl derivatives enabled the dynamic incorporation of a broad range of alcohols, thiols, primary amines, and secondary amines with high efficiency. Selectivity toward different classes of nucleophiles was also achieved by regulating the distinct reactivity of the system with external stimuli. Through induced helicity as a result of central-to-axial chirality transfer, the handedness and ee values of chiral monoalcohol and monoamine analytes were reported by circular dichroism. The strategies introduced herein should find application in many contexts, including assembly, sensing, and labeling.

Orbital donor–acceptor interactions play critical roles throughout chemistry, and hence, their regulation and functionalization are of great significance. Herein we demonstrate for the first time the investigation of n→π* interactions through the strategy of dynamic covalent chemistry (DCC), and we further showcase its use in the stabilization of imine. The n→π* interaction between donor X and acceptor aldehyde/imine within 2-X-2′-formylbiphenyl derivatives was found to significantly influence the thermodynamics of imine exchange. The orbital interaction was then quantified through imine exchange, the equilibrium of which was successfully correlated with the difference in natural bond orbital stabilization energy of n→π* interactions of aldehyde and its imine. Moreover, the examination of solvent effects provided insights into the distinct feature of the modulation of n→π* interaction with aprotic and protic solvents. The n→π* interaction involving imine was enhanced in protic solvents due to hydrogen bonding with the solvent. This finding further enabled the stabilization of imine in purely aqueous solution. The strategies and results reported should find application in many fields, including molecular recognition, biological labeling, and asymmetric catalysis.

Lanthanide (Ln(3+))-doped nanoparticles (NPs) are an intensive area of research in chemical and materials sciences. Herein a sensor array of Ln(3+)-doped NPs was developed for the first time toward sensitive molecular sensing based on a novel strategy of the hybridized time-resolved Förster resonance energy transfer (TR-FRET) with the indicator displacement assay (IDA) concept (TR-FRET-IDA). The sensor platform was generated in situ by binding a series of negatively charged indicators on the surface of ligand-free LiYF4:Ce/Tb NPs. The TR-FRET between NPs and dyes resulted in indicator emission and was employed as a means of removing undesired short-lived background luminescence from the indicator effectively. Displacement of indicators from the NP/indicator ensembles by glyphosate, a common herbicide, led to turn-off of the indicator emission. The sensor array was able to successfully discriminate 11 biologically relevant anions with high accuracy and sensitivity in pure aqueous buffer both qualitatively and quantitatively. Furthermore, the differentiation of six model proteins in the nM range was achieved with 100% accuracy for the classification, thereby demonstrating the versatility of this simple sensor platform. The study of the mechanism of binding and signal modulation further verified TR-FRET-IDA as a reliable sensing paradigm.

The role of n → π* orbital interactions in the rotational pathway and barrier of biaryl-based molecular rotors was elucidated through a combined experimental and computational study. The n → π* interaction in the transition state can lead to the acceleration of rotors. The competition between the n → π* interaction and hydrogen bonding further enabled the reversal of the pathway and greasing/braking the rotor in response to acid/base stimuli, thereby creating a switchable molecular rotor.

Molecular switches are an intensive area of research, and in particular, the control of multistate switching is challenging. Herein we introduce a general and versatile strategy of dynamic covalent switches and communicating networks, wherein distinct states of reversible covalent systems can induce addressable fluorescence switching. The regulation of intramolecular ring/chain equilibrium, intermolecular dynamic covalent reactions (DCRs) with amines, and both permitted the activation of optical switches. The variation in electronwithdrawing competition between the fluorophore and 2formylbenzenesulfonyl unit afforded diverse signaling patterns. The combination of switches in situ further enabled the creation of communicating networks for multistate color switching, including white emission, through the delicate control of DCRs in complex mixtures. Finally, reversible and recyclable multiresponsive luminescent materials were achieved with molecular networks on the solid support, allowing visualization of different types of vapors and quantification of primary amine vapors with high sensitivity and wide detection range. The results reported herein should be appealing for future studies of dynamic assemblies, molecular sensing, intelligent materials, and biological labeling.

Achieving complexity is central to the creation of chemical systems, inspired by natural systems. Herein we introduce a strategy of switchable orthogonal dynamic covalent chemistry (DCC) toward the regulation of complex dynamic networks. The control of dual reactivity of tautomers and resulting pathways allowed reversible covalent bonding of a large scope of primary amines, secondary amines, alcohols, and thiols with high efficiency. The selection of reaction pathways next enabled the realization of orthogonal but switchable dynamic covalent reactions (DCRs) with nucleophile pairs of amine/alcohol, alcohol/thiol, and amine/thiol by varying protonation and oxidation states. Control experiments confirmed the crucial role of dual reactivity on the stability and switchability of DCRs. The specificity toward amines, alcohols, and thiols, as well as interconversion between their corresponding assemblies, was further accomplished in one vessel, thus creating tunable communicating networks with three types of DCRs. Moreover, the switchable orthogonality combined with differential reactivity of multiple sulfonamides and nucleophiles enhanced the complexity within dynamic libraries. The generality and versatility of our approaches should facilitate their incorporation into many aspects of chemistry endeavors.

Dynamic covalent chemistry (DCC) has become a powerful tool for the creation of molecular assemblies and complex systems in chemistry and materials science. Herein we developed for the first time quantitative reactivity scales capable of correlation and prediction of the equilibrium of dynamic covalent reactions (DCRs). The reference reactions are based upon universal DCRs between imines, one of the most utilized structural motifs in DCC, and a series of O-, N-, and S- mononucleophiles. Aromatic imines derived from pyridine-2-carboxyaldehyde exhibit capability for controlling the equilibrium through distinct substituent effects. Electron-donating groups (EDGs) stabilize the imine through quinoidal resonance, while electron-withdrawing groups (EWGs) stabilize the adduct by enhancing intramolecular hydrogen bonding, resulting in curvature in Hammett analysis. Notably, unique nonlinearity induced by both EDGs and EWGs emerged in Hammett plot when cyclic secondary amines were used. This is the first time such a behavior is observed in a thermodynamically controlled system, to the best of our knowledge. Unified quantitative reactivity scales were proposed for DCC and defined by the correlation log K = S(N) (R(N) + R(E)). Nucleophilicity parameters (R(N) and S(N)) and electrophilicity parameters (R(E)) were then developed from DCRs discovered. Furthermore, the predictive power of those parameters was verified by successful correlation of other DCRs, validating our reactivity scales as a general and useful tool for the evaluation and modeling of DCRs. The reactivity parameters proposed here should be complementary to well-established kinetics based parameters and find applications in many aspects, such as DCR discovery, bioconjugation, and catalysis.

A versatile strategy of n → π* interactions was developed for tunable control of dynamic imine chemistry and the regulation of imine formation/exchange in water.