π-Stacking is central to a variety of pursuits in chemistry and its modulation mechanism is complicated. In this manuscript, a strategy that bridges the research of dynamic covalent chemistry and weak interactions, as a means of developing simple, general, and versatile systems for the regulation of π-stacking, is demonstrated. The dynamic covalent assembly allows easy access to structural diversity by varying amine components and facile quantification of substituent effects of π-stacking with in situ competing π-stacking systems in the form of amine exchange. The π-stacking of chiral amines within the adduct enables chirality induction from homotopic faces. For more information see the Communication by L. You et al. on page 3804 ff.

AbstractHerein we report for the first time the use of dynamic covalent reactions (DCRs) for building a π-stacking model system and further quantifying its substituent effects (SEs), which remain a topic of debate despite the rich history of stacking. A general DCR between 10-methylacridinium ion and primary amines was discovered, in which π-stacking played a stabilizing role. Facile quantification of SEs with in situ competing π-stacking systems was next achieved in the form of amine exchange exhibiting structural diversity by simply varying components. The linear correlation with σm in Hammett plots indicates the dominance of purely electrostatic SEs, and the additivity of SEs is in line with the direct interaction model. With α-chiral amines π-stacking within the adduct enabled chirality transfer from homotopic faces. The strategy of dynamic covalent assembly should be appealing to future research of probing weak interactions and manipulating chirality.

The use of dynamic assembly for molecular sensing is an intensive area of research in supramolecular chemistry. However, the development of self-assembly architectures for the detection of multiple signals remains challenging. Here, we present dynamic covalent assemblies with multiresponsive properties that also show unique selectivity profiles in water. The receptors were generated in a single step with modularly designed building blocks through acylhydrazone linkages, and their orthogonal assembly with a series of external stimuli was investigated. Notably, the system exhibits responses toward cations, anions, solvents, pH, and amphiphilicity. The discrimination of Cu2+ from other divalent metal ions was achieved by simply changing the solvent and was evidenced by a Cu2+-induced pKa shift. The selective recognition of CN– in pure aqueous media was also accomplished through a cooperative effect in conjunction with Zn2+. Furthermore, the assembly and its responsiveness are functional both in solution and the solid state. The aggregation ability of these dynamic covalent systems supports their binding and sensing properties.Keywords: cooperative binding; dynamic assembly; molecular recognition; sensors; supramolecular chemistry

Lanthanide (Ln3+)-doped nanoparticles (NPs) are an intensive area of research in chemical and materials sciences. Herein a sensor array of Ln3+-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.Keywords: FRET; indicator displacement assay; lanthanide; nanoparticles; sensor array

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 = SN (RN + RE). Nucleophilicity parameters (RN and SN) and electrophilicity parameters (RE) 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.

The research of systems chemistry exploring complex mixtures of interacting synthetic molecules has been burgeoning recently. Herein we demonstrate for the first time the coupling of molecular switches with a dynamic covalent reaction (DCR) and the modulation of created chemical cascades with a variety of inputs, thus closely mimicking a biological signaling system. A novel Michael type DCR of 10-methylacridinium perchlorate and monothiols exhibiting excellent regioselectivity and tunable affinity was discovered. A delicate balance between the unique reactivity of the reactant and the stability of the adduct leads to the generation of a strong acid in a thermodynamically controlled system. The dynamic cascade was next created via coupling of the DCR and a protonation-induced configurational switch (E/Z isomerization) through a proton relay. Detailed examination of the interdependence of the equilibrium enabled us to rationally optimize the cascade and also shed light on the possible intermediate of the switching process. Furthermore, relative independence of the coupled reactions was verified by the identification of stimuli that are able to facilitate one reaction but suppress the other. To further enhance systematic complexity, a second DCR of electrophilic aldehydes and thiols was employed for the reversible inhibition of the binary system, thus achieving the interplay of multiple equilibria. Finally, a fluorescence switch was turned on through coupling with the DCR, showcasing the versatility of our strategy. The results described herein should pave the way for the exploitation of multifunctional dynamic covalent cascades.

In an effort to develop reactivity-based dynamic covalent bonding and to expand the scope and application of the dynamic covalent chemistry, in situ-generated simple generic iminium ions were utilized for the dynamic covalent binding of monoalcohols with high affinity. Hammett analysis was conducted to manipulate the equilibrium and correlate with the reactivity of reactants. The structural features of aldehydes and secondary amines were identified, and both polar and steric effects have significant impact on the binding. In particular, the substrates which can participate in π–π and polar−π interactions are able to afford apparent equilibrium constants in the magnitude of 104 M–2, demonstrating the power of weak supramolecular forces to stabilize the dynamic covalent assembly. The generality of the assembly was validated with a series of mono secondary alcohols. To showcase the practicality of our system, chirality discrimination and ee measurement of chiral secondary alcohols were achieved.

The recognition and analysis of mono-functionalized organics is an intensive area of research in organic chemistry. Toward this end, an in situ-generated metal-templated dynamic multi-component covalent assembly for the reversible binding and chirality sensing of mono secondary amines is presented. The reaction of pyridine-2-carboxyaldhyde, di(2-picolyl)amine, zinc triflate, tetrabutylammonium chloride, and a series of secondary amines, affords tripodal aminal zinc complexes. The dynamic nature of the system was demonstrated by component exchange of both amines and aldehydes. The equilibrium can be modulated by changing counteranions, concentrations, as well as structural feature of the amines. The competition between two iminium pathways resulted in a unique distribution of components. Due to the enantiotopicity of iminiums, decent diastereoselectivity was observed for chiral secondary amines. The resulting diastereomeric helical complexes were employed for the determination of enantiomeric excess with high accuracy.