Functionalised nanopores: chemical and biological modifications

Nanopore technology has established itself as a powerful tool for single-molecule studies. By analysing changes in the ion current flowing through a single transmembrane channel, a wealth of molecular information can be elucidated. Early studies utilised nanopore technology for sensing applications, and subsequent developments have diversified its remit. Nanopores can be synthetic, solid-state, or biological in origin, but recent work has seen these boundaries blurred as hybrid functionalised pores emerge. The modification of existing pores and the construction of novel synthetic pores has been an enticing goal for creating systems with tailored properties and functionality. Here, we explore chemically functionalised biological pores and the bio-inspired functionalisation of solid-state pores, highlighting how the convergence of these domains provides enhanced functionality.

The convergence of chemistry, biology, and solid-state approaches enables the construction hybrid nanopores with enhanced single-molecule applications.     

Electrostatic control of aromatic stacking interactions

A supramolecular approach has been used to investigate the free energies of intermolecular aromatic stacking interactions. Chemical double mutant cycles have been used to measure the effect of a range of substituents on face-to-face stacking interactions with phenyl and pentafluorophenyl rings. Electrostatic effects dominate the trends in interaction energy.     

Desolvation tips the balance: solvent effects on aromatic interactions

The folding behaviour of the molecular torsion balance framework is rationalised by considering the effects of solvation using the alpha/beta H-bond parameter scheme for estimating the free energies of pairwise functional group interactions in solution.     

Substituent effects on aromatic stacking interactions

Synthetic supramolecular zipper complexes have been used to quantify substituent effects on the free energies of aromatic stacking interactions. The conformational properties of the complexes have been characterised using NMR spectroscopy in CDCl(3), and by comparison with the solid state structures of model compounds. The structural similarity of the complexes makes it possible to apply the double mutant cycle method to evaluate the magnitudes of 24 different aromatic stacking interactions. The major trends in the interaction energy can be rationalised using a simple model based on electrostatic interactions between the pi-faces of the two aromatic rings. However, electrostatic interactions between the substituents of one ring and the pi-face of the other make an additional contribution, due to the slight offset in the stacking geometry. This property makes aromatic stacking interactions particularly sensitive to changes in orientation as well as the nature and location of substituents.     

The Energetic Significance of Metallophilic Interactions

Metallophilic interactions are increasingly recognized as playing an important role in molecular assembly, catalysis, and bio‐imaging. However, present knowledge of these interactions is largely derived from solid‐state structures and gas‐phase computational studies rather than quantitative experimental measurements. Here, we have experimentally quantified the role of aurophilic (Au^I???Au^I), platinophilic (Pt^II???Pt^II), palladophilic (Pd^II???Pd^II), and nickelophilic (Ni^II???Ni^II) interactions in self‐association and ligand‐exchange processes. All of these metallophilic interactions were found to be too weak to be well‐expressed in several solvents. Computational energy decomposition analyses supported the experimental finding that metallophilic interactions are overall weak, meaning that favorable dispersion and orbital hybridization contributions from M???M binding are largely outcompeted by electrostatic or dispersion interactions involving ligand or solvent molecules. This combined experimental and computational study provides a general understanding of metallophilic interactions and indicates that great care must be taken to avoid over‐attributing the energetic significance of metallophilic interactions.     

The Importance of 1,5-Oxygen⋅⋅⋅Chalcogen Interactions in Enantioselective Isochalcogenourea Catalysis

The importance of 1,5-O⋅⋅⋅chalcogen (Ch) interactions in isochalcogenourea catalysis (Ch=O, S, Se) is investigated. Conformational analyses of N-acyl isochalcogenouronium species and comparison with kinetic data demonstrate the significance of 1,5-O⋅⋅⋅Ch interactions in enantioselective catalysis. Importantly, the selenium analogue demonstrates enhanced rate and selectivity profiles across a range of reaction processes including nitronate conjugate addition and formal [4+2] cycloadditions. A gram-scale synthesis of the most active selenium analogue was developed using a previously unreported seleno-Hugerschoff reaction, allowing the challenging kinetic resolutions of tertiary alcohols to be performed at 500 ppm catalyst loading. Density functional theory (DFT) and natural bond orbital (NBO) calculations support the role of orbital delocalization (occurring by intramolecular chalcogen bonding) in determining the conformation, equilibrium population, and reactivity of N-acylated intermediates.     

Can Dispersion Forces Govern Aromatic Stacking in an Organic Solvent?

Experimental support for the dominance of van der Waals dispersion forces in aromatic stacking interactions occurring in organic solution is surprisingly limited. The size‐dependence of aromatic stacking in an organic solvent was examined. The interaction energy was found to vary by about 7.5 kJ mol^?1 on going from a phenyl–phenyl to an anthracene–pyrene stack. Strikingly, the experimental data were highly correlated with dispersion energies determined using symmetry‐adapted perturbation theory (SAPT), while the induction, exchange, electrostatic, and solvation energy components correlated poorly. Both the experimental data and the SAPT‐dispersion energies gave high‐quality correlations with the change in solvent accessible area upon complexation. Thus, the size‐dependence of aromatic stacking interactions is consistent with the dominance of van der Waals dispersion forces even in the presence of a competing polarizable solvent.     

The Importance of 1,5‐Oxygen⋅⋅⋅Chalcogen Interactions in Enantioselective Isochalcogenourea Catalysis

The importance of 1,5‐O???chalcogen (Ch) interactions in isochalcogenourea catalysis (Ch=O, S, Se) is investigated. Conformational analyses of N‐acyl isochalcogenouronium species and comparison with kinetic data demonstrate the significance of 1,5‐O???Ch interactions in enantioselective catalysis. Importantly, the selenium analogue demonstrates enhanced rate and selectivity profiles across a range of reaction processes including nitronate conjugate addition and formal [4+2] cycloadditions. A gram‐scale synthesis of the most active selenium analogue was developed using a previously unreported seleno‐Hugerschoff reaction, allowing the challenging kinetic resolutions of tertiary alcohols to be performed at 500 ppm catalyst loading. Density functional theory (DFT) and natural bond orbital (NBO) calculations support the role of orbital delocalization (occurring by intramolecular chalcogen bonding) in determining the conformation, equilibrium population, and reactivity of N‐acylated intermediates.     

Modular multi-level circuits from immobilized DNA-based logic gates

One of the fundamental goals of molecular computing is to reproduce the tenets of digital logic, such as component modularity and hierarchical circuit design. An important step toward this goal is the creation of molecular logic gates that can be rationally wired into multi-level circuits. Here we report the design and functional characterization of a complete set of modular DNA-based Boolean logic gates (AND, OR, and AND-NOT) and further demonstrate their wiring into a three-level circuit that exhibits Boolean XOR (exclusive OR) function. The approach is based on solid-supported DNA logic gates that are designed to operate with single-stranded DNA inputs and outputs. Since the solution-phase serves as the communication medium between gates, circuit wiring can be achieved by designating the DNA output of one gate as the input to another. Solid-supported logic gates provide enhanced gate modularity versus solution-phase systems by significantly simplifying the task of choosing appropriate DNA input and output sequences used in the construction of multi-level circuits. The molecular logic gates and circuits reported here were characterized by coupling DNA outputs to a single-input REPORT gate and monitoring the resulting fluorescent output signals.