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“Desolvation tips the balance: Solvent effects on aromatic interactions”
Chem. Commun.
36,
3806-8
(2006)
(cover article)
The folding behaviour of the molecular torsion balance framework is rationalised by considering the effects of solvation using the / H-bond parameter scheme for estimating the free energies of pairwise functional group interactions in solution.
“Substituent effects on aromatic stacking interactions”
Org. Biomol. Chem.
5,
1062-80
(2007)
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 CDCl3, 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 -faces of the two aromatic rings. However, electrostatic interactions between the substituents of one ring and the -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.
“Electrostatic control of aromatic stacking interactions”
J. Am. Chem. Soc.
127,
8594-5
(2005)
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.
“Chemical double-mutant cycles: Dissecting non-covalent interactions”
Chem. Soc. Rev.
36,
172-88
(2007)
Thermodynamic double-mutant cycles and triple-mutant boxes are widely employed for the experimental quantification of non-covalent interactions and cooperative effects in proteins. This review describes the application of these powerful methodologies to the study of non-covalent interactions in synthetic systems.
“Modular multi-level circuits from immobilized DNA-based logic gates”
J. Am. Chem. Soc.
129,
14875-9
(2007)
Featured in:
Nature
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.
“Experimental Measurement of Noncovalent Interactions between Halogens & Aromatic Rings”
ChemBioChem
5,
657-65
(2004)
Chemical double mutant cycles have been used to quantify the interactions of halogens with the faces of aromatic rings in chloroform. The halogens are forced over the face of an aromatic ring by an array of hydrogen-bonding interactions that lock the complexes in a single, well-defined conformation. These interactions can also be engineered into the crystal structures of simpler model compounds, but experiments in solution show that the halogen- aromatic interactions observed in the solid state are all unfavourable, regardless of whether the aromatic rings contain electron-withdrawing or electron- donating substituents. The halogen-aromatic interactions are repulsive by 1-3 kJ mol-1. The interactions with fluorine are slightly less favourable than with chlorine and bromine.
“A single-molecule nanopore device detects DNA polymerase activity with single-nucleotide resolution”
J. Am. Chem. Soc.
130,
818-20
(2008)
Featured in:
Nature |
Nature Nanotechnology |
ACS Chemical Biology
The ability to monitor DNA polymerase activity with single-nucleotide resolution has been the cornerstone of a number of advanced single-molecule DNA sequencing concepts. Toward this goal, we report the first observation of the base-by-base DNA polymerase activity with single-base resolution at the single-molecule level. We describe the design and characterization of a supramolecular nanopore device capable of detecting up to nine consecutive DNA polymerase-catalyzed single-nucleotide primer extensions with high sensitivity and spatial resolution (2.4 Å). The device is assembled in a suspended lipid membrane by threading and mechanically capturing a single strand of DNA-PEG copolymer inside an -hemolysin protein pore. Single-nucleotide primer extensions result in successive displacements of the template DNA strand within the protein pore, which can be monitored by the corresponding stepped changes in the ion current flowing through the pore under an applied transmembrane potential. The system described thus represents a promising advance toward nanopore-mediated single-molecule DNA sequencing concept and, in addition, might be applicable to studying a number of other biopolymer-protein interactions and dynamics.