John Wallis

Research areas

The Wallis group has research activity in the areas of organic conductors and superconductors derived from organosulfur donors, the study of bond formation between functional groups by studies on molecules with partially formed bonds, and in aspects of heterocyclic chemistry. The group is also involved in medicinally related projects, in particular related to cancer. There are excellent facilities for synthetic chemistry and X-ray crystallography. He welcomes applications from potential PhD students. The most recent completed PhD theses are from students who came from Libya, Italy and UK.

• Organic Conductors

A wide range of new substituted derivatives of the organosulfur donor BEDT-TTF have been prepared. Hydroxyl, amino and carboxyl derivatised materials provide both hydrogen bonding for organising the crystalline state, and also the potential for attachment of new molecular systems bringing new properties. Multi-substituted donors have been prepared, and a new strategy has been developed for providing such materials as one stereoisomer.

This has laid the foundation for a more crystal engineering approach to the design of conducting organic systems. The success in the synthesis has allowed the preparation of donors functionalised with metal binding groups which are being used for incorporation of magnetic metal ions to study the interplay of electrical and magnetic properties. The diastereoselective cycloaddition of a dithione to enantiopure alkenes has opened up access to enantiopure donors, so that the influence of chirality on electro-magnetic properties can now also be investigated. He collaborates extensively with colleague Dr Lee Martin.

The application of novel BEDT-TTF derivatives in molecular electronics, e.g. as components of transistors, is being explored.

• Bond Formation Studies

The research group studies the formation of partial bonds between functional groups by measuring the X-ray structures of molecules in which those groups are forced close to one another, for example in peri-naphthalene systems. Accurate charge density measurements analysed by the “Atoms in Molecules” approach are used to study the stages of bond formation between the reacting groups, e.g. an amine and an electrophilic alkene, which are also complemented by solid state NMR measurements on the crystal studied. The interactions of oxyanions with electrophilic centres is a current area of study.

Intermolecular interactions have been modelled by the structures of 2,2’-disubstituted biphenyl systems, where the groups are free to move apart due to the free rotation about the central bond. This provides an alternative approach for those interactions which do not commonly occur in the Cambridge Structural Database.

• Medicinal Chemistry

Collaboration with health scientists are directed at new anti-metastatic cancer agents and other therapies. The interdisciplinary approach combines computer aided design, synthesis of targets and biological testing.

Applications of reactive species such as cyclic sulfate esters and electron deficient alkynes to preparing heterocyclic compounds will be extended to the preparation of new libraries of compounds for biological testing.

Opportunities to carry out postgraduate research towards an MPhil/PhD exist in the areas of organic materials chemistry, organic chemistry and studies of molecular interactions and further information may be obtained from the NTU Graduate School.

PhD projects available:

Design of Novel Beta-blockers for the Retardation of Breast Cancer Metastasis.

Collaboration with Dr Amanda Miles, Dr Carl Nelson, Dr Chris Garner.

Epidemiological studies have shown a significant association between β-blocker usage and improved breast cancer patient outcome. These studies found that patients with triple negative breast cancer (TNBC) benefitted the most from simultaneous intake of β-blockers. The rationale for using novel β₂-selective β-blockers as a therapy for basal TNBC derives from their capacity to inhibit catecholamine-induced activation of G protein-coupled β₂-adrenoceptors that drive cancer cell signalling pathways and cancer cell migration. Additional data obtained from pre-clinical and epidemiological studies has led to the hypothesis that β₂-selective blockers are key mediators in preventing BC progression, rather than the β₁-selective or β₁/β₂ non-selective counterparts. A panel of novel small molecules have recently been developed between Dr Amanda Miles (Jon van Geest Centre, NTU) and the synthetic chemistry laboratory of Prof John Wallis and Dr Chris Garner (Department of Chemistry and Forensics, NTU). Current work demonstrates that one of these novel compounds is able to significantly reduce the migration and invasion of breast cancer cells in vitro. We would now like to: (i) further investigate the novel compound’s biological effects and pharmacological profile (in collaboration with Dr Carl Nelson); (ii) investigate the metabolism and pharmacokinetic dynamics of the novel compound; before (iii) identifying its clinical utility in vivo. Furthermore, the synthetic chemistry component of the project is ongoing and concerns the preparation and purification of more of the most biologically active materials, as well as extending the family of drug candidates by making small molecular changes to the molecular structure of the lead. This interdisciplinary approach encompasses the range of skills needed in modern day drug development including computer aided drug design, chemical synthesis, receptor binding studies and subsequent biological testing of the compounds.

Mapping the process of bond formation by computation, synthesis and crystallography.

Dr Matt Addicoat, Prof. John Wallis.

When is a chemical bond actually formed? As two atoms approach each other, they reach a point where their electrons are shared between both atoms – a chemical bond. What we don’t know is where that point actually is, and what occurs either side of the “bond-forming transition state”. Understanding when and how two atoms share electrons to form a bond has important implications for the design of catalysts and the understanding of enzymes (Nature’s catalysts). In this project we will use computational crystal structure prediction to identify a series of molecules that have a range of constrained N---C separations. These molecules will then be synthesized and high-resolution X-ray crystallography will be used to determine the distribution of electrons in the N---C “bond” as it forms and ultimately show us the process of chemical bond formation.

Synthesis of 3,3’-Substituted Bipyridines with C-H Activation.

Dr Warren Cross and Prof. John Wallis

2,2’-Bipyridines used in extensively in coordination chemistry, and have applications in OLEDS, metal-organic frameworks and metal waste recovery.  However, there are no good routes to the 3,3’-disubstituted derivatives, but substituents in these positions have potential for installing small twists in the ligands and also offer least hindrance to systems with several bipyridines around a metal ion.  In this project we will develop a method for a catalytic C-H activation route to such materials, with the metal catalyst being coordinated at one pyridine ring and activating the 3-C-H on the other ring. Installation of two electrophilic groups into the bipyridine also offer substances for the study of N---electrophile interactions, and so this is a very interesting family of materials, which currently are not accessible.  The project will be supervised by Dr Warren Cross and Prof John Wallis

Organic Superconductors, Molecular Switches and Chiral Conductivity.

Dr Lee Martin, Prof John Wallis

This project concerns the application of BEDT-TTF derived organosulfur donors in the preparation of novel electroactive charge transfer salts, with applications in molecular electronics. This builds upon the recent achievement of a new superconductor and a new, near room temperature, electrical molecular switch from these materials. The project will involve organic synthesis of new donors including enantiopure ones, formation of charge transfer salts and characterisation of the structural and electrical properties of their salts, in some cases with novel complex magnetic anions.  The project will involve collaboration with Japanese research groups.