The MJH research group are based in the Johnson Laboratory (Bedson Building) in the School of Natural and Environmental Sciences, Newcastle University.

We are an organic chemistry research group working in a number of areas of organic chemistry and chemical biology, including:

  • (1) the development of new synthetic methodology
  • (2) the isolation and synthesis of novel small molecule antibiotics
  • (3) the synthesis of functional fluorophores for biological imaging
  • (4) the development of high throughput methods in X-ray crystallography

 


Research Highlights

Encapsulated Nanodroplet Crystallisation of Organic Soluble Small Molecules (ENaCt)

Working with Drs Probert and Heaps (NCL), Prof Steed (Durham) and Dr Thaw (SPT Labtech), we have developed a general method for the high-throughput nanoscale crystallisation of organic-soluble small molecules, Encapsulated Nanodroplet Crystallisation (ENaCt). ENaCt provides crystals suitable for X-ray analysis, allowing structural and de novo absolute stereochemical assignment for a diverse and challenging range of small molecules (bioactives, natural products, organometallics etc.) as well as acting as a tool for new polymorph discovery.

 

Natural Product Antibiotics from Actinomycetes 

Actinomycetes are bacteria rich in bioactive natural products, many of which show antibiotic properties. Working in collaboration with a microbiology team we are interested in the isolation, structural solution and bioactivity investigation of new antibiotic natural products.

Figure thumbnail fx1

 

Chiral BODIPY Fluorophores

The synthesis and resolution of a class of chiral organic fluorophores, axially chiral 4,4-difluoro-4-bora-3a,4a-diaza-s-indacenes (Ax*-BODIPY), is described. Ax*-BODIPYs were prepared through a modular synthesis combined with a late stage Heck functionalisation. Resolution was achieved by preparative chiral HPLC. Absolute stereochemical assignment was performed by comparison of experimental ECD spectra with TD-DFT calculations.

Graphical abstract: Axially chiral BODIPYs

 

Grignard Reagents as Reducing Agents

2,2,2-Trichloro-1-arylethanones undergo high yielding reductions to the corresponding 2,2-dichloro-1-arylethanones in the presence of RMgX. A single electron transfer mechanism for the reaction is proposed based on trapping experiments. Reaction of the intermediate enolates with a range of electrophiles is described, providing a convenient route to substituted α,α-dichloro-β-hydroxyketones and related molecules.

Graphical abstract: Reduction of 2,2,2-trichloro-1-arylethanones by RMgX: mechanistic investigation and the synthesis of substituted α,α-dichloroketones

 


Research Funding

2020

IIIP PhD Scholarship

2019

Northern Accelerator Executive into Business

Northern Accelerator CCF (PoC): Robot Assisted Micro-crystallisation Platform for Polymorph Screening and Structural Solution – Prototype Workflow Development, Industrial Demonstrations and Market Development, £48,683

MICA: Novel mode of RNA polymerase inhibition by a new natural rifamycin, which is active against rifampicin-resistant RNA polymerase, Medical Research Council (MRC), £603,841

Industrial Demonstration of Newcastle High Throughput Crystallisation Screening Platform, Higher Education Innovation Fund (HEIF), £11,845

High throughput structural elucidation of plant natural products and agrochemical metabolites, N8 Research Partnership, £31,580

2018

Metabolomics by Automated Crystallography (MbAC): Solving the Structural Elucidation Bottleneck in Natural Product Discovery and Bioengineering through Automated Crystallisation and Single Crystal X-Ray Diffraction, NPRONET, Biotechnology and Biological Sciences Research Council (BBSRC), £43,843

2017

Bill toScale-up and Structural Elucidation of Novel Natural Product Antibiotics from the Demuris Actinomycete Collection, NPRONET, Biotechnology and Biological Sciences Research Council (BBSRC), £10,000

2016

Studying the development of a new natural product antibiotic for the treatment of ESKAPE infections, Rosetrees Trust, £54,171

2014

A New Antibiotic for Gram Positive Bacterial Infections, Medical Research Council (MRC), £29,282

2013

A Novel Crosslinking Strategy for MS Structural Biology, Biotechnology and Biological Sciences Research Council (BBSRC), £116,056

2012

Probing the Mechanisms of dSTORM Reporters, Biotechnology and Biological Sciences Research Council (BBSRC), £118,521

2010

Towards commercial application of a novel method to prevent and remove bacterial biofilms, Natural Environment Research Council (NERC), £137,802

Diels-Alder/Ene Reactions for the Multi-Component Synthesis, Engineering and Physical Sciences Research Council (EPSRC), £96,013

Total: £1,301,637