Shapeshifting Molecules
Lead Research Organisation:
Durham University
Department Name: Chemistry
Abstract
Different sequences of atoms give molecules with distinct shapes. This shape is key to a molecule's properties, e.g., its biological effect when binding proteins. Conventionally, the atomic sequence of a molecule is fixed. This proposal, however, investigates molecules that break free from this dogma. 'Shapeshifting' molecules adapt their atomic sequences to match their surroundings.
During this Early Career Fellowship, the project team and I will establish methods to control shapeshifting molecules. We will pioneer their applications in catalysis, drugs, and plastics. We expect to discover rare properties, such as plastics made from molecular networks that spontaneously tangle and untangle, making them uniquely strong and flexible. We will also answer open questions about how shapeshifting molecules adapt when they interact with other molecules, quantifying changes in their structures. This knowledge will allow us to make shapeshifting molecules that mould themselves to match complex biological targets implicated in disease.
By the end of the grant, we will have shown how shapeshifting molecules differ from conventional materials. We will have also demonstrated the first of their many possible applications in biology and soft materials. These fundamental, chemical advances establish a new research area that will have broad impacts in biochemistry, materials physics and engineering.
During this Early Career Fellowship, the project team and I will establish methods to control shapeshifting molecules. We will pioneer their applications in catalysis, drugs, and plastics. We expect to discover rare properties, such as plastics made from molecular networks that spontaneously tangle and untangle, making them uniquely strong and flexible. We will also answer open questions about how shapeshifting molecules adapt when they interact with other molecules, quantifying changes in their structures. This knowledge will allow us to make shapeshifting molecules that mould themselves to match complex biological targets implicated in disease.
By the end of the grant, we will have shown how shapeshifting molecules differ from conventional materials. We will have also demonstrated the first of their many possible applications in biology and soft materials. These fundamental, chemical advances establish a new research area that will have broad impacts in biochemistry, materials physics and engineering.
People |
ORCID iD |
Paul McGonigal (Principal Investigator / Fellow) |
Description | When a carbon atom forms four bonds to different groups, the molecule can exist in two mirror image forms. These mirror image forms are vital in medicine because they have different biological activities. Usually, it is impossible to interconvert between these 'enantiomers' because to do so would require a bond to be broken, a process that needs too much energy. Our team demonstrated that if the chiral centre was part of a dynamic molecular cage structure, then a simple rearrangement of the cage could lead to inversion of the mirror image form of the molecule. In this way, carbon-based stereochemistry, which is normally considered to be fixed and rigid, became dynamic, fluxional and responsive - a new paradigm in carbon-centred chirality. |
Exploitation Route | In due course this intriguing bonding concept may be found to apply in other contexts, such as in the interaction of small-molecules to the chiral binding pockets of proteins, and potentially used to underpin new applications for more dynamic molecular materials. |
Sectors | Chemicals Pharmaceuticals and Medical Biotechnology |
Description | Fluxionality-Induced Enantiomerisation in Ligand Design |
Amount | £1,740,139 (GBP) |
Funding ID | EP/Z00036X/1 |
Organisation | Engineering and Physical Sciences Research Council (EPSRC) |
Sector | Public |
Country | United Kingdom |
Start | 09/2024 |
End | 09/2029 |
Title | CCDC 2068012: Experimental Crystal Structure Determination |
Description | Related Article: Aisha Bismillah, Toby Johnson, Burhan Hussein, Andrew Turley, Ho Chi Wong, Juan Aguilar, Dmitry Yufit, Paul McGonigal|2022|ResearchSq.|||doi:10.21203/rs.3.rs-318491/v1 |
Type Of Material | Database/Collection of data |
Year Produced | 2022 |
Provided To Others? | Yes |
URL | http://www.ccdc.cam.ac.uk/services/structure_request?id=doi:10.5517/ccdc.csd.cc27dy2p&sid=DataCite |
Title | CCDC 2068013: Experimental Crystal Structure Determination |
Description | Related Article: Aisha Bismillah, Toby Johnson, Burhan Hussein, Andrew Turley, Ho Chi Wong, Juan Aguilar, Dmitry Yufit, Paul McGonigal|2022|ResearchSq.|||doi:10.21203/rs.3.rs-318491/v1 |
Type Of Material | Database/Collection of data |
Year Produced | 2022 |
Provided To Others? | Yes |
URL | http://www.ccdc.cam.ac.uk/services/structure_request?id=doi:10.5517/ccdc.csd.cc27dy3q&sid=DataCite |
Title | CCDC 2068014: Experimental Crystal Structure Determination |
Description | Related Article: Aisha Bismillah, Toby Johnson, Burhan Hussein, Andrew Turley, Ho Chi Wong, Juan Aguilar, Dmitry Yufit, Paul McGonigal|2022|ResearchSq.|||doi:10.21203/rs.3.rs-318491/v1 |
Type Of Material | Database/Collection of data |
Year Produced | 2022 |
Provided To Others? | Yes |
URL | http://www.ccdc.cam.ac.uk/services/structure_request?id=doi:10.5517/ccdc.csd.cc27dy4r&sid=DataCite |
Title | CCDC 2068015: Experimental Crystal Structure Determination |
Description | Related Article: Aisha Bismillah, Toby Johnson, Burhan Hussein, Andrew Turley, Ho Chi Wong, Juan Aguilar, Dmitry Yufit, Paul McGonigal|2022|ResearchSq.|||doi:10.21203/rs.3.rs-318491/v1 |
Type Of Material | Database/Collection of data |
Year Produced | 2022 |
Provided To Others? | Yes |
URL | http://www.ccdc.cam.ac.uk/services/structure_request?id=doi:10.5517/ccdc.csd.cc27dy5s&sid=DataCite |
Title | CCDC 2068016: Experimental Crystal Structure Determination |
Description | Related Article: Aisha Bismillah, Toby Johnson, Burhan Hussein, Andrew Turley, Ho Chi Wong, Juan Aguilar, Dmitry Yufit, Paul McGonigal|2022|ResearchSq.|||doi:10.21203/rs.3.rs-318491/v1 |
Type Of Material | Database/Collection of data |
Year Produced | 2022 |
Provided To Others? | Yes |
URL | http://www.ccdc.cam.ac.uk/services/structure_request?id=doi:10.5517/ccdc.csd.cc27dy6t&sid=DataCite |
Title | CCDC 2068017: Experimental Crystal Structure Determination |
Description | Related Article: Aisha Bismillah, Toby Johnson, Burhan Hussein, Andrew Turley, Ho Chi Wong, Juan Aguilar, Dmitry Yufit, Paul McGonigal|2022|ResearchSq.|||doi:10.21203/rs.3.rs-318491/v1 |
Type Of Material | Database/Collection of data |
Year Produced | 2022 |
Provided To Others? | Yes |
URL | http://www.ccdc.cam.ac.uk/services/structure_request?id=doi:10.5517/ccdc.csd.cc27dy7v&sid=DataCite |
Title | CCDC 2068018: Experimental Crystal Structure Determination |
Description | Related Article: Aisha Bismillah, Toby Johnson, Burhan Hussein, Andrew Turley, Ho Chi Wong, Juan Aguilar, Dmitry Yufit, Paul McGonigal|2022|ResearchSq.|||doi:10.21203/rs.3.rs-318491/v1 |
Type Of Material | Database/Collection of data |
Year Produced | 2022 |
Provided To Others? | Yes |
URL | http://www.ccdc.cam.ac.uk/services/structure_request?id=doi:10.5517/ccdc.csd.cc27dy8w&sid=DataCite |
Title | CCDC 2068019: Experimental Crystal Structure Determination |
Description | Related Article: Aisha Bismillah, Toby Johnson, Burhan Hussein, Andrew Turley, Ho Chi Wong, Juan Aguilar, Dmitry Yufit, Paul McGonigal|2022|ResearchSq.|||doi:10.21203/rs.3.rs-318491/v1 |
Type Of Material | Database/Collection of data |
Year Produced | 2022 |
Provided To Others? | Yes |
URL | http://www.ccdc.cam.ac.uk/services/structure_request?id=doi:10.5517/ccdc.csd.cc27dy9x&sid=DataCite |
Title | CCDC 2068020: Experimental Crystal Structure Determination |
Description | Related Article: Aisha Bismillah, Toby Johnson, Burhan Hussein, Andrew Turley, Ho Chi Wong, Juan Aguilar, Dmitry Yufit, Paul McGonigal|2022|ResearchSq.|||doi:10.21203/rs.3.rs-318491/v1 |
Type Of Material | Database/Collection of data |
Year Produced | 2022 |
Provided To Others? | Yes |
URL | http://www.ccdc.cam.ac.uk/services/structure_request?id=doi:10.5517/ccdc.csd.cc27dyby&sid=DataCite |
Title | CCDC 2173984: Experimental Crystal Structure Determination |
Description | Related Article: Aisha N. Bismillah, Tobias G. Johnson, Burhan A. Hussein, Andrew T. Turley, Ho Chi Wong, Juan A. Aguilar, Dmitry S. Yufit, Paul R. McGonigal|2023|Nature Chemistry|15|615|doi:10.1038/s41557-023-01156-7 |
Type Of Material | Database/Collection of data |
Year Produced | 2023 |
Provided To Others? | Yes |
URL | http://www.ccdc.cam.ac.uk/services/structure_request?id=doi:10.5517/ccdc.csd.cc2bz6j2&sid=DataCite |