Bond Formation Studies By Charge Density Measurements and Solid State 17O NMR Spectrometry
Lead Research Organisation:
Nottingham Trent University
Department Name: School of Science & Technology
Abstract
This project concerns the formation of chemical bonds. The reactions chosen are addition reactions of electron-rich groups such as amines or those containing negatively charged oxygen atoms with electron-poor groups such as carbon-carbon double bonds which have electron attracting groups attached. Molecules will be prepared which have a pair of such groups held in close proximity. The degree of bond formation between them will be detected by measurements of the electron density between them, and by nuclear magnetic resonances (NMR) measurements on powdered crystalline samples - detecting either the nitrogen (as 15N) or oxygen (as 17O) atom of the electron-rich group. These measurements are at the cutting edge of both these techniques. The electron density distribution on a particular molecule is determined from very accurate X-ray diffraction measurements (XRD) on a small crystal, and this will contribute to the growing use of this technique internationally to examine weak bonding interactions. Of particular importance is to determine how the properties of the electron density distribution between the reacting groups changes as the distance between the groups decreases i.e. as the bond forms. Use of NMR measurements on powdered crystalline samples means that the solid state structure determined by X-ray diffraction, can be directly related to the position of the signal from N or O in the NMR experiment. The NMR measurements using 17O will be ground breaking, since this has only become feasible through recent developments of the technique, including double rotation of the sample in the magnetic field. Nevertheless, for the 17O measurements it will be necessary to prepare compounds which are enriched in the 17O isotope. Finally, and of particular importance, the choice of cation accompanying the oxygen anion will be varied to determine how this alters the reactivity of the oxygen anion, which will be monitored by structural (XRD) and NMR measurements building on earlier results. The reactivity of the oxygen would be expected to be decreased by cations which bind more tightly to it, and our measurements will provide an approach to quantify this.
Publications
Rees G
(2021)
Mapping of N-C Bond Formation from a Series of Crystalline Peri-Substituted Naphthalenes by Charge Density and Solid-State NMR Methodologies
in Angewandte Chemie
Rees GJ
(2021)
Mapping of N-C Bond Formation from a Series of Crystalline Peri-Substituted Naphthalenes by Charge Density and Solid-State NMR Methodologies.
in Angewandte Chemie (International ed. in English)
Rees GJ
(2020)
Measuring multiple 17O-13C J-couplings in naphthalaldehydic acid: a combined solid state NMR and density functional theory approach.
in Physical chemistry chemical physics : PCCP
Lari A
(2012)
Models for incomplete nucleophilic attack on a protonated carbonyl group and electron-deficient alkenes: salts and zwitterions from 1-dimethylamino-naphthalene-8-carbaldehyde.
in Organic & biomolecular chemistry
Lari A
(2011)
The use of the triptycene framework for observing O?C?O molecular interactions
in CrystEngComm
Description | The interaction between a dimethylamino nitrogen atom and the carbon atom of an aldehyde or polarised alkene where the N--C distance lies in the range 1.61-2.67 Angstroms have been examined by topological analysis of the charge density (measured by X-ray diffraction) and by the coupling between these two (isotopically labelled as 15N and 13C) atoms in their solid-state NMR spectra, to study the process of N-C bond formation. The second derivative of the electron density at the bond critical poin |
Exploitation Route | This work contributes to the understanding of interactions between functional groups which is of importance to the pharmaceutical industry in the design of drugs to fit macromolecular sites. The potential of this work is to stimulate the use of charge density and solid state NMR in the study of bond formation, a central process in chemistry. |
Sectors | Chemicals Pharmaceuticals and Medical Biotechnology |
Description | Bond formation is a critical process in chemistry and biology. This work shows for the first time how both charge density measurements and solid state NMR can be used to monitor the degree of bond formation between and nitrogen and a carbon atom. This provides a great stimulus for the investigation of new systems. The project has demonstrated the use of two techniques which can be used on crystalline materials for probing the degree of bond formation between two functional groups which lie c |
First Year Of Impact | 2011 |
Sector | Cultural |
Description | Nottingham Trent/Southampton/Warwick Collaboration |
Organisation | University of Southampton |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | The collaboration between the groups at Nottingham Trent University (organic synthesis and structural measurement), Southampton University (charge density measurement) and Warwick University (solid-state NMR) was greatly strengthened by the project supported by this grant. This led on to new work on salts formed from peri-naphthalenes, whose results will be published soon. The National Crystallography Service (EPSRC) located at Southampton are expert in charge density measurements and the the solid-state NMR group at Warwick are internationally recognised for their work. |
Collaborator Contribution | Warwick: solid-state NMR measurements on compounds, some doubly isotopically labelled, whose crystal structures we have unambiguously determined, allowing the Warwick group to apply complementary calculations of NMR parameters. Southampton: charge density measurements from accurate X-ray diffraction data on compounds with interactions between particular pairs of functional groups |
Impact | N. Mercadal S.P. Day A. Jarmyn, M.B. Pitak, S.J. Coles, C.Wilson, G.J. Rees, J.V. Hanna J.D. Wallis, "O- v N- Protonation of 1-Dimethylaminonaphthalene-8-ketones: Formation of an N-C Bond or a Hydrogen Bond to the Pi-Electron Density of a Carbonyl Group", CrystEngComm, 2014, 16, 8363 - 8374, DOI:10.1039/c4ce00981a. G. J. Rees, S.P. Day, A. Lari, A. P. Howes, D. Iuga, M.B. Pitak, S.J. Coles, T.L. Threlfall, M. E. Light, M. E. Smith, J.D. Wallis, J.V. Hanna, "A Multi-Nuclear Solid State NMR, Density Functional Theory and X-Ray Diffraction Study of Hydrogen Bonding in Group I Hydrogen Dibenzoates", CrystEngComm (special crystallography and NMR issue), 2013, 15, 8823-8839, DOI: 10.1039/C3CE41258J. A. Lari, M.B. Pitak, S.J. Coles, G.J. Rees, S.P. Day, M.E. Smith?, J.V. Hanna, J.D. Wallis, "Models for Incomplete Nucleophilic Attack on a Protonated Carbonyl Group and Electron-Deficient Alkenes: Salts and Zwitterions from Peri-Substituted 1-Dimethylamino-naphthalenes", Org. Biomolec. Chem., 2012, 10, 7763-79. |
Start Year | 2007 |
Description | Nottingham Trent/Southampton/Warwick Collaboration |
Organisation | University of Warwick |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | The collaboration between the groups at Nottingham Trent University (organic synthesis and structural measurement), Southampton University (charge density measurement) and Warwick University (solid-state NMR) was greatly strengthened by the project supported by this grant. This led on to new work on salts formed from peri-naphthalenes, whose results will be published soon. The National Crystallography Service (EPSRC) located at Southampton are expert in charge density measurements and the the solid-state NMR group at Warwick are internationally recognised for their work. |
Collaborator Contribution | Warwick: solid-state NMR measurements on compounds, some doubly isotopically labelled, whose crystal structures we have unambiguously determined, allowing the Warwick group to apply complementary calculations of NMR parameters. Southampton: charge density measurements from accurate X-ray diffraction data on compounds with interactions between particular pairs of functional groups |
Impact | N. Mercadal S.P. Day A. Jarmyn, M.B. Pitak, S.J. Coles, C.Wilson, G.J. Rees, J.V. Hanna J.D. Wallis, "O- v N- Protonation of 1-Dimethylaminonaphthalene-8-ketones: Formation of an N-C Bond or a Hydrogen Bond to the Pi-Electron Density of a Carbonyl Group", CrystEngComm, 2014, 16, 8363 - 8374, DOI:10.1039/c4ce00981a. G. J. Rees, S.P. Day, A. Lari, A. P. Howes, D. Iuga, M.B. Pitak, S.J. Coles, T.L. Threlfall, M. E. Light, M. E. Smith, J.D. Wallis, J.V. Hanna, "A Multi-Nuclear Solid State NMR, Density Functional Theory and X-Ray Diffraction Study of Hydrogen Bonding in Group I Hydrogen Dibenzoates", CrystEngComm (special crystallography and NMR issue), 2013, 15, 8823-8839, DOI: 10.1039/C3CE41258J. A. Lari, M.B. Pitak, S.J. Coles, G.J. Rees, S.P. Day, M.E. Smith?, J.V. Hanna, J.D. Wallis, "Models for Incomplete Nucleophilic Attack on a Protonated Carbonyl Group and Electron-Deficient Alkenes: Salts and Zwitterions from Peri-Substituted 1-Dimethylamino-naphthalenes", Org. Biomolec. Chem., 2012, 10, 7763-79. |
Start Year | 2007 |
Description | Invited speaker, IUPAC 44th World Chemistry Congress, 2013 |
Form Of Engagement Activity | Scientific meeting (conference/symposium etc.) |
Part Of Official Scheme? | Yes |
Type Of Presentation | keynote/invited speaker |
Geographic Reach | International |
Primary Audience | Other academic audiences (collaborators, peers etc.) |
Results and Impact | The talk led to interesting discussions with other participants. I visited a laboratory at Istanbul Technical University. |
Year(s) Of Engagement Activity | 2013 |
Description | Probing Chemical Bond Formation and Interactions |
Form Of Engagement Activity | Scientific meeting (conference/symposium etc.) |
Part Of Official Scheme? | No |
Type Of Presentation | poster presentation |
Geographic Reach | International |
Primary Audience | Other academic audiences (collaborators, peers etc.) |
Results and Impact | A poster presented at the European Charge Density Meeting (ECD6) in ?trbsk? Pleso, Slovakia in Sept 2012 by Dr Mateusz Pitak, demonstrating how the careful topological analysis of high quality X-ray diffraction data can be used to characterise interactions and partially formed bonds between a dimethylamino group and various electrophilic centres in the peri-positions of a naphthalene ring. The value of the second derivative of the electron density at the bond critical point is shown to be sensit Other experts in the field came to discuss the work described in the poster. |
Year(s) Of Engagement Activity | 2012 |
Description | RSC Midlands Organic Chemistry Meeting, 2013, Nottingham Trent University |
Form Of Engagement Activity | Scientific meeting (conference/symposium etc.) |
Part Of Official Scheme? | No |
Type Of Presentation | poster presentation |
Geographic Reach | Regional |
Primary Audience | Postgraduate students |
Results and Impact | Poster presentation of results concerning the mapping of bond formation by charge density studies. The use of charge density measurements for monitoring bond formation were presented in poster form to an audience of PhD students, academics and some industrial representatives. Informal discussions of the work at the poster. |
Year(s) Of Engagement Activity | 2013 |
Description | Zwitterions and Salts with Long N-C Bonds from Peri-Naphthalenes: Structures, Charge Density Measurements and Solid State NMR Studies. |
Form Of Engagement Activity | Scientific meeting (conference/symposium etc.) |
Part Of Official Scheme? | No |
Type Of Presentation | paper presentation |
Geographic Reach | International |
Primary Audience | Other academic audiences (collaborators, peers etc.) |
Results and Impact | A talk at the IUPAC International Conference on Physical Organic Chemistry, Durham University, Sept 2012, to present the most important results obtained through this grant, showing how an incompletely formed N-C chemical bond can be characterised (a) by charge density measurements by X-ray diffraction and its topological analysis and (b) solid-state NMR measurements, in particular the coupling through the studied bond between isotopically labelled atoms (15N and 13C). The main results from A number of informal discussions on the work undertaken. |
Year(s) Of Engagement Activity | 2012 |