Characterisation of organic solids using solid-state NMR spectroscopy

This thesis utilizes high-resolution solid-state magic angle spinning (MAS) NMR technique for the characterisation of various organic compounds, specifically pharmaceutical APIs, mesoporous silica loaded with iPMPA, and solid electrolyte interphase layer (SEI) components of lithium-ion batteries. Solid-state NMR is highly sensitive to the local environment, and hence MAS experiments in particular two-dimensional experiments can be used to probe 1H ̶1H and 1H ̶X (X=7Li, 13C, 14N, 29Si, 31P) proximities. Some of the presented results have used an NMR crystallography approach, whereby chemical shifts are calculated using the gauge-including projector augmented wave (GIPAW) method for structures usually obtained from diffraction. Moreover, intermolecular hydrogen bonding motifs can be probed by a comparison of chemical shifts calculated for the full crystal to those calculated chemical shift for an isolated molecule. The first application concerns conformational polymorphism, which is the existence in distinct solid-state forms of the same molecule in different conformations due to variation in torsion angle and has importance for the development of pharmaceutical products. 1H− 1H homonuclear and 13C− 1H and 14N− 1H heteronuclear correlation solid-state NMR approaches are used to elucidate crystal packing and internuclear proximities between nuclei. This Chapter considers the development of a scoring function for evaluating crystal structures of tolfenamic acid (TFA) using solution- and solid-state NMR data. To build this scoring function, we experimentally measured (Form I and Form II) and calculated (Form I, II, III, and IV) 1H and 13C chemical shifts in both the solid state and in solution. The implementation of solid-state NMR chemical shift data in conjunction with both experimental and calculated changes in solution NMR chemical shifts allowed the scoring function to discriminate amongst four similar TFA polymorphs. This approach has the potential to improve the efficiency and accuracy of crystal structure prediction (CSP) by incorporating solution-state NMR conformational and chemical shift data into solid-state NMR based NMR crystallography approaches. Importantly, this novel approach provides a way to predict the conformation of a new polymorphic form for which experimental NMR data is accessible but there is no crystal structure. In a second application, a range of isopropyl methyl (iPMPA, a degradation product of the chemical warfare agent Sarin) loaded mesoporous silica samples are investigated through multinuclear solid-state NMR. 13C cross polarisation (CP) MAS NMR spectra confirmed the presence of iPMPA molecules in the silica matrix. 1H, 31P, and two-dimensional heteronuclear experiments are applied to probe the number of phosphorous sites and hydrogen bonding motifs. xvi Variable-temperature 1H and 31P MAS NMR experiments provided information about the mobility of acidic protons involved in hydrogen bonding. A structural model for the iPMPA loading in the pores of the mesoporous silica is presented. In a third application, a series of standard components of an solid-electrolyte interphase (SEI) layer along with the SEI generated on graphite electrode was investigated using fast MAS NMR. Specifically, high-resolution 1H, 7Li, 1H-1H DQ/MAS, 7Li-1H HMQC, and 13C CP MAS techniques are used, in conjunction with GIPAW calculated NMR chemical shifts to provide an understanding about likely components in the SEI layer. Specifically, a solid-state NMR characterisation of lithium ethylene dicarbonate (LEDC) and lithium mono carbonate (LMC) is presented

Elucidation of microbial lignin degradation pathways using synthetic isotope-labelled lignin

Pathways by which the biopolymer lignin is broken down by soil microbes could be used to engineer new biocatalytic routes from lignin to renewable chemicals, but are currently not fully understood. In order to probe these pathways, we have prepared synthetic lignins containing 13C at the sidechain β-carbon. Feeding of [β-13C]-labelled DHP lignin to Rhodococcus jostii RHA1 has led to the incorporation of 13C label into metabolites oxalic acid, 4-hydroxyphenylacetic acid, and 4-hydroxy-3-methoxyphenylacetic acid, confirming that they are derived from lignin breakdown. We have identified a glycolate oxidase enzyme in Rhodococcus jostii RHA1 which is able to oxidise glycolaldehyde via glycolic acid to oxalic acid, thereby identifying a pathway for the formation of oxalic acid. R. jostii glycolate oxidase also catalyses the conversion of 4-hydroxyphenylacetic acid to 4-hydroxybenzoylformic acid, identifying another possible pathway to 4-hydroxybenzoylformic acid. Formation of labelled oxalic acid was also observed from [β-13C]-polyferulic acid, which provides experimental evidence in favour of a radical mechanism for α,β-bond cleavage of β-aryl ether units

Identifying the components of the solid–electrolyte interphase in Li-ion batteries

The importance of the solid–electrolyte interphase (SEI) for reversible operation of Li-ion batteries has been well established, but the understanding of its chemistry remains incomplete. The current consensus on the identity of the major organic SEI component is that it consists of lithium ethylene di-carbonate (LEDC), which is thought to have high Li-ion conductivity, but low electronic conductivity (to protect the Li/C electrode). Here, we report on the synthesis and structural and spectroscopic characterizations of authentic LEDC and lithium ethylene mono-carbonate (LEMC). Direct comparisons of the SEI grown on graphite anodes suggest that LEMC, instead of LEDC, is likely to be the major SEI component. Single-crystal X-ray diffraction studies on LEMC and lithium methyl carbonate (LMC) reveal unusual layered structures and Li+ coordination environments. LEMC has Li+ conductivities of >1 × 10−6 S cm−1, while LEDC is almost an ionic insulator. The complex interconversions and equilibria of LMC, LEMC and LEDC in dimethyl sulfoxide solutions are also investigated

Conformations in solution and in solid-state polymorphs : correlating experimental and calculated NMR chemical shifts for Tolfenamic acid

A new approach for quantitively assessing putative crystal structures with applications in crystal structure prediction (CSP) is introduced that is based upon experimental solution- and magic-angle spinning (MAS) solid-state NMR data and density functional theory (DFT) calculation. For the specific case of tolfenamic acid (TFA), we consider experimental solution-state NMR for a range of solvents, experimental MAS NMR of polymorphs I and II, and DFT calculations for four polymorphs. The change in NMR chemical shift observed in passing from the solution state to the solid state (ΔδExperimental) is calculated as the difference between 1H and 13C experimental solid-state chemical shifts for each polymorphic form (δSolid expt) and the corresponding solution-state NMR chemical shifts (δSolution expt). Separately, we use the gauge-included projector augmented wave (GIPAW) method to calculate the NMR chemical shifts for each form (δSolid calc) and for TFA in solution (δSolution calc), using the dynamic 3D solution conformational ensemble determined from NMR spectroscopy. The calculated change in passing from the solution state to the solid state, ΔδCalculated, is then calculated as the difference of δSolid calc and δSolution calc. Regression analysis for ΔδCalculated against ΔδExperimental followed by a t-test for statistical significance provides a robust quantitative assessment. We show that this assessment clearly identifies the correct polymorph, i.e., when comparing ΔδExperimental based on the experimental MAS NMR chemical shifts of Form I or II with ΔδCalculated based on calculated chemical shifts for polymorphs I, II, III and IV. Complementarity to the established approach of comparing δSolid expt to δSolid calc is explored. We further show that our approach is applicable if there are no solid-state crystal structure data. Specifically, δSolid calc in ΔδCalculated is replaced by the chemical shift for an isolated molecule with a specific conformation. Sampling conformations at specific 15° angle values and comparing them against experimental 13C chemical shift data for Forms I and II identifies matching narrow ranges of conformations, successfully predicting the conformation of tolfenamic acid in each form. This methodology can therefore be used in crystal structure prediction to both reduce the initial conformational search space and also quantitatively assess subsequent putative structures to reliably and unambiguously identify the correct structure

Data for Conformations in solution and in solid-state polymorphs : correlating experimental and calculated NMR chemical shifts for Tolfenamic acid

A new approach for quantitively assessing putative crystal structures with applications in crystal structure prediction (CSP) is introduced that is based upon experimental solution- and magic-angle spinning (MAS) solid-state NMR data and density functional theory (DFT) calculation. For the specific case of tolfenamic acid (TFA), we consider experimental solution-state NMR for a range of solvents, experimental MAS NMR of polymorphs I and II, and DFT calculations for four polymorphs. The change in NMR chemical shift observed in passing from the solution state to the solid state (ΔδExperimental) is calculated as the difference between 1H and 13C experimental solid-state chemical shifts for each polymorphic form (δSolid expt) and the corresponding solution-state NMR chemical shifts (δSolution expt). Separately, we use the gauge-included projector augmented wave (GIPAW) method to calculate the NMR chemical shifts for each form (δSolid calc) and for TFA in solution (δSolution calc), using the dynamic 3D solution conformational ensemble determined from NMR spectroscopy. The calculated change in passing from the solution state to the solid state, ΔδCalculated, is then calculated as the difference of δSolid calc and δSolution calc. Regression analysis for ΔδCalculated against ΔδExperimental followed by a t-test for statistical significance provides a robust quantitative assessment. We show that this assessment clearly identifies the correct polymorph, i.e., when comparing ΔδExperimental based on the experimental MAS NMR chemical shifts of Form I or II with ΔδCalculated based on calculated chemical shifts for polymorphs I, II, III and IV. Complementarity to the established approach of comparing δSolid expt to δSolid calc is explored. We further show that our approach is applicable if there are no solid-state crystal structure data. Specifically, δSolid calc in ΔδCalculated is replaced by the chemical shift for an isolated molecule with a specific conformation. Sampling conformations at specific 15° angle values and comparing them against experimental 13C chemical shift data for Forms I and II identifies matching narrow ranges of conformations, successfully predicting the conformation of tolfenamic acid in each form. This methodology can therefore be used in crystal structure prediction to both reduce the initial conformational search space and also quantitatively assess subsequent putative structures to reliably and unambiguously identify the correct structure

Data for Identifying the components of the solid–electrolyte interphase in Li-ion Batteries

The importance of the solid–electrolyte interphase (SEI) for reversible operation of Li-ion batteries has been well established, but the understanding of its chemistry remains incomplete. The current consensus on the identity of the major organic SEI component is that it consists of lithium ethylene di-carbonate (LEDC), which is thought to have high Li-ion conductivity, but low electronic conductivity (to protect the Li/C electrode). Here, we report on the synthesis and structural and spectroscopic characterizations of authentic LEDC and lithium ethylene mono-carbonate (LEMC). Direct comparisons of the SEI grown on graphite anodes suggest that LEMC, instead of LEDC, is likely to be the major SEI component. Single-crystal X-ray diffraction studies on LEMC and lithium methyl carbonate (LMC) reveal unusual layered structures and Li+ coordination environments. LEMC has Li+ conductivities of >1 × 10−6 S cm−1, while LEDC is almost an ionic insulator. The complex interconversions and equilibria of LMC, LEMC and LEDC in dimethyl sulfoxide solutions are also investigated