Co-reporter:R. Li;R. Rajan;W. C. V. Wong;D. G. Reid;M. J. Duer;V. J. Somovilla;N. Martinez-Saez;G. J. L. Bernardes;R. Hayward;C. M. Shanahan
Chemical Communications 2017 vol. 53(Issue 100) pp:13316-13319
Publication Date(Web):2017/12/14
DOI:10.1039/C7CC06624D
Non-enzymatic glycation of extracellular matrix with (U-13C5)-D-ribose-5-phosphate (R5P), enables in situ 2D ssNMR identification of many deleterious protein modifications and crosslinks, including previously unreported oxalamido and hemiaminal (CH3–CH(OH)NHR) substructures. Changes in charged residue proportions and distribution may be as important as crosslinking in provoking and understanding harmful tissue changes.
Co-reporter:Chris J. Pickard;Erika Davies;Jeremy N. Skepper;David G. Reid;Karin H. Müller;Wai Ching Wong
PNAS 2014 Volume 111 (Issue 14 ) pp:E1354-E1363
Publication Date(Web):2014-04-08
DOI:10.1073/pnas.1315080111
We provide evidence that citrate anions bridge between mineral platelets in bone and hypothesize that their presence acts
to maintain separate platelets with disordered regions between them rather than gradual transformations into larger, more
ordered blocks of mineral. To assess this hypothesis, we take as a model for a citrate bridging between layers of calcium
phosphate mineral a double salt octacalcium phosphate citrate (OCP-citrate). We use a combination of multinuclear solid-state
NMR spectroscopy, powder X-ray diffraction, and first principles electronic structure calculations to propose a quantitative
structure for this material, in which citrate anions reside in a hydrated layer, bridging between apatitic layers. To assess
the relevance of such a structure in native bone mineral, we present for the first time, to our knowledge, 17O NMR data on bone and compare them with 17O NMR data for OCP-citrate and other calcium phosphate minerals relevant to bone. The proposed structural model that we deduce
from this work for bone mineral is a layered structure with thin apatitic platelets sandwiched between OCP-citrate–like hydrated
layers. Such a structure can explain a number of known structural features of bone mineral: the thin, plate-like morphology
of mature bone mineral crystals, the presence of significant quantities of strongly bound water molecules, and the relatively
high concentration of hydrogen phosphate as well as the maintenance of a disordered region between mineral platelets.
Co-reporter:David G. Reid;Karin H. Muller;Rakesh Rajan;Roger A. Brooks;W. Ying Chow;Maggie Green;Dominique Bihan;Wai Ching Wong;Jeremy N. Skepper;David A. Slatter;Catherine M. Shanahan;Richard W. Farndale
Science 2014 Volume 344(Issue 6185) pp:742-746
Publication Date(Web):16 May 2014
DOI:10.1126/science.1248167
Fundamentals of Bone Formation
In vitro models can help guide research for tissue engineering or drug delivery, but the extent to which results from in vitro experiments may mimic in vivo ones will depend on the robustness of the model. For complex tissues like the extracellular matrix or bone, this means matching the chemical organization of the tissue at both the atomic scale and the structural level. Chow et al. (p. 742) used nuclear magnetic resonance (NMR) spectroscopy to analyze a sample on both these length scales. First an isotope-enriched mouse was produced to enhance the NMR signal. Samples from these mice were then used to study the extracellular matrix of developing bone and the calcification front during fetal bone growth.
Co-reporter:David G. Reid;Graham E. Jackson
Calcified Tissue International 2013 Volume 93( Issue 3) pp:253-260
Publication Date(Web):2013 September
DOI:10.1007/s00223-013-9751-5
There is continuing debate about whether abundant citrate plays an active role in biomineralization of bone. Using solid state NMR dipolar dephasing, we examined another normally mineralized hard tissue, mineralized articular cartilage, as well as biocalcifications arising in pathological conditions, mineralized intimal atherosclerotic vascular plaque, and apatitic uroliths (urinary stones). Residual nondephasing 13C NMR signal at 76 ppm in the spectra of mineralized cartilage and vascular plaque indicates that a quaternary carbon atom resonates at this frequency, consistent with the presence of citrate. The presence, and as yet unproven possible mechanistic involvement, of citrate in tissue mineralization extends the compositional, structural, biogenetic, and cytological similarities between these tissues and bone itself. Out of 10 apatitic kidney stones, five contained NMR-detectable citrate. Finding citrate in a high proportion of uroliths may be significant in view of the use of citrate in urolithiasis therapy and prophylaxis. Citrate may be essential for normal biomineralization (e.g., of cartilage), play a modulatory role in vascular calcification which could be a target for therapeutic intervention, and drive the formation of apatitic rather than other calcific uroliths, including more therapeutically intractable forms of calcium phosphate.
Co-reporter:Erika Davies ; Melinda J. Duer ; Sharon E. Ashbrook ;John M. Griffin
Journal of the American Chemical Society 2012 Volume 134(Issue 30) pp:12508-12515
Publication Date(Web):June 29, 2012
DOI:10.1021/ja3017544
By combining X-ray crystallography, first-principles density functional theory calculations, and solid-state nuclear magnetic resonance spectroscopy, we have refined the crystal structure of octacalcium phosphate (OCP), reassigned its 31P NMR spectrum, and identified an extended hydrogen-bonding network that we propose is critical to the structural stability of OCP. Analogous water networks may be related to the critical role of the hydration state in determining the mechanical properties of bone, as OCP has long been proposed as a precursor phase in bone mineral formation. The approach that we have taken in this paper is broadly applicable to the characterization of crystalline materials in general, but particularly to those incorporating hydrogen that cannot be fully characterized using diffraction techniques.
Co-reporter:Wing Ying Chow;Adam M. Taylor;David G. Reid;Melinda J. Duer;James A. Gallagher
Journal of Inherited Metabolic Disease 2011 Volume 34( Issue 6) pp:1137-1140
Publication Date(Web):2011/12/01
DOI:10.1007/s10545-011-9373-x
In pilot studies of the usefulness of solid state nuclear magnetic resonance spectroscopy in characterizing chemical and molecular structural effects of alkaptonuria on connective tissue, we have obtained 13 C spectra from articular cartilage from an AKU patient. An apparently normal anatomical location yielded a cross polarization magic angle spinning spectrum resembling literature spectra and dominated by collagen and glycosaminoglycan signals. All spectral linewidths from strongly pigmented ochronotic cartilage however were considerably increased relative to the control indicating a marked increase in collagen molecular disorder. This disordering of cartilage structural protein parallels, at the atomic level, the disordering revealed at higher length scales by microscopy. We also demonstrate that the abnormal spectra from ochronotic cartilage fit with the abnormality in the structure of collagen fibres at the ultrastructural level, whereby large ochronotic deposits appear to alter the structure of the collagen fibre by invasion and cross linking. Summary: Increased signal linewidths in solid state NMR spectra of ochronotic articular cartilage from an AKU patient relative to linewidths in normal, control, cartilage reveals a marked decrease in collagen molecular order in the diseased tissue. This atomic level disordering parallels higher length scale disorder revealed by microscopic techniques.
Co-reporter:Joanna V. Bradley, Lydia N. Bridgland, Dawn E. Colyer, Melinda J. Duer, Tomislav Friščić, James R. Gallagher, David G. Reid, Jeremy N. Skepper, and Christine M. Trasler
Chemistry of Materials 2010 Volume 22(Issue 22) pp:6109
Publication Date(Web):October 21, 2010
DOI:10.1021/cm101730f
Nanoparticulate hydroxyapatites (HAps) reproducing some of the subnanometre length scale intermolecular interactions characteristic of hard tissue have been prepared for nuclear magnetic resonance (NMR) structural elucidation. HAps were precipitated at physiological pH and temperature from dilute aqueous solutions, in the presence of acidic polysaccharides (chondroitin sulfate, dermatan sulfate, hyaluronic acid, dextran sulfate, polygalacturonic acid), and of hydrophilic poly aminoacids (poly-l-glutamate, poly-l-asparagine, poly-l-lysine). The HAp resembles that of bone with respect to its 31P NMR properties, broad reflections in X-ray powder diffraction, and the coexistence of an ordered crystalline core, surrounded by a less ordered surface containing water and hydrogen phosphate. 13C{31P} rotational echo double resonance (REDOR) NMR, which probes carbon−phosphorus proximities below ca. 1 nm, shows that all the HAps are molecular composites in which each biopolymer forms intimate intermolecular associations with mineral ions. REDOR effects between mineral phosphorus and ring carbons of the polysaccharides, and the side-chain terminal carboxylate and amide carbonyls of poly-l-glutamate and poly-l-asparagine, and the side chain carbons of poly-l-lysine, closely recapitulate those seen in native bone. Such model HAp−biopolymer composites will prove useful in studies of the role of biopolymers in biomineralization, and in high resolution biomineral structure elucidation.
Co-reporter:David G. Reid, Melinda J. Duer, Rachel C. Murray and Erica R. Wise
Chemistry of Materials 2008 Volume 20(Issue 11) pp:3549
Publication Date(Web):May 9, 2008
DOI:10.1021/cm800514u
Co-reporter:M. S. Ironside;D. G. Reid ;M. J. Duer
Magnetic Resonance in Chemistry 2008 Volume 46( Issue 10) pp:913-917
Publication Date(Web):
DOI:10.1002/mrc.2262
Abstract
Powder patterns and sideband patterns have different strengths when it comes to using them to determine chemical shift parameters. Here, we show that chemical shift parameters can be determined with high accuracy by analysing the correlation pattern from a 2D experiment which correlates a powder pattern in the indirect dimension with a sideband pattern in the direct dimension. The chemical shift parameters so determined have greater accuracy than those obtained by analysing a sideband or powder pattern alone, for the same signal-to-noise ratio. This method can be applied for both resolved correlation patterns and to cases where two components share similar isotropic chemical shifts. The methodology is demonstrated in this paper, both theoretically and experimentally, on the 31P signals of the bis-phosphonate drug, pamidronate. Copyright © 2008 John Wiley & Sons, Ltd.
Co-reporter:Serena M. Best;David G. Reid;Erica R. Wise;Shuo Zou
Magnetic Resonance in Chemistry 2008 Volume 46( Issue 4) pp:323-329
Publication Date(Web):
DOI:10.1002/mrc.2168
Abstract
We have synthesised three materials–chondroitin sulphate (ChS, a commercial product derived from shark cartilage and predominantly chondroitin-6-sulphate (Ch-6-S)) bound to pre-formed hydroxyapatite (HA, Ca10(PO4)6(OH)2), HA formed in the presence of ChS and poly-Asp bound to pre-formed HA–to generate models for the mineral–organic interface in bone. The three materials have been investigated by 13C cross polarisation magic-angle spinning (CPMAS) NMR, 13C{31P} rotational echo double resonance (REDOR) and powder x-ray diffraction (XRD) in order to verify their composition and to determine the nature of their binding to HA. Our results show that for HA formed in the presence of Ch-6-S, all carbon atoms in the Ch-6-S having contact with mineral phosphate. We propose that HA in this case forms all around the Ch-6-S polymer rather than along one face of it as is more commonly supposed in cases of templating by organic molecules. However, Ch-6-S binding to pre-formed HA probably occurs via a surface layer of water on the mineral rather than to the mineral directly. In contrast, poly-Asp binds closely to the pre-formed HA surface and so is clearly able to displace at least some of the surface-bound water. Copyright © 2008 John Wiley & Sons, Ltd.
Co-reporter:Robin M. Orr, Melinda J. Duer, Sharon E. Ashbrook
Journal of Magnetic Resonance 2005 Volume 174(Issue 2) pp:301-309
Publication Date(Web):June 2005
DOI:10.1016/j.jmr.2005.03.001
An experiment is presented that enables the measurement of small chemical shift anisotropy tensors under fast magic-angle spinning (MAS). The two-dimensional spectra obtained give a fast MAS sideband pattern in the directly observed dimension with the spinning sideband intensities equivalent to the chemical shift anisotropy scaled by a factor of N, or equivalently the sample spinning frequency scaled by 1/N, in the indirectly observed dimension. The scaling factor may be arbitrarily varied by changing the number and timings of the rotor synchronized π-pulses used. Desirable features of the experiment include a fixed length pulse sequence and efficient sampling of the indirectly observed dimension. In addition, neither quadrature detection in the indirect dimension nor storage periods are required, consequently no signal intensity is discarded by the pulse sequence. The experiment is demonstrated using 31P NMR of sodium phosphate and 13C NMR of fumaric acid monoethyl ester for which a scaling factor of N = 10.2 was employed.
Co-reporter:Melinda J. Duer and Caroline Roper
Physical Chemistry Chemical Physics 2003 vol. 5(Issue 14) pp:3034-3041
Publication Date(Web):18 Jun 2003
DOI:10.1039/B303475P
The origin of the odd–even effect in the solid–nematic phase transition temperatures for a series of molecules is investigated by a variety of solid-state NMR experiments and powder XRD. The molecules consist of a flexible alkyl chain –(CH2)n–, with identical aromatic mesogenic groups at either end. It is found that the alkyl chain in the molecules exists in a range of different conformations in the solid state. The different conformations are in exchange with each other at room temperature and above. Molecules with n odd show a greater range of conformations at any given temperature than those with n even. The conformational distributions in the nematic phases is investigated by quenching samples from the nematic phase to low temperature. It is found that the range of conformations available to the alkyl chains in the nematic phase is similar to that in the solid state at room temperature. The molecular packing in the solid state is investigated by powder XRD and by studying the molecular dynamics of both the alkyl chains and the mesogenic groups by solid-state NMR. It is concluded that compounds with n odd have significantly different packing from those with n even. This in turn accounts for the different range of alkyl chain conformations seen in the n odd and n even compounds, and at least in part explains the odd–even effect in the solid–nematic phase transition temperatures seen along the series of molecules.
Co-reporter:Melinda J. Duer, Nicky McDougal and Rachel C. Murray
Physical Chemistry Chemical Physics 2003 vol. 5(Issue 13) pp:2894-2899
Publication Date(Web):03 Jun 2003
DOI:10.1039/B302506C
A solid-state NMR study of an α-keratin sourced from equine hoof has revealed a strong dependence of molecular conformation and molecular dynamics on the degree of hydration of the material. 13C cross-polarization, magic-angle spinning experiments were used in conjunction with two-dimensional 13C-1H WISE and 2H NMR to provide a detailed examination of these factors. In particular, dehydration results in a much more rigid and ordered structure, with a loss of α-helical components in the structure and breaking of cysteine disulfide linkages. These results have clear implications for our understanding of the material properties of equine hoof wall.
Co-reporter:Matthew D. Jones, Melinda J. Duer
Inorganica Chimica Acta 2003 Volume 354() pp:75-78
Publication Date(Web):30 October 2003
DOI:10.1016/S0020-1693(03)00173-7
An insight into the nature of the interaction between mesoporous solids and carbonyl clusters has been obtained from new solid-state NMR spectroscopic data. A series of simple clusters have been synthesised and deposited on the mesoporous material MCM-41. Results form 29Si{1H} solid-state NMR on both the pure and deposited species and 59Co NMR give rise to information about the nature of the cluster and its binding in the channels of the mesoporous material. Analysis of 29Si{1H} variable contact time experiments shows a significant increase in the rate of cross polarisation, particularly for the Q4 sites, once MCM-41 is deposited with a carbonyl cluster. 59Co NMR shows that the Co(CO)4 − cluster retains its original geometry when deposited in MCM-41.Metal carbonyl cluster anchored onto mesoporous silica are becoming class of xatalysts for industry. This article uses variable contact time 29Si CP/MAS to study these systems. The result from which shed new light into how these clusters are anchored to the mesoporous material.
Co-reporter:Matthew D. Jones Dr.;Sophie Hermans Dr.;Yaroslav Z. Khimyak Dr.;Brian F. G. Johnson ;John Meurig Thomas Sir
Angewandte Chemie 2002 Volume 114(Issue 24) pp:
Publication Date(Web):12 DEC 2002
DOI:10.1002/ange.200290028
Neue Erkenntnisse zur Bindung von Dimetallclustern und katalytisch aktiven Nanopartikeln an den mesoporösen Feststoff MCM-41 liefern Festkörper-NMR-Spektren (siehe Bild, rechts). Anhand solcher Untersuchungen wird ein Modell vorgeschlagen, das die Wechselwirkungen zwischen den Porenwänden und dem Cluster erklärt, und nachgewiesen, dass die Gegenionen eine wichtige Rolle bei der Verankerung spielen (siehe Bild, links).
Co-reporter:Matthew D. Jones Dr.;Sophie Hermans Dr.;Yaroslav Z. Khimyak Dr.;Brian F. G. Johnson ;John Meurig Thomas Sir
Angewandte Chemie International Edition 2002 Volume 41(Issue 24) pp:
Publication Date(Web):12 DEC 2002
DOI:10.1002/anie.200290029
New insight into the binding modes of bimetallic clusters and catalytically active nanoparticles to the mesoporous solid MCM-41 has been obtained from solid-state NMR spectroscopic data (see figure, right). From this study, a model has been proposed to explain the interactions between the pore walls and the cluster. It has been shown that the counterion plays an important role in the anchoring process (see figure, left).
Co-reporter:Yang Li, David G. Reid, Dominique Bazin, Michel Daudon, Melinda J. Duer
Comptes Rendus Chimie (November–December 2016) Volume 19(Issues 11–12) pp:
Publication Date(Web):November–December 2016
DOI:10.1016/j.crci.2015.07.001
Solid state NMR (ssNMR) can characterize mineral (31P) and organic (13C) components of human salivary stones (n = 8). All show apatitic 31P spectra. 13C ssNMR indicates more protein, of more consistent composition, than apatitic uroliths, with prominent signals from Tyr, Phe, and His. Citrate and lipids, identified by dipolar dephasing (DD), and polysaccharides are also observable in varying amounts. 13C{31P} rotational echo double resonance (13C{31P} REDOR) identifies carbon atoms in close (
Co-reporter:Melinda J. Duer, Tomislav Friščić, Rachel C. Murray, David G. Reid, Erica R. Wise
Biophysical Journal (22 April 2009) Volume 96(Issue 8) pp:
Publication Date(Web):22 April 2009
DOI:10.1016/j.bpj.2008.12.3954
We have studied the atomic level structure of mineralized articular cartilage with heteronuclear solid-state NMR, our aims being to identify the inorganic species present at the surfaces of the mineral crystals which may interact with the surrounding organic matrix and to determine which components of the organic matrix are most closely involved with the mineral crystals. One-dimensional 1H and 31P and two-dimensional 1H-31P heteronuclear correlation NMR experiments show that the mineral component is very similar to that in bone with regard to its surface structure. 13C{31P} rotational echo double resonance experiments identify the organic molecules at the mineral surface as glycosaminoglycans, which concurs with our recent finding in bone. There is also evidence of γ-carboxyglutamic acid residues interacting with the mineral. However, other matrix components appear more distant from the mineral compared with bone. This may be due to a larger hydration layer on the mineral crystal surfaces in calcified cartilage.
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