Pub Date : 2024-10-28DOI: 10.1016/j.jmro.2024.100171
Nele Reimets, Kerti Ausmees, Indrek Reile
Non-hydrogenative PHIP (nh-PHIP) is an NMR signal enhancement technique that offers several orders of magnitude gains in detection sensitivity. It is one of the few hyperpolarization methods that have been demonstrated to be applicable to chemical analysis of biological samples and potentially metabolomics. It is, however, a chemoselective method and needs to be tuned to particular analyte and metabolite classes at a time.
Herein, we present a systematic study where we apply four nh-PHIP modifications to urine samples from two different species – human and dog. Firstly, this allows to explore the whole analyte class scope and present what information is nh-PHIP capable of providing by varying the composition of the nh-PHIP catalyst system and the sample preparation protocol. Secondly, comparing hyperpolarized spectra from urines from different species demonstrates that this hyperpolarization technique is robust and tolerant of possibly considerable matrix differences: signals of the same metabolites appear at same chemical shifts from urines that differ from one-another much more than is likely in a realistic metabolomics study. Thereby we propose the idea that nh-PHIP is ready for application in metabolomics experiments.
{"title":"Current state of the art of analyte scope in urine metabolome analysis by non-hydrogenative PHIP","authors":"Nele Reimets, Kerti Ausmees, Indrek Reile","doi":"10.1016/j.jmro.2024.100171","DOIUrl":"10.1016/j.jmro.2024.100171","url":null,"abstract":"<div><div>Non-hydrogenative PHIP (nh-PHIP) is an NMR signal enhancement technique that offers several orders of magnitude gains in detection sensitivity. It is one of the few hyperpolarization methods that have been demonstrated to be applicable to chemical analysis of biological samples and potentially metabolomics. It is, however, a chemoselective method and needs to be tuned to particular analyte and metabolite classes at a time.</div><div>Herein, we present a systematic study where we apply four nh-PHIP modifications to urine samples from two different species – human and dog. Firstly, this allows to explore the whole analyte class scope and present what information is nh-PHIP capable of providing by varying the composition of the nh-PHIP catalyst system and the sample preparation protocol. Secondly, comparing hyperpolarized spectra from urines from different species demonstrates that this hyperpolarization technique is robust and tolerant of possibly considerable matrix differences: signals of the same metabolites appear at same chemical shifts from urines that differ from one-another much more than is likely in a realistic metabolomics study. Thereby we propose the idea that nh-PHIP is ready for application in metabolomics experiments.</div></div>","PeriodicalId":365,"journal":{"name":"Journal of Magnetic Resonance Open","volume":"21 ","pages":"Article 100171"},"PeriodicalIF":2.624,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142587184","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-10DOI: 10.1016/j.jmro.2024.100169
D. Panariti , B.J. Bayard , A. Barbon , Y.E. Kandrashkin , P.K. Poddutoori , A. van der Est , M. Di Valentin
Photoexcited triplet states of porphyrins are of great relevance in various applications due to their high yield, long lifetime, and strong electron spin polarization. This study delves into properties and spin dynamics of the triplet state of a series of hypervalent phosphorus(V) porphyrins. Transient Electron Paramagnetic Resonance (TrEPR) measurements, supported by quantum chemical calculations as well as by optical absorption/luminescence experiments, reveal that, unlike singlet states, the lowest triplet state does not exhibit charge-transfer (CT) character upon photoexcitation. However, the presence of excited CT singlet states alters the intersystem crossing in phosphorus(V) porphyrins, leading to a sign change in the initial multiplet polarization of the photoexcited triplet state. TrEPR results further demonstrate that significant net polarization develops in the triplet states of the phosphorus(V) porphyrins due to the dynamic Jahn-Teller effect. Yet, this effect remains largely unaffected by differences in their molecular structures.
{"title":"Electron spin polarization in the triplet state of methoxy-substituted phosphorus(V) tetraphenyl porphyrins","authors":"D. Panariti , B.J. Bayard , A. Barbon , Y.E. Kandrashkin , P.K. Poddutoori , A. van der Est , M. Di Valentin","doi":"10.1016/j.jmro.2024.100169","DOIUrl":"10.1016/j.jmro.2024.100169","url":null,"abstract":"<div><div>Photoexcited triplet states of porphyrins are of great relevance in various applications due to their high yield, long lifetime, and strong electron spin polarization. This study delves into properties and spin dynamics of the triplet state of a series of hypervalent phosphorus(V) porphyrins. Transient Electron Paramagnetic Resonance (TrEPR) measurements, supported by quantum chemical calculations as well as by optical absorption/luminescence experiments, reveal that, unlike singlet states, the lowest triplet state does not exhibit charge-transfer (CT) character upon photoexcitation. However, the presence of excited CT singlet states alters the intersystem crossing in phosphorus(V) porphyrins, leading to a sign change in the initial multiplet polarization of the photoexcited triplet state. TrEPR results further demonstrate that significant net polarization develops in the triplet states of the phosphorus(V) porphyrins due to the dynamic Jahn-Teller effect. Yet, this effect remains largely unaffected by differences in their molecular structures.</div></div>","PeriodicalId":365,"journal":{"name":"Journal of Magnetic Resonance Open","volume":"21 ","pages":"Article 100169"},"PeriodicalIF":2.624,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142704450","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-09DOI: 10.1016/j.jmro.2024.100167
Zhuoran Wang , Thomas C. Robinson , Domenico Gioffrè , Rochlitz Lukas , David Gajan , Aaron J. Rossini , Christophe Copéret , Anne Lesage
Surface organometallic chemistry has developed as an effective strategy for the rational design and synthesis of well-defined, single-site Pt-based heterogeneous catalysts. Given its high sensitivity to changes in electronic structure, 195Pt solid-state NMR spectroscopy offers a unique approach to investigate the chemical structure and local environment of Pt surface sites, providing invaluable insights for establishing structure-activity relationships. However, this approach is typically hindered by severe sensitivity issues, due to the low loading of Pt sites and the often-encountered large 195Pt chemical shift anisotropies. To overcome this limitation, 195Pt NMR signature of surface metal centers can be indirectly detected through protons. Indirect detection on 13C spins, has also been demonstrated to be feasible by combining isotopic labeling with dynamic nuclear polarization (DNP). Here, we extend this methodology to a supported Pt complex at natural abundance. The material was prepared by grafting (COD)PtMeOSi(OtBu)3 (COD = 1,5-cyclooctadiene, Me = methyl and tBu = tert‑butyl) onto partially dehydroxylated silica. DNP enhanced two-dimensional through-bond 13C{195Pt} heteronuclear correlation experiments were successfully implemented at fast magic angle spinning. They enabled the detection of the 0.37 % NMR-responsive surface species, thereby showcasing the remarkable sensitivity of this approach and its broad applicability. Key bonding information was obtained by measuring the correlated 13C and 195Pt isotopic chemical shifts as well as 1J(13C-195Pt) coupling constants, confirming directly the coordination structure of the surface Pt sites.
{"title":"Natural abundance 195Pt-13C correlation NMR spectroscopy on surfaces enabled by fast MAS dynamic nuclear polarization","authors":"Zhuoran Wang , Thomas C. Robinson , Domenico Gioffrè , Rochlitz Lukas , David Gajan , Aaron J. Rossini , Christophe Copéret , Anne Lesage","doi":"10.1016/j.jmro.2024.100167","DOIUrl":"10.1016/j.jmro.2024.100167","url":null,"abstract":"<div><div>Surface organometallic chemistry has developed as an effective strategy for the rational design and synthesis of well-defined, single-site Pt-based heterogeneous catalysts. Given its high sensitivity to changes in electronic structure, <sup>195</sup>Pt solid-state NMR spectroscopy offers a unique approach to investigate the chemical structure and local environment of Pt surface sites, providing invaluable insights for establishing structure-activity relationships. However, this approach is typically hindered by severe sensitivity issues, due to the low loading of Pt sites and the often-encountered large <sup>195</sup>Pt chemical shift anisotropies. To overcome this limitation, <sup>195</sup>Pt NMR signature of surface metal centers can be indirectly detected through protons. Indirect detection on <sup>13</sup>C spins, has also been demonstrated to be feasible by combining isotopic labeling with dynamic nuclear polarization (DNP). Here, we extend this methodology to a supported Pt complex at natural abundance. The material was prepared by grafting <strong>(COD)PtMeOSi(O<em>t</em>Bu)<sub>3</sub></strong> (COD = 1,5-cyclooctadiene, Me = methyl and <em>t</em>Bu = <em>tert</em>‑butyl) onto partially dehydroxylated silica. DNP enhanced two-dimensional through-bond <sup>13</sup>C{<sup>195</sup>Pt} heteronuclear correlation experiments were successfully implemented at fast magic angle spinning. They enabled the detection of the 0.37 % NMR-responsive surface species, thereby showcasing the remarkable sensitivity of this approach and its broad applicability. Key bonding information was obtained by measuring the correlated <sup>13</sup>C and <sup>195</sup>Pt isotopic chemical shifts as well as <sup>1</sup><em>J</em>(<sup>13</sup>C-<sup>195</sup>Pt) coupling constants, confirming directly the coordination structure of the surface Pt sites.</div></div>","PeriodicalId":365,"journal":{"name":"Journal of Magnetic Resonance Open","volume":"21 ","pages":"Article 100167"},"PeriodicalIF":2.624,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142434013","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-05DOI: 10.1016/j.jmro.2024.100168
Patrick Kurle-Tucholski , Luca Gerhards , Yonghong Ding , Yunmi Kim , Irina S. Anisimova , A. Alia , Ilia A. Solov'yov , Jörg Matysik
The solid-state photo-CIDNP (photo-chemically induced dynamic nuclear polarization) effect allows for nuclear hyperpolarization, i.e., non-Boltzmann nuclear spin population. The effect relies on the light-induced formation of a spin-correlated radical pair (SCRP) and has been observed in various photosynthetic reaction center (RC) proteins and flavin-containing light, oxygen, voltage (LOV) proteins. Both systems exhibit strongly enhanced NMR signals originating from the electron transfer partners. Here, we present experimental data on the magnetic field dependence of the 15N solid-state photo-CIDNP effect in both phototropin LOV1 C57S from Chlamydomonas reinhardtii and the bacterial photosynthetic RC from Rhodobacter sphaeroides. Using a pneumatic field-cycling system, samples containing a frozen solution of the proteins are explored between 0.25 T and 9.4 T. Both systems yield hyperpolarized 15N NMR signals across the entire magnetic field range originating from the electron transfer moieties. Also, in both systems, hyperpolarized signals from unexpected positions are detected between 1.0 T and 2.0 T: position N-1 of the flavin in the LOV1 protein and the τ-N of the axial magnesium-coordinating histidine of the donor. A first attempt to explain the occurrence of these unexpected signals based on quantum chemical calculations is presented.
固态光-CIDNP（光化学诱导动态核极化）效应允许核超极化，即非玻尔兹曼核自旋群。这种效应依赖于光诱导形成的自旋相关自由基对（SCRP），并已在各种光合反应中心（RC）蛋白质和含黄素的光、氧、电压（LOV）蛋白质中观察到。这两个系统都显示出源自电子转移伴侣的强烈增强 NMR 信号。在这里，我们展示了有关 15N 固态光-CIDNP 效应在莱茵衣藻的趋光蛋白 LOV1 C57S 和孢氏红杆菌的细菌光合 RC 中的磁场依赖性的实验数据。利用气动磁场循环系统，在 0.25 T 和 9.4 T 之间对含有冷冻蛋白质溶液的样品进行了探究。在整个磁场范围内，两个系统都产生了源于电子传递分子的超极化 15N NMR 信号。此外，在这两个系统中，在 1.0 T 和 2.0 T 之间都检测到了来自意外位置的超极化信号：LOV1 蛋白中黄素的 N-1 位置和供体的轴向镁配位组氨酸的 τ-N 位置。本文首次尝试根据量子化学计算来解释这些意外信号的出现。
{"title":"Nuclear hyperpolarization in electron-transfer proteins: Revealing unexpected light-induced 15N signals with field-cycling magic-angle spinning NMR","authors":"Patrick Kurle-Tucholski , Luca Gerhards , Yonghong Ding , Yunmi Kim , Irina S. Anisimova , A. Alia , Ilia A. Solov'yov , Jörg Matysik","doi":"10.1016/j.jmro.2024.100168","DOIUrl":"10.1016/j.jmro.2024.100168","url":null,"abstract":"<div><div>The solid-state photo-CIDNP (photo-chemically induced dynamic nuclear polarization) effect allows for nuclear hyperpolarization, i.e., non-Boltzmann nuclear spin population. The effect relies on the light-induced formation of a spin-correlated radical pair (SCRP) and has been observed in various photosynthetic reaction center (RC) proteins and flavin-containing light, oxygen, voltage (LOV) proteins. Both systems exhibit strongly enhanced NMR signals originating from the electron transfer partners. Here, we present experimental data on the magnetic field dependence of the <sup>15</sup>N solid-state photo-CIDNP effect in both phototropin LOV1 C57S from <em>Chlamydomonas reinhardtii</em> and the bacterial photosynthetic RC from <em>Rhodobacter sphaeroides.</em> Using a pneumatic field-cycling system, samples containing a frozen solution of the proteins are explored between 0.25 T and 9.4 T. Both systems yield hyperpolarized <sup>15</sup>N NMR signals across the entire magnetic field range originating from the electron transfer moieties. Also, in both systems, hyperpolarized signals from unexpected positions are detected between 1.0 T and 2.0 T: position N-1 of the flavin in the LOV1 protein and the τ-N of the axial magnesium-coordinating histidine of the donor. A first attempt to explain the occurrence of these unexpected signals based on quantum chemical calculations is presented.</div></div>","PeriodicalId":365,"journal":{"name":"Journal of Magnetic Resonance Open","volume":"21 ","pages":"Article 100168"},"PeriodicalIF":2.624,"publicationDate":"2024-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142427347","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-23DOI: 10.1016/j.jmro.2024.100166
Graham Norquay , Madhwesha R Rao , Jim M Wild
Background
The feasibility of imaging hyperpolarized 129Xe dissolved in brain tissue following inhalation of xenon gas in the lungs has recently been demonstrated in humans. The image contrast in 129Xe brain MRI represents a combination of factors, including regional perfusion, polarization decay and gas transfer rate across the blood-brain barrier.
Purpose
To investigate the repeatability of hyperpolarized 129Xe brain MRI in healthy normal individuals and to identify the dominant mechanisms of image contrast by assessing voxel-wise correlation between HP 129Xe brain MRI and models of 129Xe brain uptake derived from 1H arterial spin labeling (ASL) perfusion mapping.
Materials and Methods
To assess repeatability, 3 sets of hyperpolarized 129Xe brain images were acquired from 5 healthy volunteers. Quantitative maps of the human brain, including cerebral blood flow, volume and predicted xenon uptake, were derived from 1H arterial spin labeling and T2-weighted MRI. These maps were then spatially cross-correlated with hyperpolarized 129Xe brain MRI.
Results
Signal to noise ratios of 8.7–17.7 were observed across volunteers for a voxel size of 8 × 8 × 50 mm3 with intra-subject repeatability of between 6 and 29 %. Hyperpolarized 129Xe brain images showed voxel-wise correlations with cerebral blood flow (R = 0.32 to 0.62), volume (R = 0.33 to 0.63) and predicted xenon uptake (R = 0.34 to 0.63), but did not correlate with arterial transit time (R = 0.05 to 0.26).
Conclusion
Voxel-wise cross correlation between 129Xe and 1H ASL suggests that the regional quantity of dissolved xenon delivered by cerebral blood flow is the dominant mechanism of image contrast in HP 129Xe brain MRI, assuming normal blood-brain barrier function. Combining 1H and 129Xe brain MRI provides new opportunities to quantitatively investigate brain pathophysiology and function.
{"title":"Measurement and modeling of xenon gas transfer in the human brain with 1H and hyperpolarized 129Xe MRI","authors":"Graham Norquay , Madhwesha R Rao , Jim M Wild","doi":"10.1016/j.jmro.2024.100166","DOIUrl":"10.1016/j.jmro.2024.100166","url":null,"abstract":"<div><h3>Background</h3><div>The feasibility of imaging hyperpolarized <sup>129</sup>Xe dissolved in brain tissue following inhalation of xenon gas in the lungs has recently been demonstrated in humans. The image contrast in <sup>129</sup>Xe brain MRI represents a combination of factors, including regional perfusion, polarization decay and gas transfer rate across the blood-brain barrier.</div></div><div><h3>Purpose</h3><div>To investigate the repeatability of hyperpolarized <sup>129</sup>Xe brain MRI in healthy normal individuals and to identify the dominant mechanisms of image contrast by assessing voxel-wise correlation between HP <sup>129</sup>Xe brain MRI and models of <sup>129</sup>Xe brain uptake derived from <sup>1</sup>H arterial spin labeling (ASL) perfusion mapping.</div></div><div><h3>Materials and Methods</h3><div>To assess repeatability, 3 sets of hyperpolarized <sup>129</sup>Xe brain images were acquired from 5 healthy volunteers. Quantitative maps of the human brain, including cerebral blood flow, volume and predicted xenon uptake, were derived from <sup>1</sup>H arterial spin labeling and <em>T</em><sub>2</sub>-weighted MRI. These maps were then spatially cross-correlated with hyperpolarized <sup>129</sup>Xe brain MRI.</div></div><div><h3>Results</h3><div>Signal to noise ratios of 8.7–17.7 were observed across volunteers for a voxel size of 8 × 8 × 50 mm<sup>3</sup> with intra-subject repeatability of between 6 and 29 %. Hyperpolarized <sup>129</sup>Xe brain images showed voxel-wise correlations with cerebral blood flow (<em>R</em> = 0.32 to 0.62), volume (<em>R</em> = 0.33 to 0.63) and predicted xenon uptake (<em>R</em> = 0.34 to 0.63), but did not correlate with arterial transit time (<em>R</em> = 0.05 to 0.26).</div></div><div><h3>Conclusion</h3><div>Voxel-wise cross correlation between <sup>129</sup>Xe and <sup>1</sup>H ASL suggests that the regional quantity of dissolved xenon delivered by cerebral blood flow is the dominant mechanism of image contrast in HP <sup>129</sup>Xe brain MRI, assuming normal blood-brain barrier function. Combining <sup>1</sup>H and <sup>129</sup>Xe brain MRI provides new opportunities to quantitatively investigate brain pathophysiology and function.</div></div>","PeriodicalId":365,"journal":{"name":"Journal of Magnetic Resonance Open","volume":"21 ","pages":"Article 100166"},"PeriodicalIF":2.624,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142327332","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-23DOI: 10.1016/j.jmro.2024.100162
Stuart J. Elliott , Quentin Stern, Sami Jannin
1H polarization quantification is important for dissolution-dynamic nuclear polarization (dDNP) but can be cumbersome due to the requirement of acquiring thermal equilibrium signals and measurements that are complicated by large background signals. 1H nuclear magnetic resonance (NMR) spectra can also be deleteriously influenced by line distortions linked with radiation damping from 1H DNP and cannot be used for accurate calculation of 1H polarization. Determining 1H polarization via immediate 13C lineshape analysis of a simple molecule removes such complications. We present 13C-sodium formate as a straightforward system for indirect 1H polarimetry. The 13C NMR spectra acquired under dDNP conditions have distinct features that are readily reproduced with 13C lineshape simulations. 1H polarizations built-up during 1H DNP were indirectly inferred by fitting simulations to 13C lineshapes. We provide the MATLAB scripts used for 13C lineshape analysis in order that the method can be readily implemented in other laboratories.
{"title":"13C-Formate as an indirect low-temperature 1H lineshape polarimeter","authors":"Stuart J. Elliott , Quentin Stern, Sami Jannin","doi":"10.1016/j.jmro.2024.100162","DOIUrl":"10.1016/j.jmro.2024.100162","url":null,"abstract":"<div><div><sup>1</sup>H polarization quantification is important for dissolution-dynamic nuclear polarization (<em>d</em>DNP) but can be cumbersome due to the requirement of acquiring thermal equilibrium signals and measurements that are complicated by large background signals. <sup>1</sup>H nuclear magnetic resonance (NMR) spectra can also be deleteriously influenced by line distortions linked with radiation damping from <sup>1</sup>H DNP and cannot be used for accurate calculation of <sup>1</sup>H polarization. Determining <sup>1</sup>H polarization via immediate <sup>13</sup>C lineshape analysis of a simple molecule removes such complications. We present <sup>13</sup>C-sodium formate as a straightforward system for indirect <sup>1</sup>H polarimetry. The <sup>13</sup>C NMR spectra acquired under <em>d</em>DNP conditions have distinct features that are readily reproduced with <sup>13</sup>C lineshape simulations. <sup>1</sup>H polarizations built-up during <sup>1</sup>H DNP were indirectly inferred by fitting simulations to <sup>13</sup>C lineshapes. We provide the <em>MATLAB</em> scripts used for <sup>13</sup>C lineshape analysis in order that the method can be readily implemented in other laboratories.</div></div>","PeriodicalId":365,"journal":{"name":"Journal of Magnetic Resonance Open","volume":"21 ","pages":"Article 100162"},"PeriodicalIF":2.624,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142427292","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-18DOI: 10.1016/j.jmro.2024.100161
Thomas Biedenbänder , Aryana Rodgers , Mirjam Schröder , Liliya Vugmeyster , Björn Corzilius
Molecular dynamics of functional groups contain valuable information about structural properties and functional activities in biomolecules. NMR spectroscopy is a sensitive tool for the investigation of molecular dynamics over a wide range of timescales and thus may deepen the understanding of the biomolecules of interest. Here, we present an approach to use DNP-enhanced 2H NMR to study dynamics of selectively deuterated methyl groups in insoluble proteins such as amyloid beta (Aβ) fibrils. We adopted and optimized the matrix-free DNP approach by varying the amount of added polarizing agent as well as the rehydration level of model proteins. We show that the DNP enhancement obtained in 1H–2H cross-polarization (CP) MAS spectra may increase the sensitivity for selectively deuterated Aβ fibril samples by more than one order of magnitude, accelerating the collection of spin-lattice relaxation data in the DNP-accessible temperature range between 100 and 150 K by up to 400-fold. However, below the coalescence temperature, which describes the transition from the fast to the slow exchange regime, the experimentally obtained relaxation time constants suffer from a paramagnetic relaxation enhancement effect due to the presence of the polarizing agent. This seems to be a general effect for biomolecules as it is also confirmed for two other protein model systems. Our demonstration opens the possibility to extend the scope of 2H NMR for dynamics measurements to effective concentrations and/or temperatures below what is currently accessible; however, the observed interplay between paramagnetic relaxation and molecular dynamics also emphasizes the necessity for a better understanding of relaxation effects in DNP-enhanced NMR.
{"title":"Investigation of biomolecular dynamics by sensitivity-enhanced 1H–2H CPMAS NMR using matrix-free dynamic nuclear polarization","authors":"Thomas Biedenbänder , Aryana Rodgers , Mirjam Schröder , Liliya Vugmeyster , Björn Corzilius","doi":"10.1016/j.jmro.2024.100161","DOIUrl":"10.1016/j.jmro.2024.100161","url":null,"abstract":"<div><div>Molecular dynamics of functional groups contain valuable information about structural properties and functional activities in biomolecules. NMR spectroscopy is a sensitive tool for the investigation of molecular dynamics over a wide range of timescales and thus may deepen the understanding of the biomolecules of interest. Here, we present an approach to use DNP-enhanced <sup>2</sup>H NMR to study dynamics of selectively deuterated methyl groups in insoluble proteins such as amyloid beta (Aβ) fibrils. We adopted and optimized the matrix-free DNP approach by varying the amount of added polarizing agent as well as the rehydration level of model proteins. We show that the DNP enhancement obtained in <sup>1</sup>H–<sup>2</sup>H cross-polarization (CP) MAS spectra may increase the sensitivity for selectively deuterated Aβ fibril samples by more than one order of magnitude, accelerating the collection of spin-lattice relaxation data in the DNP-accessible temperature range between 100 and 150 K by up to 400-fold. However, below the coalescence temperature, which describes the transition from the fast to the slow exchange regime, the experimentally obtained relaxation time constants suffer from a paramagnetic relaxation enhancement effect due to the presence of the polarizing agent. This seems to be a general effect for biomolecules as it is also confirmed for two other protein model systems. Our demonstration opens the possibility to extend the scope of <sup>2</sup>H NMR for dynamics measurements to effective concentrations and/or temperatures below what is currently accessible; however, the observed interplay between paramagnetic relaxation and molecular dynamics also emphasizes the necessity for a better understanding of relaxation effects in DNP-enhanced NMR.</div></div>","PeriodicalId":365,"journal":{"name":"Journal of Magnetic Resonance Open","volume":"21 ","pages":"Article 100161"},"PeriodicalIF":2.624,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142320067","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-14DOI: 10.1016/j.jmro.2024.100163
Mark V. Höfler , Jonas Lins , David Seelinger , Lukas Pachernegg , Timmy Schäfer , Stefan Spirk , Markus Biesalski , Torsten Gutmann
This concept summarizes recent advances in development and application of DNP enhanced multinuclear solid-state NMR to study the molecular structure and surface functionalization of cellulose and paper-based materials. Moreover, a novel application is presented where DNP enhanced 13C and 15N solid-state NMR is used to identify structure moieties formed by cross-linking of hydroxypropyl cellulose. Given these two aspects of this concept-type of article, we thus combine both, a review on recent findings already published and unpublished recent data that complement the existing knowledge in the field of characterization of functional lignocellulosic materials by DNP enhanced solid-state NMR.
{"title":"DNP enhanced solid-state NMR – A powerful tool to address the surface functionalization of cellulose/paper derived materials","authors":"Mark V. Höfler , Jonas Lins , David Seelinger , Lukas Pachernegg , Timmy Schäfer , Stefan Spirk , Markus Biesalski , Torsten Gutmann","doi":"10.1016/j.jmro.2024.100163","DOIUrl":"10.1016/j.jmro.2024.100163","url":null,"abstract":"<div><div>This concept summarizes recent advances in development and application of DNP enhanced multinuclear solid-state NMR to study the molecular structure and surface functionalization of cellulose and paper-based materials. Moreover, a novel application is presented where DNP enhanced <sup>13</sup>C and <sup>15</sup>N solid-state NMR is used to identify structure moieties formed by cross-linking of hydroxypropyl cellulose. Given these two aspects of this concept-type of article, we thus combine both, a review on recent findings already published and unpublished recent data that complement the existing knowledge in the field of characterization of functional lignocellulosic materials by DNP enhanced solid-state NMR.</div></div>","PeriodicalId":365,"journal":{"name":"Journal of Magnetic Resonance Open","volume":"21 ","pages":"Article 100163"},"PeriodicalIF":2.624,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142320068","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-11DOI: 10.1016/j.jmro.2024.100165
Ivan de Kouchkovsky , Hao Nguyen , Hsin-Yu Chen , Xiaoxi Liu , Hecong Qin , Bradley A. Stohr , Romelyn Delos Santos , Michael A. Ohliger , Zhen Jane Wang , Robert A. Bok , Jeremy W. Gordon , Peder E.Z. Larson , Mary Frost , Kimberly Okamoto , Daniel Gebrezgiabhier , Matthew Cooperberg , Daniel B. Vigneron , John Kurhanewicz , Rahul Aggarwal
<div><h3>Background</h3><p>Although multiparametric (mp) <sup>1</sup>H magnetic resonance imaging (MRI) is increasingly used to detect and localize prostate cancer (PC), its correlation with tumor grade is limited. Hyperpolarized (HP) carbon-13 (<sup>13</sup>C) MR is an emerging imaging technique, which can be used to interrogate key biologic processes through in vivo detection of various HP probes. A distinct attribute of HP <sup>13</sup>C MRI is the ability to detect multiple HP probes within a single acquisition. Here we report on the first simultaneous dual HP [1-<sup>13</sup>C]pyruvate and [<sup>13</sup>C]urea MRI with correlations to histopathologic findings in a patient with localized PC scheduled for radical prostatectomy.</p></div><div><h3>Material and methods</h3><p>Paired HP <sup>13</sup>C and standard mp <sup>1</sup>H MRI were performed in a patient with biopsy-proven Gleason score 4 + 3 = 7 adenocarcinoma of the prostate scheduled for radical prostatectomy through a first-in-human pilot study of dual-agent HP MRI (NCT02526368). HP <sup>13</sup>C MRI was performed using a clinical 3T scanner with <sup>13</sup>C transmit-and-receive capabilities. Dynamic series of HP <sup>13</sup>C pyruvate, lactate and urea imaging were acquired following intravenous (IV) injection of co-hyperpolarized [<sup>13</sup>C]urea (25 mM) and [1–<sup>13</sup>C]pyruvate (125 mM). The [1-<sup>13</sup>C]pyruvate-to-[1-<sup>13</sup>C]lactate conversion rate (k<sub>PL</sub>) was calculated using an inputless two-site exchange model; AUC<sub>urea</sub> was the [<sup>13</sup>C]urea signal summed over time. Following radical prostatectomy, whole-mount prostate histopathological slides were prepared and reviewed by an experienced genitourinary pathologist.</p></div><div><h3>Results</h3><p>Following informed consent, the patient underwent paired mp <sup>1</sup>H MRI and dual-agent HP MRI. mp <sup>1</sup>H MRI revealed a 1.2 cm lesion in the left apical posterior zone. Dual-agent HP MRI identified a focus of increased [1-<sup>13</sup>C]pyruvate-to-[1-<sup>13</sup>C]lactate conversion rate (k<sub>PL</sub>) extending from the left apical posterior peripheral zone to the right gland. A corresponding area of abnormal tissue perfusion (AUC<sub>urea</sub>) was seen in the left gland. Metabolism-perfusion mismatch (with several foci of increased <em>k<sub>PL</sub></em>/AUC<sub>urea</sub>) was observed throughout the tumor. Tumor extension to the right midgland was confirmed at the time of radical prostatectomy and staining for lactate dehydrogenase-A was increased throughout the tumor relative to surrounding benign prostatic tissue.</p></div><div><h3>Conclusion</h3><p>This first-in-human radiopathologic study demonstrates the feasibility of dual-agent HP MRI in PC patients. Simultaneous assessment of tumor metabolism and perfusion was able to detect occult disease as well as to show a significant mismatch between intra-tumoral metabolism and tissue perfusion in high-grade PC.
背景虽然多参数（mp）1H 磁共振成像（MRI）越来越多地用于检测和定位前列腺癌（PC），但其与肿瘤分级的相关性有限。超极化（HP）碳-13（13C）磁共振成像是一种新兴的成像技术，可通过在体内检测各种 HP 探针来探查关键的生物过程。HP 13C MRI 的一个显著特点是能在一次采集中检测多个 HP 探针。在此，我们报告了首次同时进行的双 HP [1-13C] 丙酮酸和 [13C] 尿素 MRI 与组织病理学检查结果的相关性，该患者患有局部 PC，计划进行根治性前列腺切除术。材料和方法通过首次在人体中进行的双试剂 HP MRI 试验研究（NCT02526368），对一名经活检证实 Gleason 评分为 4 + 3 = 7 的前列腺腺癌患者进行了成对 HP 13C 和标准 mp 1H MRI。HP 13C MRI 是使用具有 13C 发射和接收功能的临床 3T 扫描仪进行的。在静脉注射共超极化[13C]尿素（25 mM）和[1-13C]丙酮酸（125 mM）后，采集了一系列动态的 HP 13C 丙酮酸、乳酸和尿素成像。[1-13C]丙酮酸到[1-13C]乳酸的转化率（kPL）是通过无输入的双位点交换模型计算得出的；AUCurea是[13C]尿素信号在一段时间内的总和。根治性前列腺切除术后，由经验丰富的泌尿生殖系统病理学家制备并审查整张前列腺组织病理切片。结果在知情同意后，患者接受了成对的 mp 1H MRI 和双试剂 HP MRI 检查。双剂 HP MRI 发现一个[1-13C]丙酮酸-[1-13C]乳酸转化率（kPL）升高的病灶，从左侧心尖后外周区延伸至右侧腺体。左侧腺体出现了相应的组织灌注异常区域（AUCurea）。整个肿瘤都出现了代谢-灌注不匹配现象（有几个 kPL/AUCurea 增高的病灶）。根治性前列腺切除术时证实肿瘤扩展到了右侧腺体中部，与周围良性前列腺组织相比，整个肿瘤的乳酸脱氢酶-A染色增加。同时评估肿瘤的代谢和灌注能够检测出隐匿性疾病，并显示高级别 PC 中肿瘤内代谢和组织灌注之间存在明显的不匹配。有必要对这些发现进行前瞻性验证。
{"title":"Dual hyperpolarized [1-13C]pyruvate and [13C]urea magnetic resonance imaging of prostate cancer","authors":"Ivan de Kouchkovsky , Hao Nguyen , Hsin-Yu Chen , Xiaoxi Liu , Hecong Qin , Bradley A. Stohr , Romelyn Delos Santos , Michael A. Ohliger , Zhen Jane Wang , Robert A. Bok , Jeremy W. Gordon , Peder E.Z. Larson , Mary Frost , Kimberly Okamoto , Daniel Gebrezgiabhier , Matthew Cooperberg , Daniel B. Vigneron , John Kurhanewicz , Rahul Aggarwal","doi":"10.1016/j.jmro.2024.100165","DOIUrl":"10.1016/j.jmro.2024.100165","url":null,"abstract":"<div><h3>Background</h3><p>Although multiparametric (mp) <sup>1</sup>H magnetic resonance imaging (MRI) is increasingly used to detect and localize prostate cancer (PC), its correlation with tumor grade is limited. Hyperpolarized (HP) carbon-13 (<sup>13</sup>C) MR is an emerging imaging technique, which can be used to interrogate key biologic processes through in vivo detection of various HP probes. A distinct attribute of HP <sup>13</sup>C MRI is the ability to detect multiple HP probes within a single acquisition. Here we report on the first simultaneous dual HP [1-<sup>13</sup>C]pyruvate and [<sup>13</sup>C]urea MRI with correlations to histopathologic findings in a patient with localized PC scheduled for radical prostatectomy.</p></div><div><h3>Material and methods</h3><p>Paired HP <sup>13</sup>C and standard mp <sup>1</sup>H MRI were performed in a patient with biopsy-proven Gleason score 4 + 3 = 7 adenocarcinoma of the prostate scheduled for radical prostatectomy through a first-in-human pilot study of dual-agent HP MRI (NCT02526368). HP <sup>13</sup>C MRI was performed using a clinical 3T scanner with <sup>13</sup>C transmit-and-receive capabilities. Dynamic series of HP <sup>13</sup>C pyruvate, lactate and urea imaging were acquired following intravenous (IV) injection of co-hyperpolarized [<sup>13</sup>C]urea (25 mM) and [1–<sup>13</sup>C]pyruvate (125 mM). The [1-<sup>13</sup>C]pyruvate-to-[1-<sup>13</sup>C]lactate conversion rate (k<sub>PL</sub>) was calculated using an inputless two-site exchange model; AUC<sub>urea</sub> was the [<sup>13</sup>C]urea signal summed over time. Following radical prostatectomy, whole-mount prostate histopathological slides were prepared and reviewed by an experienced genitourinary pathologist.</p></div><div><h3>Results</h3><p>Following informed consent, the patient underwent paired mp <sup>1</sup>H MRI and dual-agent HP MRI. mp <sup>1</sup>H MRI revealed a 1.2 cm lesion in the left apical posterior zone. Dual-agent HP MRI identified a focus of increased [1-<sup>13</sup>C]pyruvate-to-[1-<sup>13</sup>C]lactate conversion rate (k<sub>PL</sub>) extending from the left apical posterior peripheral zone to the right gland. A corresponding area of abnormal tissue perfusion (AUC<sub>urea</sub>) was seen in the left gland. Metabolism-perfusion mismatch (with several foci of increased <em>k<sub>PL</sub></em>/AUC<sub>urea</sub>) was observed throughout the tumor. Tumor extension to the right midgland was confirmed at the time of radical prostatectomy and staining for lactate dehydrogenase-A was increased throughout the tumor relative to surrounding benign prostatic tissue.</p></div><div><h3>Conclusion</h3><p>This first-in-human radiopathologic study demonstrates the feasibility of dual-agent HP MRI in PC patients. Simultaneous assessment of tumor metabolism and perfusion was able to detect occult disease as well as to show a significant mismatch between intra-tumoral metabolism and tissue perfusion in high-grade PC. ","PeriodicalId":365,"journal":{"name":"Journal of Magnetic Resonance Open","volume":"21 ","pages":"Article 100165"},"PeriodicalIF":2.624,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666441024000207/pdfft?md5=7b66657cb74e70c1242c4491d6fa3a40&pid=1-s2.0-S2666441024000207-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142232386","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-02DOI: 10.1016/j.jmro.2024.100160
Alex van der Ham
Liquid-state Overhauser Dynamic Nuclear Polarization (ODNP) is an emerging technique, aimed at shortening NMR experiment times. It achieves this by increasing the otherwise poor nuclear polarization at room temperature, by polarization transfer from excited electron spins. The present work explores two ideas, aimed at achieving the optimal signal-to-noise per time unit for a given system, and quantitation of spectra showing a large disparity in ODNP enhancements at high magnetic fields (≥ 9.4 T). Both of these ideas are predicated on, perhaps counterintuitively, not allowing full dynamic nuclear polarization to build up, either by rapid rf pulsing, or gating of the microwave irradiation.
{"title":"Discontinuous hyperpolarization schemes in liquid-state overhauser dynamic nuclear polarization experiments","authors":"Alex van der Ham","doi":"10.1016/j.jmro.2024.100160","DOIUrl":"10.1016/j.jmro.2024.100160","url":null,"abstract":"<div><p>Liquid-state Overhauser Dynamic Nuclear Polarization (ODNP) is an emerging technique, aimed at shortening NMR experiment times. It achieves this by increasing the otherwise poor nuclear polarization at room temperature, by polarization transfer from excited electron spins. The present work explores two ideas, aimed at achieving the optimal signal-to-noise per time unit for a given system, and quantitation of spectra showing a large disparity in ODNP enhancements at high magnetic fields (≥ 9.4 T). Both of these ideas are predicated on, perhaps counterintuitively, not allowing full dynamic nuclear polarization to build up, either by rapid rf pulsing, or gating of the microwave irradiation.</p></div>","PeriodicalId":365,"journal":{"name":"Journal of Magnetic Resonance Open","volume":"21 ","pages":"Article 100160"},"PeriodicalIF":2.624,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666441024000153/pdfft?md5=1b851004339d56ccb0489d8db665fe26&pid=1-s2.0-S2666441024000153-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142167439","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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