Clinical-Scale Production and MRI of Hyperpolarized Propane: Potential 129Xe Alternative?

Oleg G. Salnikov2,3, Kirill V. Kovtunov2,3, Igor V. Koptyug2,3, Panayiotis Nikolaou1, Eduard Y. Chekmenev1 eduard_chekmenev@hotmail.com

1Wayne State University & Karmanos Cancer Center (KCC), Detroit, MI, United States

2International Tomography Center, 3A Institutskaya st., Novosibirsk 630090, Russia 3Novosibirsk State University, 2 Pirogova st., Novosibirsk 630090, Russia

BACKGROUND: Hyperpolarization techniques enhance nuclear magnetic resonance signals by orders of magnitude. Hyperpolarized (HP) 129Xe is currently the most promising agent for pulmonary imaging, because (i) it can be hyperpolarized to the order unity on a clinical scale [1], (ii) it is inert, and (iii) it has >7,000 chemical shift dispersion useful for sensing the environment. However, HP 129Xe technology faces several challenges for widespread clinical use: (i) moderate natural isotopic abundance of 129Xe (~26%), (ii) the need for high-cost hyperpolarization equipment, (iii) the requirement for a customized multinuclear capability of MRI scanner.

METHODS: HP propane has been shown a good candidate for pulmonary imaging and other non-biomedical applications [2]. Indeed, propane is a non-toxic gas, it can be readily hyperpolarized via pairwise hydrogenation of propylene with parahydrogen (Figure 1a), and it can be imaged using conventional proton hardware universally available on clinical MRI scanners. It has been demonstrated that the lifetime of hyperpolarized propane gas can be enhanced by a factor of more than three via the use of long-lived spin states at low magnetic fields—allowing in principle for its biomedical use as an inhalable contrast agent with T1 of 3-5 seconds at 1 atm [2,7]. RESULTS: Here, we present our most recent work on preparation of hyperpolarized propane on a clinical scale (~0.5 L of HP propane in 2.0 seconds) with nuclear spin polarization approaching 1% (greater polarization yields are potentially possible), which we confirm through NMR spectroscopy and more importantly MRI imaging (Figure 1c). Indeed, we find that the production of the clinically relevant scale can be as efficient as the production on a significantly smaller scale reported in earlier studies. We note that high-field MRI (4.7 T) was employed here primarily for the proof of principle studies, whereas low-field MRI relying on SLIC polarization transfer [2,3,4,7] will enjoy much longer lived propane singlet states for actual clinical applications at magnetic fields of up to 0.4 T [7]. Furthermore, we explore a possibility of preparation of HP propane gas from cyclopropane, which may be more biologically compatible because of its known prior use as an anesthetic gas. Unlike in case of propylene (Figure 1a), pairwise hydrogenation of cyclopropane can yield two products (Figures 1a,b): 1,2-addition and 1,3-addition. While the conversion of propylene in our clinical-scale hyperpolarizer in >99%, the conversion of cyclopropane is ~2% or below, and our ongoing work on scaling up the catalyst load may improve the percentage conversion.

CONCLUSION: The production of pure (from catalyst) HP propane gas was demonstrated on a clinically relevant scale: ~0.5 L in ~2.0 s (i.e. time which is significantly shorter than T1 relaxation constant at low magnetic fields [7]. This production speed may potentially enable high-throughput clinical scanning of tens of patients per hour on already available clinical MRI scanners and MRI sequences. Production of HP propane from cyclopropane may be more biologically compatible and yield better degree of propane hyperpolarization. ACKNOWLEDGMENTS: NSF CHE-1416268, DOD W81XWH-12-1-0159/BC112431, W81XWH-15-1-0271. REFERENCES: (1) D. A. Barskiy, et al. Chem. Eur. J., 2017, 23, 725. (2) K. V. Kovtunov, et al. Chem. Eur. J., 2014, 20, 14629. (3) Kovtunov, et al. Chem. Eur. J., 2014, 20, 11636. (4) S. J. DeVience, et al. Phys. Rev. Lett., 2013, 111, 173002. (5) D. A. Barskiy, et al. J. Phys. Chem. C, 2017, 121, 10038. (6) K. V. Kovtunov, et al. J. Phys. Chem. C, 2014, 118, 28234. (7) D. A. Barskiy, et al. JMR, 2017, 276, 78.

Figure 1. (a) Reaction scheme of propylene conversion to HP propane gas; (b) Reaction scheme of cyclopropane conversion to HP propane gas; (c) Proton MRI of ~56 mL container filled with stopped HP propane gas at 4.7 T; 2D GRE images were acquired every ~0.5 sec, 256x256 matrix with TR ~ 7 ms.

Pseudorotaxanes as a potential molecular scaffold for 129Xe-MRI

Ashvin Fernando, Francis T. Hane, Braedan R. J. Prete, Brianna Peloquin, Simrun Chahal, Yurii Shepelytskyi, Alanna Wade, Tao Li, Brenton DeBoef and Mitchell S. Albert

Background. Hyperpolarized (HP) Xe gas can be inhaled, and its biodistribution can be imaged using an MRI instrument with a broadband coil. HP Xe atoms cannot, by themselves, be tuned to target particular regions in the body, but targeted HP Xe biosensors that are capable of binding both biochemical receptors and xenon atoms in vivo have been postulated as a new molecular imaging platform.1 The major problem with this technique is that the design and synthesis of the Xe-binding molecular platform is tedious and low yielding. Herein, we report an easily synthesizable pseudorotaxane-based molecular platform for the development of HP-Xe biosensors.

Methods. Pseudorotaxanes are a class of molecules that consists of a macrocyclic host and a linear guest that reversibly form a supramolecular complex. We have used cyclodextrins (CDs) as our choice of host due to their non-toxic and hydrophilic properties. γ-CD, in particular, has been used in this research with an imidazolium-terminated hydrocarbon chain as the guest molecule. The association constants for these complexes were obtained using 1H-NMR based titrations and isothermal calorimetry. Computational modelling was used to predict the free cavity volume after pseudorotaxane formation. HP Xe studies were then performed using a custom-built fritted phantom inside a custom dual-tuned 1H/129Xe radiofrequency (RF) coil.

Results and Conclusions. The pseudorotaxanes formed with association constants of approximately 103 M-1 in water and 102 M-1 in bovine plasma. The pseud-rotaxane with a 10-carbon guest produced a HyperCEST depletion 52%. This is comparable to the HyperCEST depletion of the widely-used molecular cage, cucurbit[6]uril. Our data does not probe a wide range of host–guest association constants, but it appears that an affinity on the order of 103 and an internal hydrophobic cavity with a volume of approximately 164–176 Å3 is sufficient to construct a Xe-binding motif.2 We conclude that with proper optimizations and synthesis the pseudorotaxanes can be functionalized with an affinity tag that can be used to monitor and detect a disease of choice by HP-Xe MRI.

Sources of Funding. The work was supported by the Rhode Island Research Alliance, Bright Focus, and Canadian Institutes for Health Research (CIHR) postdoctoral fellowships to F.T.H. F.T.H. wishes to acknowledge the generous support of the donors of the Alzheimer’s Disease Research, a program of Bright Focus Foundation, for their support of this research. M.A. is supported by a Natural Sciences and Engineering Research Council (NSERC) Discovery grant.

Figure. From Left to R, Energy minimized (PM3 level) molecular model of psueudorotaxane, space filling model of the pseudorotaxane, HyperCEST depletion of diagram of the pseudorotaxne

References

(1) Spence, M. M.; Rubin, S. M.; Dimitrov, I. E.; Ruiz, E. J.; Wemmer, D. E.; Pines, A.; Yao, S. Q.; Tian, F.; Schultz, P. G. Proc. Natl. Acad. Sci. 2001, 98 (19), 10654.

(2) Hane, F. T.; Fernando, A.; Prete, B. R. J.; Peloquin, B.; Karas, S.; Chaudhuri, S.; Chahal, S.; Shepelytskyi, Y.; Wade, A.; Li, T.; Deboef, B.; Albert, M. S. ACS Omega 2018, 3 (1), 677.

In-situ rotational Raman spectroscopy mapping internal gas temperatures in tandem with Atomic absorption spectroscopy to measure Rb Vapour density in various gas mixes

during Xe129 SEOP

Robert K. Irwin1 ,James W. Harkin1, Jonathan Birchall1, Boyd M. Goodson2 and Michael J.Barlow1

1. Sir Peter Mansfield Imaging Centre, University of Nottingham, Nottingham UK 2. Dept. of Chemistry & Biochemistry, Southern Illinois University Carbondale, Illinois, USA

Background: The field of hyperpolarized MRI imaging with 129Xe has made great advances in recent years with dramatic increases in 129Xe polarization and improved production rates of the gas administered to patients [1]. Despite this progress, further improvements are desired to support a number of applications including large clinical pulmonary studies. Significant production gains are anticipated with a better understanding of the underlying SEOP dynamics and processes; particularly when performed at clinical production rates. Method: Data was recorded for a xenon-rich gas mixes with Nitrogen acting as a buffer gas to inhibit radiation trapping, while also providing the Raman signal In situ Raman spectroscopy was used to measure internal gas temperatures within SEOP cells by probing the rotational temperature of N2 buffer gas [2]. 129Xe polarization was measured in tandem via low-field NMR. The 129Xe polarization and gas temperature were measured along the path of the D1 pump laser beam during SEOP, under a range of cell temperatures and Xe/N2 buffer mixes. [3]. Using a programmable linear transition stage to move the Raman sampling head allowing the internal temperature to be mapped across different locations within the cell. [4]. This gives us a clearer picture both temporally and spatially of local cell gas temperature changes throughout a given run of a stopped-flow SEOP system.. Atomic absorption spectroscopy was performed using a broadband source probing the Rb D2 line. This is the first time AAS has been used in tandem with Raman spectroscopy on 129Xe SEOP. Knowing how the Rb density varies during SEOP will also provide further information into understanding the underlying SEOP dynamics. By using localized NMR and Raman spectroscopy it was possible to demonstrate how the Xe/Nitrogen buffer gas mix and initial alkali metal vapor density affects local gas temperature, 129Xe polarization and Rb vapor density throughout the cell volume over time. Results: Raman spectroscopy showed that at lower oven temperatures the temperature was uniform along the cell with a gas temperature slightly above oven temperature. Higher oven temperatures resulted in a much higher Rb gas temperature. Gas up to 200C above the oven was seen. Also, higher oven temperatures resulted in a temperature gradient along the cell. With higher temperatures at the front reducing towards the back. This is from the shadowing effect of the laser light by high a Rb vapor density reducing the laser transmission to the rear of the cell. Higher oven temperatures resulted in an increased Rb vapor density, however as the cell ages, Rb condenses on the walls of the cell. This gave rise to an increased alkali metal density in experiments with the same starting conditions performed on consecutive days. Therefore AAS can also be used to improve the comparability of our data. See Figure 1. This data has improved our understanding of how different buffer gas mixes affects energy transport within the optical cell. This should lead to the optimized production of hyperpolarized 129Xe via stopped-flow SEOP. Yielding the highest polarization possible, or achieving the desired polarization in a shorter amount of time Future work: The hope is to also use this method to look at ratios of Helium to Nitrogen in the buffer gas before XeMAT. Helium has a higher thermal conductivity compared to Nitrogen [5]. It is thought that the higher the ratio of Helium to Nitrogen in the buffer gas the more uniform the temperature of the cell will be. This could reduce the effect of Rubidium runaway in the front of the cell at higher Rb densities as the heating induced by the pump laser will be able to dissipate into the rest of the cell more readily.

Figure 1: A graph to AAS for a single gas mix at different oven temperatures to show difference in relative Rb vapor density for consecutive days as the cell ages.

Sources of Funding: James Tudor Foundation Nottingham University References: [1] “Near-unity nuclear polarization with an open-source 129Xe hyperpolarizer for NMR and MRI” P. Nikolaou, A.M. Coffey, L.L. Walkup, B.M. Gust, N. Whiting, H. Newton, S. Barcus, I. Muradyan, M. Dabaghyan, G.D. Moroz, M.S. Rosen, S. Patz, M.J. Barlow, E.Y. Chekmenev, and B.M. Goodson. Proc. Natl. Acad. Sci. USA 110 (35) 14150-14155 (2013) [2] “Rotational Raman scattering in the instructional laboratory” A. Compaan, A Wagoner and A Aydinli. Am J. Phys 62 (7) 639-645 (1994) [3] “Comparative study of in situ N2 rotational Raman spectroscopy methods for probing energy thermalisation processes during spin-exchange optical pumping.” H. Newton, L. L. Walkup, N. Whiting, L. West, J. Carriere, F. Havermeyer, L. Ho, P. Morris, B.M. Goodson • M.J. Barlow, Appl. Phys. B DOI - 10.1007/s00340-013-5588-x (online) 2013 [4] "Observing and preventing rubidium runaway in a direct-infusion xenon-spin hyperpolarizer optimized for high-resolution hyper-CEST (chemical exchange saturation transfer using hyperpolarized nuclei) NMR." Witte, C., Kunth, M., Rossella, F., & Schröder, L., The Journal of chemical physics 140.8 084203. (2014) [5] https://www.engineersedge.com/heat_transfer/thermal-conductivity-gases.htm

Quantitative Detection of Alveolar Morphometric Changes in Smokers with 129Xe MRI

Huiting zhang, Haidong Li, Junshuai Xie, Xiuchao Zhao, Xianping Sun, Chaohui Ye, Xin Zhou*

State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, National Center for Magnetic

Resonance in Wuhan, Wuhan Institute of Physics and Mathematics, Chinese Academy of Sciences, Wuhan,

430071, P. R. China

Purpose: To quantitatively detect early microstructural changes of current smokers with hyperpolarized (HP) 129Xe MRI and compare the lung morphometric results with the pulmonary function test (PFT).

Methods: All the subjects (43-68 yrs old) with a smoking history of ≥10 pack-year were assigned three groups

on the basis of the FEV1/FVC ratio and with and without emphysema: the healthy (HN) group (n=8), the

FEV1/FVC ratio ≥ 70% and without emphysema; the asymptomatic (AS) group (n=5), the FEV1/FVC ratio ≥ 70%

and with emphysema; the chronic obstructive pulmonary disease (COPD) group (n=11), the FEV1/FVC ratio <

70%. The morphometric parameters were obtained using the cylindrical model1. Pearson correlation coefficients

were used to assess the correlation between MR imaging and PFT parameters. Analysis of variance (ANOVA)

was also performed to calculate the differences among the groups.

Results and Discussion: Significant positive correlation between DLco/VA and h (Pearson coefficient r=0.82,

p<0.001) was found, which was the first reported (Figure 1A). However, there was no significant correlation

between DLco and h (not shown). The possible reason is DLco reflects the diffusion capacity of the whole lung

and affected by the distribution of ventilation (the number of alveoli and the size of alveolar spaces), and

DLco/VA reflects the pathology at the level of the alveolocapillary membrane2. Figure 1B shows the

comparisons of h for the three groups, and significant differences was found among the groups (healthy

smokers and asymptomatic smokers, p=0.012; asymptomatic smokers and smokers with COPD, p=0.003;

healthy smokers and smokers with COPD, p<0.001). The results shows that the parameter h can be used to

discriminate all three groups and it may be helpful in diagnosing early emphysema.

Conclusions: Hyperpolarized 129Xe lung morphometry is a sensitive noninvasive method for measuring acinar

geometry, and it will benefit the diagnosis of early emphysema.

References: 1. Sukstanskii AL, Yablonskiy DA. Magn. Reson. Med. 2012; 67: 856-866. 2. Ayers LN, Ginsberg

ML, Fein J, Wasserman K. West J Med. 1975; 123: 255-264.

ACKNOWLEDGEMENTS: This work was funded by the National Natural Science Foundation of China

(81227902, 81625011). National Program for Support of Eminent Professionals (National Program for Support

of Top-notch Young Professionals).

Fig.1 (A) Scatterplot showed linear regression for DLco/VA percentage predicted with alveolar depth h in all

subjects; (B) Boxplots showed h in all subjects from three groups, *p<0.05; **p<0.01; ***p<0.001.

Passive Up-Concentration of a Continuous Hyperpolarized 129Xe Gas Stream

Wolfgang Kiliana, Sergey Korchaka, Lorenz Mitschanga and Jan Windb

a) Physikalisch-Technische Bundesanstalt (PTB), 12355 Berlin, GERMANY (lorenz.mitschang@ptb.de)

b) Helmholtz-Zentrum Geesthacht, Geesthacht, Germany

The use of hyperpolarized 129Xe (hyp-Xe) for MR measurements has found an ever-increasing interest (1, 2). However, only

a view sites have managed to transfer those applications to in-vivo measurements up to now due to the complicated

technique necessary to be implemented to achieve animal ventilation. One approach to overcome the use of the freeze-

thaw technique together with a dedicated ventilator was recently demonstrated (3). However, an active compressor had to

be used yielding a hyp-Xe gas stream at atmospheric pressure. Other groups used flammable buffer gases and removed

those ether by combustion (4) or freezing (5), somehow hard to approve the safety for animal studies.

Here, we demonstrate the application of a complete passive system utilizing a semipermeable membrane (6) to separate the gross amount of process gas, namely helium from the hyperpolarized gas stream produced by a hyp-Xe polarizer (7) working at the usual pressure conditions (Fig. 1). The gas flow at the inlet of the polarizer was 1.29 ml/min, 12.9 ml/min and 179.5 ml/min (referred to normal conditions) for Xe, N2 and He, respectively. The total gas pressure was kept at 3 bar. The amount of helium extraction is adjusted by regulating the permeate pressure via a needle valve before a vacuum pump.

To disentangle the aimed effect of helium extraction and the unwanted effect of polarization loss we used a rather complex

but well understood system (8). By bubbling the gas leaving the membrane module into a water sample containing

cryptophane-A cage at a relatively high concentration [CrA] ≈ 10 𝜇M one detects the two well separated spectral lines for

free and cage-bound xenon of amplitudes 𝑆169 = 𝑎 𝑃𝑋𝑒 𝑠 𝑝𝑋𝑒 and 𝑆64 = 𝑎 𝑃𝑋𝑒 [𝐶𝑟𝐴]𝐾 𝑠 𝑝𝑋𝑒

1+𝐾 𝑠 𝑝𝑋𝑒, respectively. Here is 𝑃𝑋𝑒 the

129Xe nuclear polarization and 𝑝𝑋𝑒 the xenon partial pressure within the gas coming from the membrane module. The

complex association constant 𝐾 = 58400 M−1 was determined independently while 𝑎 is an instrumentation dependent

constant scaling factor. Using the xenon solubility 𝑠 = 0.00432 M/bar one can determine the xenon partial pressure from the

ratio of the two signal intensities 𝑝𝑋𝑒 = [CrA]

𝑠

𝑆196

𝑆64−

1

𝐾𝑠 as shown in Fig. 2.

For each xenon feed pressure an increase in the free xenon signal S196 of 2.5 at most was seen showing a gain in hyp-Xe

signal behind the module. Overall one can conclude that the up-concentration works for a wide range of xenon feed partial

pressure and can be adjusted for the optimum condition for the application in mind.

This work was funded by EURAMET and the European Union (EMRP grant HLT-10) and by the German Science Foundation (TRR 67-A2).

References:

(1) T. Meersmann & E. Brunner (Eds.); Hyperpolarized Xenon-129 Magnetic Resonance; The Royal Society of Chemistry, 2015

(2) M. S. Abert & F. T. Hane (Eds.); Hyperpolarized and Inert Gas MRI; ACADEMIC PRESS, 2017 (3) I. Hirohiko, A. Kimura, H. Fujiwara; Magn Reson Anal Sci, 2014, 30, 157-166 (4) Stupic KF, et al. Phys.Chem.Chem.Pyhs., 2013, 15, 94 (5) Imai H, et al. Sci. Rep. 2017, 7, 7352 (6) T. Brinkmann, J. Pohlmann, U. Withalm, J. Wind & T. Wolff; Chem lng Tech, 2013, 85, 1210-1220 (7) S. Korchak, W. Kilian & L. Mitschang; Appl Magn Reson, 2013, 44, 65-80 (8) S. Korchak S, W. Kilian, L. Schroder & L. Mitschang; Mag Reson. 2016, 139-145

Figure 2: Calculated xenon partial pressures in the retentate gas stream as calculated from the S169/S64 ratio.

Figure 1: Experimental setup: a) normal gas separation module; b) special non-metallic module; c) picture of setup at the spectrometer; d) scheme of the gas flow setup.

Reorientation jumps and energy profile for Xe diffusing from site to site along the channels of porous molecular crystals M. Negroni, S. Bracco, A. Comotti, C. Bezuidenhout, I. Bassanetti, L. Marchio’ and P. Sozzani Department of Materials Science, Milano-Bicocca University, via R. Cozzi 55, 20125 Milan, Italy and Department SCVSA, Parma University, via delle Scienze 17/a, 43124 Parma, Italy. m.negroni2@campus.unimib.it The sensitivity of 129Xe NMR to the size and shape of the cavities makes, both thermally-polarized and hyper-polarized techniques, invaluable for the characterization of porous materials, such as MOFs and molecular crystals [1-2]. In this presentation, the chemical shift anisotropy (CSA) pattern mirrors not only shape and symmetry of the explored rooms, but also the dynamics of xenon jumping from one site to the next. This study belongs to a program for generating ultra-fast molecular rotors and understanding dynamics in porous crystals [3-4]. Tetra-carboxylic molecules could be obtained in the permanently porous form for the stability imparted by 8 hydrogen bonds: the material was explored by xenon and the anisotropic 129Xe signal resonates in the 220-320 ppm range, indicating a tight fit of the gas atom in the adsorption sites [5]. The intriguing line-shape evolution (see figure) denotes a temperature dependent exchange dynamics (observed at 10 bar

loading pressure) and was interpreted as the effect of thermally activated Xe jumps to adjacent vacant sites along the channels. Each site is marked by the relative orientations. Indeed, the explored cavities show elliptical cross-sections (e = 0.75), alternatively rotated by 90° about the channel axis, as CSA profile below 240 K depicts. At higher temperatures, xenon atoms dynamically explore the two orientations and, when the exchange rates exceed the frequency span of the tensor principal components, Xe perceives an averaged interaction. This interpretation allowed us to simulate the anisotropy and assign at each pattern a specific jump-rate and to measure, by an Arrhenius plot, the energy barrier for an individual jump of 1.8 kcal/mol. Ab initio calculations and molecular dynamics confirm the high mobility of xenon atoms inside the structure and evaluate a consistent energy barrier. The experimental single-jump frequency and energy were the basis to establish xenon diffusion rate in the narrow channels. Source of founding PRIN 2017-20 -NAZ-104, Cariplo Foundation 2017-19 BALANCE and INSTM-Lombardy 2017-18. References: [1] Porous Materials Explored by Hyperpolarized Xenon NMR; P. Sozzani, S. Bracco, A. Comotti in Hyperpolarized Xenon-129 Magnetic Resonance T. Meersman and E. Brunner (Eds.), 2015, 164. [2] A. Comotti, S. Bracco, P. Sozzani, S. Horike, R. Matsuda, S. Kitagawa JACS, 2008, 130,13664. [3] Review: Molecular rotors build in porous materials; S. Bracco, A. Comotti, P. Sozzani, Acc. Chem. Res., 2016, 49, 1701. [4] S. Bracco, F. Castiglioni, A. Comotti, S. Galli, M. Negroni, A. Maspero, P. Sozzani, Chem. Eur. J., 2017, 23, 11210. [5] I. Bassanetti, S. Bracco, A. Comotti, M. Negroni, C. Bezuidenhout, S. Canossa, P. P. Mazzeo, L. Marchio’, P. Sozzani J Mater. Chem A (in press).

Genetically Encoded Contrast Agents for Hyperpolarized Xenon NMR Benjamin W. Roose†*, Serge D. Zemerov†, Yanfei Wang†, Vincenzo Carnevale‡, Ivan J. Dmochowski†

† Department of Chemistry, University of Pennsylvania, Philadelphia, PA 19104 ‡ Institute for Computational Molecular Science, Temple University, Philadelphia, PA 19122 * roose@sas.upenn.edu

Background Genetically encoded (GE) fluorescent contrast agents such as green fluorescent protein (GFP) have enabled biomolecular imaging for optically transparent samples, but few analogs exist for magnetic resonance (MR) spectroscopy or imaging. Methods MR contrast from GE contrast agents is measured by chemical exchange saturation transfer (CEST) using hyperpolarized (hp) 129Xe. Xenon binding to GE contrast agents is further characterized by X-ray crystallography, molecular dynamics simulations, and site-directed mutagenesis studies. Results Our group has demonstrated that the bacterial enzyme TEM-1 β-lactamase (TEM1) is a viable GE contrast agent for hp 129Xe NMR. Hyper-CEST experiments with TEM1 reveal a unique saturation peak ~60 ppm downfield of the 129Xe-H2O peak, allowing nanomolar TEM1 to be detected in mammalian cells. Additionally, we have identified maltose binding protein (MBP) as an analyte-responsive GE contrast agent. MBP consists of two globular domains that transition from an “open” to “closed” conformation upon binding maltose. MBP generates 129Xe hyper-CEST contrast that is proportional to the amount of MBP in its closed conformation, allowing nM-to-mM concentrations of maltose to be quantified using only 100 nM MBP. Conclusions Monomeric bacterial proteins such as TEM1 and MBP constitute a new platform for developing GE contrast agents detectable by hyperpolarized Xe NMR and MRI. Funding sources

• NIH grant R01-GM097478 • CDMRP-LCRP concept award no. LC130824

References

1. Roose, B. W.; Zemerov, S. D.; Dmochowski, I. J. Chem. Sci. 2017, 8, 7631–7636. 2. Wang, Y.; Roose, B. W.; Palovcak, E. J.; Carnevale, V.; Dmochowski, I. J. Angew. Chem. Int.

Ed. Engl. 2016, 55, 8984–8987.

Pseudomorphic transformation of biogenic silica from spelt husk and characterization

using continuous-flow hyperpolarized 129Xe- NMR

M. Wenzel*,1, D. Schneider2, S. Wassersleben2, J. Hollenbach1,3, J. Matysik1, D. Enke2

1Institut für Analytische Chemie, Universität Leipzig, Linnéstr. 3, 04104 Leipzig, Germany 2Institut für Technische Chemie, Universität Leipzig, Linnéstr. 3, 04104 Leipzig, Germany 3University of Southampton, University Road, Southampton, United Kingdom *E-mail: marianne.wenzel@uni-leipzig.de

In times of increasing environmental awareness in industry and research, the view widens

towards sustainable solutions and recycling strategies for local and regional agricultural waste

with economic benefits. Since plants accumulate silicon from soil as a physical protective

structural component inside their cell walls, this gives rise to numerous potential applications

for ubiquitous biogenic silica [1]. The need for silica-based materials with large specific surface

areas and well-defined porous structures is consistently high, for example as carrier materials

for catalysts [2]. Biogenic silica can be obtained by a chemical and thermal treatment of

crushed plants or parts of plants leaving a white ash behind that consists mainly of SiO2. For

example, spelt husk ash consists of 98 wt% SiO2 whose properties were investigated in this

study.

It provides a starting material for pseudomorphic transformation, a method that allows to

introduce a highly ordered porous structure to amorphous silica while maintaining the

macroscopic shape and therefore recently became state of the art in material sciences [3]. A

series of experiments using cetyltrimethylammonium-based surfactants in alkaline milieu has

been performed aiming to investigate the influence of various counterions and to test a novel

microwave synthesis route as an efficient and timesaving alternative for conventional methods.

The resulting material showed highly ordered mesopores with similarity to MCM-41 materials

and increased BET-surface areas. The characterization of the porous structure of the

innovative biogenic silica was conducted by hyperpolarized-129Xe-NMR spectroscopy under

continuous flow [4]. For comparison, established methods like nitrogen absorption and x-ray

diffraction were performed as well. It became clear that continuous-flow

hyperpolarized-129Xe-NMR spectroscopy provides qualitative results in good consistence with

the classical methods although the quantification remains difficult and will be subject of further

studies.

References

[1] H. A. Currie and C. C. Perry, Ann. Bot. 100 (2007) 1383–1389.

[2] L. Puppe, Chemie in unserer Zeit 20 (1986) 117–127.

[3] B. A. Galarneau et al., Adv. Funct. Mater. 16 (2006) 1657–1667.

[4] J. Hollenbach, Dissertation, Universität Leipzig (2017).

A New Photosensitive Hyperpolarized 129Xe NMR Biosensor

Longhui Zhaoa,b，Qianni Guoa,b，Bin Zhanga，Yaping Yuana,b，Maili Liua,b，Xin Zhou*a,b

a State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, National Center for Magnetic

Resonance in Wuhan, Wuhan Institute of Physics and Mathematics, Chinese Academy of Sciences, Wuhan, 430071, P. R.

China; bUniversity of Chinese Academy of Sciences, Beijing 100049, People’s Republic of China.

Recently, the development of hyperpolarized 129Xe NMR and MRI biosensors have been applied to the detection of

peptides, proteins, thiols[1] , metal ions[2], and enzyme activity due to its high sensitivity and low detection limit compared

with the 1H MRI. It focused on modifying organic host molecules (e.g., cryptophanes) via diverse conjugation chemistry and

acquired numerous sensing applications.

We developed a 129Xe biosensor by combining cryptophane-A with riboflavin moiety, which expanded the application of

129Xe bosensors. Since riboflavin (vitamin B2) and its derivatives are photosensitive and closely related to life activities, this

new 129Xe biosensor has some photosensitive properties. As showed in Figure 1, When irreversible photolysis take place

after irradiation, the structure of the biosensor is changed (Figure 1 (a)), the UV-vis absorbance of it decreases with time

(Figure 1 (b)), and the chemical shift of the caged Xe changes downfield for 5.3 ppm. This change suggests that the

riboflavin glycosyl chain in the 129Xe biosensor breaks down after photolysis and the molecular structure of the 129Xe

biosensor becomes different. At the same time the glycosyl chain breaking down leads to the UV-Visabsorption blue shift

and decreasing, which trends consistent with the previously reported[3].

Figure 1. Photolysis of biosensor 1: (a) the mechanism of photolysis; (b) UV-vis absorbance spectra (A=100 μM), and (c)

129Xe NMR Spectra (A=50 μM, ns=64), 20 mM phosphate buffer; pH=7.4; 40% DMSO; 250 W high-voltage mercury lamp

with emission at 350~450nm, t=0~3.5 h.

We developed a new biosensor successfully by connecting cryptophane-A and riboflavin together. 129Xe NMR and optical

spectroscopy characterization confirmed that the CrA-RF had a good photosensitive properties via 129Xe NMR and

fluorescence spectroscopy.

References

[1] Qingbin Zeng, Xin Zhou, et al, Anal. Chem., 2017, 89: 2288-2295.[2] Qianni Guo, Xin Zhou, et al, Chem.- Eur. J., 2016,

22: 3967-3970. [3] Iqbal Ahmad, Adnan Noor, et al, J. Photoch. Photobio B, 2004, 75: 13-20.

ACKNOWLEDGEMENTS

This work was funded by the National Natural Science Foundation of China (81227902, 81625011), National Program for

Support of Eminent Professionals (National Program for Support of Top-notch Young Professionals)