Bargon, Joachim: ChanceDiscoveries ofHyperpolarizationPhenomena

Joachim BargonUniversity of Bonn, Bonn, Germany

CHEMICALLY INDUCED DYNAMIC NUCLEAR

POLARIZATION (CIDNP)

Chance discoveries may advance science more than manycarefully designed experiments. Accordingly, hyperpolariza-tion phenomena in magnetic resonance1 initially emerged byaccident – even on more than one occasion: one such caseoccurred in Darmstadt, Germany, in 1965 (Figure 1) duringmy PhD thesis, when I was investigating polymerization reac-tions in situ, i.e., within an NMR spectrometer.2,3 WheneverI initiated the polymerization of the simple monomer maleicanhydride using free radicals, very intense absorption lines –likewise, some with “inverted phase,” possibly emission lines– appeared immediately upon the onset of the reactions. If, bycontrast, I initiated the polymerization ionically, using pyri-dine, no such phenomena occurred.

The only seemingly related phenomenon known to meat that time was “dynamic nuclear polarization (DNP),”based upon the Overhauser effect.4 Informed of my results,Prof. Rex E. Richards from Oxford University suggestednaming the new phenomenon chemically induced dynamicnuclear polarization (CIDNP) because he too thought that herethe DNP-like enhanced absorption and emission lines were“chemically induced” rather than by microwave irradiationof a system containing paramagnetic centers.3 In DNPexperiments, however, the latter are typically stable freeradicals, and microwave irradiation causes such systemsto become “saturated,” whereupon equal numbers of spinsoccupy the upper and lower energy levels of the stable freeradicals, between which resonance transitions are induced.

Our initially proposed DNP-based interpretation of CIDNP,which was encouraged by Prof. Richards, implied that therupture of a chemical single bond, containing two electronswith antiparallel spins before rupture, would likewise resultin a “saturated” electron spin system.5 Ensuing relaxationphenomena would yield results resembling DNP in the NMRspectra, but in case of CIDNP these phenomena were causedby the intermediate occurrence of unstable, even short-livedfree radicals.

When we presented our results at the Gordon ResearchConference on Magnetic Resonance in 1967, at Providence,Rhode Island, USA, Ward and Lawler informed us thatthey had observed essentially similar phenomena in situ,namely, during the reactions of organic lithium compoundswith organic halides.6 Thereupon, accepting the DNP-basedexplanation of CIDNP, these authors concluded that the

observed CIDNP phenomenon yielded proof of the occurrenceof free radicals in their reaction scheme.7

The DNP-based theory, however, could not explain allexperimentally observed features. The true basis of the CIDNPphenomenon remained a puzzle until 1969, when again twoteams, Kaptein and Oosterhoff at Leiden (the Netherlands),8

and Closs at Chicago (USA),9 virtually simultaneously foundthe correct interpretation, namely, the “radical pair (RP)theory of CIDNP.” Their RP-based explanation of CIDNPtook care of all previously unresolved problems, and for thefollowing ten years the observation of CIDNP was acceptedas unequivocal evidence for the occurrence of free radicalsduring chemical reactions.10

THE “MONDAY EFFECT”: PARAHYDROGEN-

INDUCED POLARIZATION (PHIP)

In 1979, however, following my seminar at the Universityof California, Berkeley, on “Applications of the CIDNP inPhysical Organic Chemistry,” Prof. Robert Bergman asked,“How come we observe the CIDNP phenomenon at Berkeleyonly on Monday in the morning?” Since even time-dependentphenomena do not depend on the day of the week, this remarkidentified a new challenge: As a consequence of the energycrisis at that time, Prof. Bergman had assigned his graduatestudent Henry Bryndza to reinvestigate the Fischer–Tropschreaction, used to liquefy coal via hydrogenation. Therefore,Henry Bryndza explored the hydrogenation reactions ofsimple model compounds, that is, of bi- and trinuclearcobalt–acetylene complexes.11 These reactions had to bestudied at 60 ◦C. Since Henry used the department-ownedmachine, which was operated in a self-service mode, otherusers disliked his “high-temperature studies” since they haddifficulties shimming the spectrometer after he used it.Therefore, poor Henry could only use the spectrometer at thevery end of a weekend, i.e., in the early morning hours ofMondays, when the NMR spectra of all other samples had beenrecorded. To utilize his assigned time most efficiently, Henryprepared his samples in advance on a Friday, adding a solventto the organometallic model compounds and charging thesamples with 3 bar of hydrogen gas. Thereupon, he immersedthe sample tubes into liquid nitrogen and kept them in aDewar, ready to be inserted into the preheated probe of theNMR spectrometer on Monday morning. No one suspectedthat the liquid nitrogen storage was the “culprit” that causedthe “Monday phenomenon”!

Collaborating thereupon, we could not repeat the exper-iment at other locations on any day of the week. Worse,even on using a time-proven simulation program for CIDNPspectra, we could not get any matching results, no mat-ter what unusual free radicals we assumed as intermediates.Yet the results were very interesting, intriguing, but unex-plained in detail.12 Nevertheless, when writing up his thesis,Henry and other coworkers wanted to publish their obser-vations, and – following the then “established” concept10

– they took the occurrence of this “pseudo-CIDNP” (laterrecognized to be parahydrogen-induced polarization, PHIP) assupposed evidence for the occurrence of free radicals duringorganometallic hydrogenation reactions.13

This puzzle remained unresolved until the Gordon ResearchConference on Magnetic Resonance in 1987. There, during

eMagRes, Online © 2007 John Wiley & Sons, Ltd.This article is © 2010 John Wiley & Sons, Ltd.This article was previously published in the Encyclopedia of Magnetic Resonance in 2010 by John Wiley & Sons, Ltd.DOI: 10.1002/9780470034590.emrhp1003

2 JOACHIM BARGON

Figure 1 The first observation of CIDNP at the Technical Universityof Darmstadt, Germany, in 1965 during the polymerization of maleicanhydride using free radical polymerization initiators within a VarianDP 60 NMR spectrometer

an evening session, Prof. Daniel Weitekamp of CALTECH,Pasadena, USA, talked about a “Gedankenexperiment,” theconcept and the expected results thereof he had already pub-lished in Physical Review Letters.14 During his presentation, itimmediately became obvious both to me and to Prof. Lawler,who was also there, that Weitekamp’s “PASADENA effect”allowing laser-type transitions upon breaking the symmetryof parahydrogen via a chemical reaction provided the stillmissing theoretical explanation of Henry Bryndza’s “Mon-day phenomenon”: Henry’s storage of his samples in liquidnitrogen had converted the molecular hydrogen into parahy-drogen aided by the organometallic additive to an extent thatwas sufficient to give rise to parahydrogen-induced polariza-tion, as this phenomenon was called subsequently by us andothers.15 Daniel Weitekamp had independently conceived the“PASADENA effect” that Henry Bryndza had observed byaccident.

At present, all three phenomena, namely, DNP,4 CIDNP,16

and PHIP,17 are utilized as valuable means to achieve“hyperpolarization,” boosting the otherwise low sensitivity ofNMR transitions for use in medical, chemical, and biologicalapplications.18 – 21

REFERENCES

1. Wikipedia, Hyperpolarization (physics), from Wikipedia Online,date accessed, July 18, 2010, http://en.wikipedia.org/wiki/ Hyper-polarization (physics)

2. J. Bargon, H. Fischer, and U. Johnsen, Z. Natorforsch., 1967, 22a,1551.

3. J. Bargon, Helv. Chim. Acta , 2006, 89, 2082.

4. Wikipedia, Dynamic Nuclear Polarization, from Wikipedia On-line, date accessed, July 18, 2010, http://en.wikipedia.org/wiki/Dynamic nuclear polarisation

5. J. Bargon and H. Fischer, Z. Naturforsch., 1967, 22a, 1556.

6. H. R. Ward and R. G. Lawler, J. Am. Chem. Soc., 1967, 89, 5518.

7. CIDNP, Chem. Eng. News 1968, January 15, p 40.

8. (a) R. Kaptein and L. J. Oosterhoff, Chem. Phys. Lett., 1969, 4,195; (b) ibid. 1969, 4, 214.

9. (a) G. L. Closs J. Am. Chem. Soc., 1969, 91, 4552; (b) G. L.Closs and A. D. Trifunac, ibid., 1969, 91, 4554.

10. (a) R. Kaptein, Adv. Free Rad. Chem., 1975, 5 319; (b)Plenum: New York, 1982, vol. 4, p 145; (c) G. L. Closs, Adv.Magn. Res. 1974, 7, 157; (d) L. T. Muus, P. W. Atkins, K.A. McLauchlan, and J. B. Pedersen eds, ‘Chemically InducedMagnetic Polarisation’, D. Reidel: Dordrecht, 1977.

11. Britannica, Fischer-Tropsch Reaction, from Encyclopædia Britan-nica Online, date accessed, July 18, 2010, http://www.britannica.com/EBchecked/topic/208441/Fischer-Tropsch-reaction

12. H. E. Bryndza, R. G. Bergman, J. Bargon, and H. E. Bryndza,PhD thesis, University of California Berkeley: Berkeley, California,1981, Chapter V, p 75.

13. (a) A. H. Janowicz, H. E. Bryndza, and R. G. Bergman, J. Am.Chem. Soc. 1981, 103, 1516; (b) P. F. Seidler, H. E. Bryndza,J. E. Frommer, L. S. Stuhl, and R. G. Bergman, Organometallics ,1983, 2, 1701.

14. (a) C. R. Bowers and D. P. Weitekamp, Phys. Rev. Lett. 1986, 57,2645; (b) C. R. Bowers and D. P. Weitekamp, J. Am. Chem. Soc.1987, 109, 5541.

15. T. C. Eisenschmid, R. U. Kirss, P. P. Deutsch, S. I. Hommeltoft,R. Eisenberg, J. Bargon, R. G. Lawler, and A. L. Balch, J. Am.Chem. Soc., 1987, 109, 8089.

16. Wikipedia, ‘CIDNP’ (Chemically Induced Dynamic NuclearPolarization), from Wikipedia Online, date accessed, July 18,2010, http://en.wikipedia.org/wiki/Dynamic nuclear polarisation,http://en.wikipedia.org/wiki/CIDNP

17. J. Natterer and J. Bargon, Prog. Nucl. Magn. Res. Spectr.,1973, 31, 293, http://www.brookhaventech.com/pdf/ Parahydro-gen%20induced%20polarization.pdf date accessed, July 18, 2010.

18. K. Golman, O. Axelsson, H. Johannesson, S. Mansson, C.Olofsson, and J. S. Petersson, Mag. Res. Med., 2001, 46, 1.

19. J. H. Ardenkjaer-Larsen, K. Golman, A. Gram, M. H. Lerche,R. Servin, M. Thaning, and J. Wolber, PNAS , 2003, 100, 10158,published online August 20, 2003, doi: 10.1073/pnas.1733835100;Discovery Medicine, 2009, date accessed, July 18, 2010,http://www.discoverymedicine.com/Jan-H-Ardenkjaer-Larsen/

20. W. S. Warren, E. Jenista, R. T. Branca, and X. Chen, Science,2009, 323, 1711.

21. M. Levitt and M. H. Levitt, In ‘Encyclopedia in Nuclear MagneticResonance’, eds R. K. Harris and R. E. Wasylishen, JohnWiley & Sons: Chichester, 2010, in print, http://www.mhl.soton.ac.uk/public/Main/index.html, date accessed, July 18, 2010.

Biographical Sketch

Joachim Bargon studied physics at the Technical University ofDarmstadt, Germany. Upon completing his PhD degree under theguidance of Prof K.H. Hellwege and collaborating with Prof HannsFischer there, he joined Prof G.S. Hammond’s group at the CaliforniaInstitute of Technology in Pasadena, California, USA, in 1969, wherehe spent 1 year as a postdoctoral fellow in organic chemistry. Hebecame a research staff member of the IBM Thomas J. Watson ResearchCenter at Yorktown Heights, New York, in 1970, from where hetransferred to the IBM Research Laboratory at San Jose, California,

eMagRes, Online © 2007 John Wiley & Sons, Ltd.This article is © 2010 John Wiley & Sons, Ltd.This article was previously published in the Encyclopedia of Magnetic Resonance in 2010 by John Wiley & Sons, Ltd.DOI: 10.1002/9780470034590.emrhp1003

JOACHIM BARGON 3

in 1971. Having been a Group Manager (1973–1977) and subsequentlya Department Manager (1977–1984) there, he was appointed as afull-time Professor of Physical Chemistry at the University of Bonnin Germany in 1984–2004. He has spent various sabbaticals at theUniversity of California at Berkeley and Santa Barbara, and at the

Federal University of Campinas in Brazil. Since his retirement fromthe University of Bonn, he is associated as a Visiting Scientist withthe University of Pennsylvania in Philadelphia, USA, and with theMax–Planck Institute of Polymers at Mainz, Germany.

eMagRes, Online © 2007 John Wiley & Sons, Ltd.This article is © 2010 John Wiley & Sons, Ltd.This article was previously published in the Encyclopedia of Magnetic Resonance in 2010 by John Wiley & Sons, Ltd.DOI: 10.1002/9780470034590.emrhp1003