Poul Erik Hansen
I was born 1945 in Middelfart, Denmark and attended
chemistry studies at the University of Århus graduating
in 1970 having worked on synthesis of crowded alkyl
polycyclic aromatic hydrocarbons, primarily pyrenes.
The University of Århus acquired it first computer
during my studies, something that really turned me on
and later led to programming of computer programs to
be used in analysis of complex NMR spectra. The source code is the backbone of a commercial
program by Bruker. Furthermore, in 1966 the university received its first NMR spectrometer, a
Varian HA 60. Using this led to a fascination that has followed me ever since. My Ph.D. work was
concentrated on synthesis of specifically 13C labeled polycyclic aromatic hydrocarbons such as 113
C-pyrene in order to measure 13C,13C coupling constants. [1,2] This later inspired Ad Bax to invent
the INADEQUATE sequence. Double labeling in a symmetric fashion like in phthalates enables
determination of relative signs. [3] This technique was later transferred to difluoronaphthalenes.[4]
During my stay as a Royal Society Exchange Fellow at National Institute of Medical Research, Mill
Hill, London the work was concentrated on use of 13C,H coupling constants in conformational
analysis of amino acids [5] work that was later transferred into proteins and led to a review.[6]
During my stay as a postdoc at the university of Alberta, Edmonton, Canada in 1977-78 I was further
engaged in real biological work, using NMR to investigate muscle contraction. After the postdoc
period I got an associate professorship at Roskilde University in 1979. Being a department of
Chemistry and Biology it was natural to continue work on whole cells, in the first instance
erythrocytes [7], exploring the fact that despite the inhomogeneous solution, very useful NMR
spectra could be obtained. Work on specifically labeled cyclobutene led me into isotope effects on
chemical shift research, something that together with hydrogen bonding has been a major research
topic for the last 30 years. In hydrogen bond research both intra and intermolecular hydrogen bonds
can be studied by isotope effects on chemical shifts. Furthermore, a very important topic for
intramolecularly hydrogen bonded compounds is the possible existence of tautomerism. An eye
opener was the investigation of -thioxoketones revealing deuterium equilibrium isotope effects of
10 ppm, [8] and even very long range effects could be studied. [9] The main compounds have been
-diketones and ortho-hydroxy Schiff bases. In the former a clear relation between equilibrium
isotope effects and the mole fraction is seen (Fig. 1). [10] Structure determination is especially
important for compounds with biological effects in order to properly make structure function
relationships. A very useful way of analyzing isotope effects is often principal component analysis
as demonstrated for o-hydroxy Schiff bases. [11] For intramolecularly hydrogen bonded systems it
was early clear that two-bond deuterium isotope effects on chemical shifts was a good measure of
hydrogen bond strength as demonstrated in enaminones. [12]
Figure 1. Isotope effects vs. mole fraction. Taken from Ref. 10. Reproduced with permission from
Wiley.
During my sabbatical in Sydney, Australia in 1988-89 I took up structure determination by NMR
solving the structure of the sea worm toxin Neurotoxin B-IV. This was later followed by
equinatoxin, a pore forming protein (Fig. 2). A standard protein, BPTI, have been studied using both
isotope effects and 13C,H coupling constants as well as titration studies.[13],[14] An interesting twist
was the observation of fibril formation at physiological pH for the BPTI mutant 3-58 BPTI
(R42S,R53E) despite the fact that this mutant still has three disulphide bridges and fibrils are
supposed to consist of antiparallel -sheets. (See Fig. 3 ). Deuterium isotope effects on 15N chemical
shifts of the peptide nitrogens have been investigated to obtain structural information. [15] Likewise,
studies of deuterium isotope effects on 15N chemical shifts of ammonium groups of lysines have been
used to establish the presence or absence of salt bridges (Fig. 4). [16]
Figure 2. Equinatoxin.
Reproduced with permission
from J.Mol.Biol.
Figure 3. Fibrils
Figure 4. Salt bridges.
Reproduced with permission from
the American Chemical Society
Ab initio calculations were early on used to estimate deuterium isotope effects of solvated
ammonium ions to elucidate the structure and peculiarities of solvated ammonium ions . [17]
Relatively early we also investigated the optimal functionals and basis sets to be used in
intramolecularly hydrogen bonded compounds and the physical parameters such as structure, IR and
NMR parameters. [18] Using DFT functionals this kind of studies have been extended to ohydroxyacyl aromatics and establishing the relations between asymmetry of the hydrogen bond
potential, the OH bond length and the deuterium isotope effects on 13C chemical shifts. [19]
Humic acid, one of the most abundant organic compounds on earth has attracted enormous attention
both because of its ability to bind other compounds and thereby prevent or delay pesticides or PAH
to reach the ground water reservoirs and because of its complex structure. A major theme for us has
been to investigate the binding of polycyclic aromatics to humic acid attached to columns [20],
binding and degradation of a number of other important pollutants such as diuron, esfenvalerate and
glyphosate. The structural problem has been attacked using 13C NMR and spectral databases (see
Fig. 5).
Isotope effects have been used in many different context, one example is the thioamide shown in Fig.
6 in which an old idea combined with electric field effects has been revitalized in order to explain
the long range isotope effect observed e.g. at the fluorine, nine bonds away. [22] Also 8hydroxyquinoline N-oxides show very interesting isotope effects [23] as does 10hydroxybenzo[h]quinolones. [24]
Figure 5. Suggested structural elements not necessarily attached as shown.
HA is humic acid, FA is fulvic acid. Reproduced with permission from Wiley.
Figure 6.
For ten years an intensive collaboration has been going on with the Science University of
HoChiMinhCity supported by a Danida grant. This has introduced us to natural products chemistry
which is now an active part of research looking for anti-cancer compounds from weeds. Being on
University missions to China this has also opened for collaborations in China both on natural
products [25] and on energy themes. In the latter respect we are particularly interested in dye
sensitized solar cells [26], TCM and biorefineries.
Administrative positions
Over the years I have been the chairman of the Danish Society for Molecular Spectroscopy, president
of the Danish chemical society, President of Horizons in H-bond research, being in charge of an
INTAS project, organizing international summer schools on Protein NMR and isotope effects,
organizing an international conference on hydrogen bonding, been guest editor for journal of
Molecular structure, Current Organic Chemistry and Molecules. On the advisory board for the Centre
of excellence, “Centre for Photoactive Materials”, Polish Academy of Science, Warsaw.
For a full list of publications see: http://www.ruc.dk/~poulerik
1.
P. E. Hansen, O. K. Poulsen and A. Berg, 13C - 13C Coupling Constants and Substituent Effects on 13C Chemical
Shifts in 13C Labelled Pyrene and Pyrene Derivatives. Org. Magn. Reson., 7 (1975) 23-26.
2.
P. E. Hansen, 13C - 13C Long Range Coupling Constants. A Review. Org. Magn. Reson., 9 (1978) 215-233.
3. P. E. Hansen and A. Berg, 13C - 13C Coupling Constants in Dimethyl Phthalate and Phthalic Anhydride.
Determinations of signs. III. Org. Magn. Reson., 8 (1976) 591-597.
4. P. E. Hansen, A. Berg, H. J. Jacobsen, A. P. Manzara and J. Michl, 13C - 19F Spin-spin Coupling Constants in
some Monofluoro-substituted Polycyclic Aromatic Hydrocarbons. Org. Magn. Reson., 10 (1977) 179-187.
5. P. E. Hansen, J. Feeney and G. C. K. Roberts, Long-Range 13C - 1H Spin-Coupling Constants in Aminoacids.
Conformational Applications. J. Magn. Reson., 17 (1975) 249-261.
6. P. E. Hansen, Carbon-hydrogen Coupling Constants, a review. Progress NMR Spectros, 14 (1981) 175-296
7. U. Skibsted and P. E. Hansen, 1H NMR Spin-echo Spectroscopy of Erythrocytes. Transformation of
Exogenous Compounds. NMR in Biomed., 3 (1990) 248-258.
8. P. E. Hansen, F. Duus and P. Schmitt, Deuterium Isotope Effects on 13C Nuclear Shielding as a Measure of
Tautomeric Equilibria. Org. Magn. Reson., 18 (1982) 58-61.
9. P. E. Hansen, U. Skibsted and F. Duus, Long-range Deuterium Isotope Effects in Tautomeric ßThioxoketones. A 1H and 13C NMR Study. J. Phys. Org. Chem., 4 (1991) 225-232.
10. S. Bolvig and P. E. Hansen, Deuterium Isotope Effects on 13C Chemical Shifts as a Probe for Tautomerism
in Enolic ß-Diketones. Magn.Reson.Chem. 34 (1996) 467 - 478.
11. P.M. Dominiak, A. Filarowski, P.E. Hansen, K. Wozniak, Factor Analysis of 13C Isotope Effects and
13
C NMR chemical Shifts in Schiff Bases. Chem. Eur.J. 11 (2005) 4758-4766.
12. P. E. Hansen, R. Kawecki, A. Krowczynski and L. Kozerski, Deuterium Isotope Effects on 13C and 15N Nuclear
Shielding in Intramoleculary Hydrogen-bonded Compounds. II. Investigation of Enamine Derivatives.
Acta Chem. Scand., 44 (1990) 826-832.
13. P. E. Hansen, Assignment of the Natural Abundance 13C Spectrum of Proteins using 13C 1H Detected Hete
ronuclear Multiple Bond Correlation NMR Spectroscopy. Structural Information and Sterospecific Assign
ment from Two- and Three-Bond Carbon-hydrogen Coupling Constants. Biochemistry 30 (1991) 10457-66.
14. E. Tüchsen and P. E. Hansen, Resonance Assignment of the Carbonyl 13C NMR Spectrum of Basic
Pancreatic Trypsin Inhibitor by Selective Hydrogen Isotope Labelling and Isotope Effects on Nuclear Shiel
ding. Biochemistry, 27 (1988) 8568-8576.
15. J.Abildgaard, A.LiWang, M.N.Manolo and P.E.Hansen, Peptide Deuterium Isotope Effects on Backbone 15N
Chemical Shifts in Proteins. J.Biol. NMR. 44 (2009) 119-24.
16. Jennifer H. Tomlinson, Saif Ullah, Poul Erik Hansen and Mike P. Williamson. Characterisation of salt bridges to
lysines in the Protein G B1 domain. J.Am.Chem.Soc. 131 (2009) 4674-84.
17. M. Munch, Aa. E. Hansen, P. E. Hansen and T. D. Bouman, Ab-Initio Calculations of Deuterium isotope Ef
fects on hydrogen and Nitrogen nuclear Magnetic Shielding in the hydrated Ammonium Ion. Acta Chem.
Scand., 46 (1992) 1065-1071.
18. J. Abildgaard and P. E. Hansen, Quantum Mechanical Model Calculations in Chemistry: Structure,
Vibrations, Chemical Shifts and Isotope Effects on Chemical Shifts (in Polish). Wiadomosci Chemiczne 54
(2000) 846-887.
19. J. Abildgaard, S. Bolvig and P.E. Hansen, Unravelling the Electronic, Steric and Vibrational Contributions
to Deuterium Isotope Effects on 13C Chemical Shifts by ab initio Model Calculations. Intramolecular
Hydrogen bonded o-Hydroxy Acyl Aromatics. J.Am.Chem.Soc. 120 (1998) 9063-9069.
20. T. Nielsen, K. Siigur, C. Helweg, O. Jørgensen, P. E. Hansen and U.Kirso, Sorption of Polycyclic
Aromatic compounds to Humic Acid studied by Applying High Performance Liquid Chromatography.
Environm.Sci.Technol. 31 (1997) 1102-1108.
21. Christian Nyrop Albers, Poul Erik Hansen, 13C-NMR chemical shift databases as a quick tool to evaluate structural
models of humic substances. Open.Magn.Reson.J. 3 (2010) 96-105.
22. Jacek G. Sosnicki, Morten Langaard and Poul Erik Hansen, Long-range Deuterium Isotope Effecs on 13C chemical
Shifts of intramolecularly hydrogen bonded N-substituted-3-(cycloamino) thiopropionamides or amides: a case of
electric field effects. J. Org. Chem. 72 (2007) 4108-4116.
23. T. Dziembowska, A. Rozwadowski and P. E. Hansen, Intramolecular Hydrogenbonding of 8Hydroxyquinoline N-oxides, Quinaldinic Acid N-oxides and Quinaldinamide N-oxide. Deuterium Isotope
Effects on 13C Chemical Shifts. J.Mol.Struct. 436-437 (1997) 189-199.
24. Poul Erik Hansen, Fadhil S. Kamounah and Daniel T. Gryko, Deuterium isotope effects on 13C chemical shifts of
10-Hydroxybenzo[h]quinolones. Molecules, 18 (2013) 4544-4560
25. Ming Liu, Poul Erik Hansen and Xiukun Lin, Bromophenols in marine algae and their bioactivities. Marine Drugs 9
(2011) 1273-92.
26. Phuong Tuyet Nguyen, Poul Erik Hansen, Torben Lund, The effect of 4-tert-butylpyridine and Li+ on the
thermal degradation of TiO2 – bound ruthenium dye N719. Solar energy, 88 (2013) 23-30.