Research Overview
Yoko Sugawara
The author’s research field is biophysics by means of vibrational spectroscopy and crystallography. The author
joins the muon group since 2011 and is working to establish SR experiments as a new biophysical method.
1. Pre-resonance Raman spectroscopy and ab initio calculations of
intramolecular force fields of amide compounds (1975 ~ 1984).
The author had started research in the field of vibrational spectroscopy.
The first theme was pre-resonance Raman spectra of amide compounds. It
was shown that Raman intensities of the amide bonds such as amid I, II
and III were specifically enhanced when ultraviolet lasers were used (Fig.
1). The amide bands which reflect the second-order structure of proteinswould be selectively measured in pre-resonance/resonance Raman spectraof proteins.
Ab initio calculations of force fields of amide compounds were
examined and it was revealed that the calculations offer valuable
information on the off-diagonal elements of the force fields which were

Fig. 1 Raman spectra ofpoly(L-glutamic acid) in D2O
exited by the 488.0 (a) and
257.3 nm (b) lase lines

often difficult to be determined only by the empirical method.
2. Crystallographic analysis of temperature and/or humidity induced phase transitions among pseudopolymorphsof nucleotides (1982 ~)Humidity- and temperatur-induced structural transitions occur in the cases of many hydrate crystals. Lossof water molecules in crystals lower the crystallinity in general. However, single crystal–single crystal
transitions were found to proceed in the case of nucleotide or nucleoside hydrates due to flexibility of thestructure, e.g., conformational changes and reconstruction of hydrogen bonding networks (Fig.2).
The transitions usually accompany large hysteresis, and metastable states easily appear. There were
peculiar transitions in which the intermediate phase observed in the absorption was different from that observedin the desorption processe (a cyclic transition), andtwo different dehydrated crystal structures appeared
depending on the temperature conditions (a bifurcate
transition) (Fig. 3). These characteristics cause
attention from a view point of physical properties.
Recently, we revealed the mechanism of the transitionon the basis of the crystal structures of theintermediate phases where the double or the triple
periodic structure appeared. The analysis was carriedout by not only X-ray crystallographic method but
also neutron diffraction, Raman spectroscopy andmolecular dynamics calculations to reveal theFig. 2 Humidity induced phase transition of disodium
adenosine 5’-triphsphate. Crystal structures of thedehydrate (a) and the trihydrate (b)Blue circle, water molecules lost in the dihydrate; orange
circle, moiety where conformational changes were
induced.

mechanism of phase transitions.
Similar phenomenon occurs in protein crystals.
Decrease of water contents induces single crystal-single
crystal transitions in the cases of xylose isomerase,
thaumatin etc.. Crystal structure analysis and theoretical
calculation to evaluate interactions have been carried out
paying attention to a role of solvents in crystal formation.
3. SR studies of biomacromolecules (2011~)

At the start of Grant-in-Aid for Scientific Researchon Innovative Areas “Frontier of Materials, Life andFig. 3 Three types of phase transitions of
nucleoside/nucleotide hydrates
Red and blue arrows indicate desorption andabsorption process, respectively.

Elementary Particles Science explored by Ultra Slow
Muon Microscope”, the author joined the group to apply SR to biophysical research. The research isconnected with the proposal at Toyota Physical and Chemical Research Institute as a visiting fellow.
The muon () is an elementary particle with a positive or a negative electric charge (e) and a spin of
1/2. When a positively charged muon (+) is implanted into materials, it captures an electron and amuonium (Mu) which is a hydrogen-like exotic atom is formed. It attacks an unsaturated bond ofcompounds and a radical, conventionally called as a muonium radical, is formed. The spin states of a muonor a muonium reflect the local magnetic field around the stopping sites and are monitored through thedirection of a positron which is emitted when the muon or the muonium decays with a mean lifetime of
2.2 s (Fig. 4).
Nagamine and his collaborators applied SR to monitor electron transfer process in cytochrome cwhich is a member of a respiratory chain in mitochondria. They used "the labelled electron method"developed in the research of electron movement along trans-polyacethylene (Nagamnieet al., Phys. Rev.
Lett. 53 (1984)1763.). The values of the relaxation parameter were found to depend on water contents andtemperature. The information on muon stopping sites in proteins is inevitable to deepen understanding of
the results. Experimental and theoretical approach to determine muon stopping sites on the basis of SRdata of basic components of biomacromolecules is in progress (Fig. 5).

Fig. 4

Schematic diagram of the SR experimentFig. 5 SR spectra of glycine (a) and N-methylacetamide (b)Muon (+) and muonium (Mu) radical are the main
components, respectively.

Publication List
(Original papers)

1.

Harada, Y. Sugawara, H. Matsuura and T. Shimanouchi,"Preresonance Raman spectra ofsimple amides using ultraviolet laser" J. Raman Spectrosc. 4, 91-98(1975).

2.

Y. Sugawara, H. Hamaguchi, I. Harada and T. Shimanouchi, "Resonance Raman spectra of Nmethylthioacetamide" Chem. Phys. Lett. 52, 323-326(1977).

3.

Y. Sugawara, I. Harada, H. Matsuura and T. Shimanouchi, "Preresonance Raman studies ofpoly(L-lysine), poly(L-glutamic acid), and deuterated N-methylacetamides" Biopolymers, 17,1405-1421(1978).

4.

Y. Sugawara, Y. Hamada, A. Y. Hirakawa and M. Tsuboi, "Occurrence of the cis-peptide ingaseous N-methylformamide as revealed by rotational structure in its infrared
spectrum"Chem. Phys. Lett. 67, 186-188(1979).

5.

Y. Sugawara, Y. Hamada, A. Y. Hirakawa, M. Tsuboi, S. Kato and K. Morokuma, "Ab initio MO
calculation of force constants and dipole derivatives for formamides" Chem. Phys. 50, 105111(1980).

6.

Y. Sugawara, A. Y. Hirakawa, M. Tsuboi, S. Kato and K. Morokuma, "Force constants of transand cis N-methylformamide from ab initio SCF MO calculations" Chem. Phys. 62, 339351(1981).

7.

K. Ichikawa Y. Hamada, Y. Sugawara, M. Tsuboi, S. Kato and K. Morokuma, "Ab initio study
on cyanamide and isocyanamide" Chem. Phys. 72, 301-312(1982).

8.

Y. Hamada, N. Tanaka, Y. Sugawara, A. Y. Hirakawa, M. Tsuboi, S. Kato and K.
Morokuma"Force field in the methylamine molecule from ab initio MO calculation" J. Mol.
Spectrosc. 96, 313-330 (1982).

9.

Y. Sugawara, Y. Hamada and M. Tsuboi, "Vibration-rotation spectra of formamides" Bull.
Chem. Soc. Jpn. 56, 1045-1050(1983).

10. N. Tanaka, Y. Hamada, Y. Sugawara, M. Tsuboi, S. Kato and K. Morokuma, "Force field in thehydrazine molecule from ab initio MO calculation" J. Mol. Spectrosc. 99, 245-262(1983).
11. Y. Sugawara, M. Iwamori, J. Portoukalian and Y. Nagai, "Determination of Nacetylneuraminic acid by gas chromatography-mass spectrometry with a stable isotope asinternal standard" Anal. Biochem. 132, 147-151(1983).
12. Y. Sugawara and H. Iwasaki, "Structure of disodium uridine diphosphoglucose dihydrate andrefinement of dipotassium glucose 1-phosphate dihydrate (monoclinic form)" Acta Crystallogr.
C40, 389-393(1984).
13. Y. Sugawara, A. Y. Hirakawa and M. Tsuboi, "In-plane force constants of the peptide group:
Least-squares adjustment starting from ab initio values of N-methyacetamide" J. Mol.
Spectrosc. 108, 206-214(1984).
14. S. Matsuura, T. Sugimoto, S. Murata, Y. Sugawara and H. Iwasaki, "Stereochemistry of
biopterin cofactor and facile methods for the determination of the stereochemistry of abiologically active 5,6,7,8-tetrahydropterin" J. Biochem. 98, 1341-1348(1985).
15. T. Sugawara, S. Murata, K. Kimura, H. Iwamura, Y. Sugawara, and H. Iwasaki, "Design ofmolecular assembly of diphenylcarbenes having ferromagnetic intermolecular interactions, "J.
Am. Chem. Soc. 107, 5293-5294(1985).
16. Y. Sugawara, H. Iwasaki, N. Suzuki,and S. Okuda, "Structure of 2-acetamido-3-amino-2,3dideoxy-D-glucofuranurono-6,3-lactam"Carbohydr. Res. 142, 195-201(1985).
17. Y. Sugawara, A. Y. Hirakawa, M. Tsuboi, S. Kato, and K. Morokuma, "Ab initio SCF MO study
on the force field of amides" J. Mol. Spectrosc. 115, 21-33(1986).
18. H. Urabe, Y. Sugawara, M. Tsukakoshi, A. Ikegami, H. Iwasaki, and T. Kasuya, "Raman
spectroscopic study on low-frequency collective modes in self-associates of guanosine
monophosphates" Biopolymers, 26, 963-971(1987).
19. Y. Wakatsuki, H. Yamazaki, T. Kobayashi and Y. Sugawara, "Effect of electron-withdrawing
substituents on the cobalt(I)-coordinated cyclopentadienyl ring. Spectra and diene substitution
kinetics of [Co(C5H4X)(1,5-cyclooctadiene)]" Organometallics, 6, 1191-1196(1987).
20. T. Nozaka, I. Morimoto, M. Ishino, T. Okitsu, H. Kondoh, K. Kyogoku, Y. Sugawara and H.
Iwasaki, "Mutagenic principles in Sinomeni Caulis et Rhizoma. I. The structure of amutagenic alkaloid, N-demethyl-N-formyldehydronuciferine, in the neutral fraction of themethanol extract" Chem. Pharm. Bull. 35, 2844-2848(1987).
21. H. Ohta, K. Nagasaka, H. Takeuchi, I. Harada, Y. Sugawara and H. Iwasaki, "Latticedynamical calculations of N-methyl-N-ethyl-morpholinium bis(tetracyanoquinodimethane)
above and below the spin-Peierls transition temperature" Phys. Rev. B, 37, 7691-7697(1988).
22. K. Umemoto, S. Oikawa, M. Aida and Y. Sugawara, "Intermolecular nuclear Overhauser effectand atomic pair potential approaches to wheat germ agglutinin-sugar binding" J. Biomol.
Struc. Dynam. 6, 593-608(1988).
23. M. Tokumoto, K. Murata, N. Kinoshita, K. Yamaji, H. Anzai, Y. Tanaka, Y. Hayakawa, K.
Nagasaka and Y. Sugawara, "Superconductivity in BEDT-TTF based organic metals: Role ofuniaxial pressure and inverse isotope effect" Mol. Cryst. Liq. Cryst. 181, 295-304(1990).
24. Y. Tanaka, N. Kinoshita, Y. Asai, M. Tokumoto, Y. Hayakawa, K. Nagasaka and Y. Sugawara,"Isotope effect in TTF-analog based organic superconductors" Synthetic Metals, 42, 22312234(1991).
25. Y. Sugawara, N. Kamiya, H. Iwasaki, T. Ito and Y. Satow, "Humidity-controlled reversible
structure transition of disodium adenosine 5'-triphosphate between dihydrate and trihydrate
in a single crystal state" J. Am. Chem. Soc. 113, 5440-5445(1991).
26. H. Urabe, Y. Sugawara, M. Tsukakoshi, and T. Kasuya, "Low-frequency Raman spectra of
guanosine and nucleotides in ordered state: origin of the lowest-frequency mode" J. Chem.
Phys. 95, 5519-5523(1991).
27. T. Tachikawa, A. Izuoka, R. Kumai, T. Sugawara, and Y. Sugawara, "Preparation andproperties of double-bridged BEDT-TTF dimer and its perchlorate salt" Solid State Comm. 82,
19-22(1992).
28. T. Mochida, S. Matsumiya, A. Izuoka, N. Sato, T. Sugawara and Y. Sugawara, "Structure of 3hydroxyphenalenone" Acta Crystallogr. C48, 680-683(1992).
29. T. Sugawara, T. Mochida, A. Miyazaki, A. Izuoka, N. Sato, Y. Sugawara, K. Deguchi, Y.

Moritomo, and Y. Tokura, "Organic paraelectrics resulting from tautomerization coupled with
proton-transfer" Solid State Comm. 83, 665-668(1992).
30. H. Iwasaki, Y. Sugawara, T. Adachi, S. Morimoto and Y. Watanabe, "Structure of 6-Omethylerythromycin A (clarithromycin) " Acta Crystallogr. C49, 1227-1230(1993).
31. Y. Tanaka, M. Tokumoto, and Y. Sugawara, "Isotope effect and intramolecular vibration on
C60" Trans. Mat. Res. Soc. Jpn. 16A, 345-348(1994).
32. Y. Sugawara, Y. Iimura, H. Iwasaki, H. Urabe and H. Saito, "Reversible crystal transition of
guanosine between the dihydrate and anhydrous state coupled with adsorption-desorption
process" J. Biomol. Struct. Dyn. 11, 721-729(1994).
33. H. Urabe, Y. Sugawara and T. Kasuya,"Humidity-dependent structural transition of guanosine
and Na2ATP crystals studied by low frequency Raman spectroscopy" Phys. Rev. B51, 56665672(1995).
34. Y. Tanaka, M. Tokumoto and Y. Sugawara, "Isotope Effect on Intramolecular Vibration of C60"
Fullerene Sci. & Tech. 3, 179-223(1995).
35. Y. Sugawara, "Phase transition of nucleotides induced by relative humidity" Proc. The 24th
Seminar on Science and Technology Crystallography, 91-98(1995).
36. M. Aida, Y. Sugawara, S. Oikawa and K. Umemoto, "Structural fluctuation of methyl N,N'diacethyl-β-D-chitobioside in vavuo and in aqueous solution: molecular dynamics simulations
and protone NMR spectroscopy" Int. J. Biol. Macromol. 17, 227-235(1995).
37. Y. Yokoyama, S. Uchida, Y. Yokoyama, Y. Sugawara and Y. Kurita "Diastereoselective
photochromism of an (R)-binaphthol-condensed indolylfulgide"J. Am. Chem. Soc. 118, 31003107(1996).
38. Y. Sugawara, H. Urabe, K. Kobayashi, Y. Iimura and H. Iwasaki, "Crystal structure andhumidity-induced phase transition of disodium salt of adenosine 5'-monophosphate" Mol.
Cryst. Liq. Cryst. 227, 255-258(1996).
39. G. Ono, A. Izuoka, T. Sugawara and Y. Sugawara, "Unusual conductive behavior of (BEDTTTF)3Cl2 hydrate salts" Mol. Cryst. Liq. Cryst. 285, 63-68 (1996).
40. T. Okuno, A. Izuoka, T. Ito, S. Kubo, T. Sugawara, N. Sato, and Y. Sugawara, "Reactivity ofmesogenic diacetylenes coupled with phase transitions between crystal and liquid crystal
phases" J. Chem. Soc., Perkin Trans. 2, 889-895(1998).
41. H. Urabe, Y. Sugawara, M. Ataka and A. Rupprecht, "Low-frequency Raman spectra oflysozyme crystals and oriented DNA films: Dynamics of crystal water" Biophys. J. 74, 15331540(1998).
42. S. Yamamura, M. Takata, M. Sakata and Y. Sugawara, "Nature of the hydrogen bond in
tetragonal KDP(KH2PO4) observed by maximum entropy method" J. Phys. Soc. Jpn. 67, 41244127(1998).
43. G. Ono, A. Izuoka, T. Sugawara and Y. Sugawara, "Structure and physical properties of ahydrogen-bonded self-assembled material composed of a carbamoylmethyl substituted TTF
derivative" J. Mater. Chem. 8, 1703-1709(1998).
44. S. Yamamura, Y. Sugawara, M. Takata and M. Sakata, "Imaging of the electron density

distributions of hydrogen in LiH and LiOH by maximum entropy method "J. Phys. Chem.
Solids, 60, 1721-1724(1999).
45. Y. Sugawara, A. Nakamura, Y. Iimura, K. Kobayashi and H. Urabe, "Crystallographic
investigation of humidity-induced phase transition of disodium cytidine 5'-monophosphate andcrystal structure of three hydrates" J. Phys. Chem. B 106, 10363-10368(2002).
46. Y. Shindo, A. Naito, S. Tuzi, Y. Sugawara, H. Urabe and H. Saito, "Stepwise conformationaltransition of crystalline disodium adenosine 5'-triphosphate with relative humidity as studied
by high resolution solid state 13C and 31P NMR" J. Mol. Struct. 602-603, 389-397(2002).
47. M. Fujihashi, D. H. Peapus, E. Nakajima, T. Yamada, J. Saito, A. Kita, Y. Higuchi, Y.
Sugawara, A. Ando, N. Kamiya, Y. Nagata and K. Miki, "X-ray crystallographic
characterization and phasing of a fucose-specific lectin form Aleuria aurantia" Acta
Crystallogr. D59, 378-380(2003).
48. K. Kamiya, Y. Sugawara and H. Umeyama, "Algorithm for normal mode analysis with generalinternal coordinate" J. Comp. Chem. 24, 826-841(2003).
49. S. Yoneda, Y. Sugawara and H. Urabe, "Crystal water dynamics of guanosine dihydrate:
Analysis of atomic displacement parameters, time profile of hydrogen-bonding probability andtranslocation of water by MD simulation" J. Phys. Chem. B, 109, 1304-1312(2005).
50. C. Kimura, M. Nukina, K. Igarashi and Y. Sugawara, " Hydrokyergothionein, a new
ergothioneine derivative from the mushroom Lyophyllum connatum, and its protective activity
against carbon tetrachloride-induced injury in a primary culture hepatocytes" Biosci.
Biotechnol. Biochem. 69, 357-363(2005).
51. M. Ishimaru, T. Toyota, K. Takakura, T. Sugawara and Y. Sugawara, "Helicalaggregate of oleic
acid and its dynamics in water at pH 8" Chem. Lett. 34, 46-47(2005).
52. S. Yamamura, Y. Sugawara, H. Terao，M. M. Matsushita and T. Sugawara, "Dielectric
properties associated with structural phase transitions observed in tetramethylammonium
salt of o-phenylenebis(squaric acid)" Chem Phys, 322, 392-398(2006).
53. Tohara, Y. Sugawara and M. Sato, "Preparation and characterization of meso-tetrakis(2,6diaryloxyphenyl)porphyrins" J. Porphyrins Phthalocyanines, 10, 101-116(2006).
54. S. Yoneda , Y. Sugawara and H. Urabe, "Analysis of low-frequency phonons in guanosine
dihydrate based on molecular dynamics simulations" J. Phys. Chem. A 112, 7055-7063(2008).
55. M. Ootaki, S. Endo, Y. Sugawara and T. Takahashi "Crystal habits of cubic insulin from
porcine pancreas and evaluation of intermolecular interactions by macrobond and EET
analyses" J. Crystal Growth, 311, 4226-4234 (2009).
56. H. Komatsu, M. M. Matsushita, S. Yamamura, Y. Sugawara, K. Suzuki and T. Sugawara"Influence of magnetic field upon the conductance of a unicomponent crystal of atetrathiafulvalene-based nitronyl nitroxide" J. Am. Chem. Soc. 132, 4528-4529(2010).
57. H. Takusagawa, S. Yamamura, S. Endo, Y. Sugawara, T. Inagaki and M. Nakasako, "Newmonoclinic form of bovine pancreatic ribonuclease A from a salt solution and comparison ofintermolecular interactions in ribonucleases" J. Crystal Growth, 319, 49-56(2011).
58. T. Kiyotani, and Y. Sugawara, "L-Leucylglycine 0.67-hydrate and [(4S)-2,2-dimethyl-4-(2-methylpropyl)-5- oxoimidazolidin-3-ium-1-yl]acetate" Acta Crystallogr. C68, o498-o501(2012).
59. M. Ootaki, Y. Nawa, T. Hiroi, H. Matsui and Y. Sugawara, "L-Leucylglycylglycine" Acta
Crystallogr. E69, o660(2013).
60. Y. Mizukawa, K. Suzuki, S. Yamamura, Y. Sugawara, T. Sugawara and M. Iwasaka, “Magnetic
Manipulation of Nucleic Acid Base Microcrystals for DNA Sensing” IEEE Transactions
Magnetics., 50, 500190 (2014).
61. Y. Takeuchi1, Y. Sugawara, T. Sugawara and M. Iwasaka, “Magnetic Rotation of Monosodium
Urate and Urinary Tract Stones for Clinical Treatment Applications” IEEE Transactions
Magnetics., 50, 610120 (2014).
62. Y. Sugawara, A. D. Pant, W. Higemoto, K. Shimomura, E. Torikai and K. Nagamine,"Hydration Effects on Electron Transfer in Biological Systems Studied by SR", JPS
Conference Proceedings 2, 10310-1-5(2014).
63. A. D. Pant, Y. Sugawara, I. Yanagihara, G. P. Khanal, I. Shiraki, W. Higemoto, K. Shimomura,
K. Ishida, F. L. Pratt, E. Torikai, K. Nagamine, “Hydration Effect on Electron Transfer in
Cytochrome c Monitored by μSR” JPS Conference Proceedings 8, 033007-1-5(2015).
64. Y Sugawara, Y. Hirano, S. Yamamura, S. Endo, M. Ootaki, N. Matsumoto and T. Takahashi,"Electrostatic energy of transfer and macrobond analyses of intermolecular interactions andhydration effects in protein crystals in a low ionic environment", J. Crystal. Growth, 468, 283289(2017).
65. A. D. Pant, Y. Sugawara, H. Nakanishi, E. Torikai,W. Higemoto, K. Shimomura and K.
Nagamine, “Theoretical Calculations of Charge States and Stopping Sites of Muons in Glycine
and Triglycine” JPS Conf. Proc., 21, 011038 (2018).
66. M. Tsubonoya, A. Murofushi, S. Yamamura and Y. Sugawara, “Crystal structure andsequential dehydration transitions of disodium guanosine 5’-monophosphate tetrahydrate”
Acta Crystallogr. C74, 1153-1159(2018).
67. Y. Sugawara, “Opportunities for Life Science by Use of Muon Spin Spectroscopy: With a View
to Monitoring Protein Functions” JPS Conf. Proc. 25, 011008 (2019).
(Book chapter)
1．Y. Sugawara, “Characteristics of Crystal transitions among psudopolymorphs.” Advances inorganic Crystal Chemistry, Eds. R. Tamura & M. Miyata, pp.317-334, Springer Japan, Tokyo(2015).