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Change in Conformation of a Cystine Peptide on Transition from the Crystal to Solution.

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radical reactions with the solvent[81. After irrddiation'"l
in CD3CN we found the sole product to comprise a compound
which we regard as 1,2-dimethyldiaziridinone ( 4 ) [ ' O ] on the
basis of its 'H-NMR spectrum (6=2.96ppm) and an IR band
at 1882cm-I.
Under the same conditions, the thione ( 3 b ) [readily accessible by dealkylation of ( 5 ) , CH,OSO, instead of BF,["I,
with triethylamine in acetonitrile] is quantitatively converted
into sulfur and dimethylcarbodiimide ( 6 ) , which was identified
by its 'H-NMR and IR spectrum['21 and by hydrolysis to
N,N'-dimethylurea. This reaction possibly proceeds cia the same
intermediate as was recently trapped by 3 2 cycloaddition
during the thermolysis of 5-imin0-1,2,3,4-thiatriazolines['~~.
+
Preparation of the very hygroscopic imine ( 3 c ) in two
steps from ( 5 ) is an example of a new synthesis, which readily
permits variation of the substituent attached to the imino
nitrogen atom of 2-tetrazolin-5-imines. Photoly~is[~'
of (3c)
in D,-THF affords 14-17 % of (6) and 83-86
of diaziridinimine (7) which is identical with an authentic sample['41.
The methyl azide expected to accompany (6) apparently
decomposes under the reaction conditions.
(3dj, R' = RZ = CH3; (9d).
( 3 e ) , R' = H, R2 = C(CH,),;
~ 1 =%9 0
: 10
(9e), E l % = 9 4 : 6
O n treatment of (8) with sodium hydride in tetrahydrofuran
we obtained the methylenetetrazolines (3d) and ( 3 e ) as intensely yellow, extremely air- and moisture-sensitive distillable
oils. Their p h o t ~ l y s i s [at
~ ] -60°C in D,-THF (Pyrex filter)
quantitatively afforded the aziridinimines ( 9 ) . whose structure
and configuration were confirmed by spectral comparison
with authentic compounds['51.The E/Z isomer ratio remained
unchanged for weeks at -20°C. The high stereoselectivity
of this photolysis is remarkable. Methylenediaziridines could
not be detected.
Received: February 12. 1975:
in shortened form: March 14, 1975 [Z 207 IE]
German version: Angew. Chem. 87.422 (1975)
CAS Registry numbers:
13a). 13576-20-0; ( 3 b ) . 54986-14-0: / 3 c ) , 35151-69-0:
13dt. 54986-15-1 ; (3e). 54986-16-2; ( 4 ) . 54986-17-3: ( 5 ) . 54986-19-5:
(6). 4852-30-6: (71, 54986-20-8: ( 8 ) . R' =R'=CH,, 54986-22-0.
( 8 ) . R i = H , R'=C(CH,),, 54986-24-2; Z - ( 9 d ) . 54986-25-3:
E- f Yd). 54986-26-4 : Z - ( 9 e ) , 27270-90-2 ; E - ( 9 e ) , 27270-91-9
[I] a ) P. Dowd. Accounts Chem. Res. 5 , 242 (1972); b) J. J. Gqjewski. A .
Yeshurun. and E . J . Bair. J. Amer. Chem. Soc. 94. 2138 (1972): J. A . Burson. L. R . Corwin, and J . H . Dacis. ibid. 96, 6177 (1974).
Arigew.
Chem. inrcvnur. Edir. / Vul. 14 ( 1 9 7 5 ) / N o . 6
[2] J. F . Liehriian and A . Greeriberg. J. Org. Chem. 3Y. 123 (1974). and
references cited therein: M . E . Zaridler, C. E. Choc. and C. K. Jo/iri,sorr.
J. Amer. Chem. SOC. 96. 3317 (1974). and references cited therein:
B. K. Carpenter, J. C. S. Perkin 11 1974. I .
[3] W-D. Stohrer, P. Jacob\, K . H . Kaiser. G . Wirch. and G. Quiriherr.
Fortschr. Chem. Forsch. 46, 181 (1974): S . D. Andrews and A. C. Day.
J. Chem. SOC. B 1968, 1271: R. J. Cruwford. D. M . Car?ieron, and
H . Tokunasa. Can. J. Chem. 52. 4025 (1974).
[4] H. H . Wassrrman, G . M. Clark, and P. C . Tur1ry. Fortschr. Chem.
Forsch. 47. 73 (1974). and references cited therein: K. G. Sriniuasan
and J . H . B o w r . J. C. S. Chem. Comm. 1974. 379
J . A . Schuryser and F . C . De Srhrywr, Chem. Ind. (London) IY72.
165.
P. S . Erryel and L . Slieri. Can. J. Chem 52. 4040 11974).
Photolysis of 1.4.5-trisubstituted 2-tetrazolines: T Aki?.nriiii. T Kiriiiviuru. T lsidu. and M . Kawrii.\i. Chem. Lett. IY74. 1x5.
W S . Widsivorth. Jr.. J . Org. Chem. 34. 2994 (1969).
All photolyses conducted in sealed NMR sample tubes. previouhly
repeatedly degassed at l o - ' torr, with a 150 or 450 W Hg lamp.
Only 1.2-di-rerr-alkyl-substituteddiaziridinones are so far known : F .
D. Grernr, J . C . S t o w / / . and W R. Bergmark. J. Org. Chem. 34, 2254
( 1969).
S . Huniy and K . H . Oette, Liebigs Ann. Chem. 641, 94 (1961).
G . Papi and G. Shruna. J. Amer. Chem. Soc. 93, 5213 (1971).
E. can Loork, J . - M . Vandensaael. C. L'Ahhe, and G. Snirts. J. Org.
Chem. 38, 2916 (1973): R. Neidlein and K. Sakmann. Synthesis 1975.
52: M . Recirt, J. C. S. Chem. Comm. 1975, 24.
K.-H. Ross, Dissertation, Universitat Wurzburg 1974.
( I O d ) : H. Quasr and P. SchPfer. unpublished. f l o e ) ' H . Quast and
E . Schmirr, Angew. Chem. 82. 395 (1970). Angew. Chem. internat. Edit.
9, 381 (1970). '
Change in Conformation of a Cystine Peptide on Transition from the Crystal to Solution
By Giinther Jung, Michael Ottnad, Peter Hartter, and Heinrich
Lachrnann"]
Dedicated to Professor Eugen Miiller on the occasion of his
70th birthday
During investigations on the chiroptical behavior of the
disulfide chromophore in peptides['l an initially surprising
effect was observed. On repetitive recording of the C D spectrum of tert-butyloxycarbonyl-L-cysteinylglycylcysteinedisulfide methyl ester ( 1 ) a hypsochromic shift of the longest
wavelength negative Cotton effect and a simultaneous increase
in ellipticity were registered; in addition, hypsochromism of
the disulfide Cotton effect at 245nm and hyperchromism of
the Cotton effect at 225nm (Fig. l a ) also occurred. Since
chemical reactions can be ruled out, it appears likely that
the time-dependent changes are related to a conformational
transition on going from the crystal to the solution. During
such a process a twisting of the disulfide group and E/Z
isomerization of the two peptide bonds in the heterodetic
ring and the urethane bond can occur simultaneously or consecutively. In order to establish whether the time-dependent
change of the C D and UV absorption (Fig. 1 b) is due to
only one or to several of these processes we undertook a
kinetic-spectroscopic analysis[2!
Merely the appearance of an isosbestic point in the UV
spectra and of two analogous points of constant ellipticity
in the C D spectra suggest that the overall conformational
change proceeds in a spectroscopically uniform manner. This
can be tested with the aid ofextinction (E)diagrams,extinction
[*I
Prof. Dr. G. Jung [ + ] and Dr. M. Ottnad
Chemisches Institut der Universitit
74 Tubingen I , Auf der Morgenstelle (Germany)
Dr. P. Hartter
Physiologisch-chemisches Institut der Universitit Tubingen
Dr. H. Lachmann
Physikalisch-chemisches lnstitut der Universitlt Tubingen
[ +] T o whom correspondence should be addressed.
429
Or
-t
E
I
6o
40
5
-
E
20
I
c
._
E
g -40
3.- 0
._
-,-
30
.-0
60
100
3
2m -60
'=p -20
E -10
.-
2 -80
c
2 -60
L
g -80
-100
._
n
220
240
260
280
X [nrnl-
320
300
3LO
0
07
120
I
Boc-L-Cys-Gly-Cys-OMe
I P 267.5
80
0.1
&
220
240
260
280
300
320
3LO
100
360
li [nmlFig. 1. a) Time-dependence of the C D spectra of (I) in 95 %ethanol. c z
mol/l; 20°C; d=20mm (h>260nm), d = 2 m m (ht260nm); t , = 5 , 30, 60,
100, 150, 230min after dissolution of ( I ) . b) Time-dependence of the UV
spectra of ( 1 ) in 95% ethanol. C S I O - ~ mol/l; 20°C; d = 2 0 m m , t , = 5 , 15,
35, 70,120. 240,500 min after dissolution of ( I ) .
difference (ED) diagramsf2](Fig. 2), and ellipticity diagrams
(Fig. 3). Plotting of extinction values &(ti) taken from the timedependent UV spectra (Fig. 1 b) at a particular wavelength
uersus the analogous &(ti) values taken at another wavelength
yields an E diagram. For small changes, but very different
absolute values, of &(ti) (as in Fig. 1b) it is better to calculate
the differences A f Z x = E ~ ( t i ) - E ~ ( t in
l ) each case and to plot
them against one another ( E D diagrams, Fig. 2).
If [el values or dichroic amplitudes are taken from the
time-dependent CD spectra (Fig. 1 a) and plotted against each
other in analogous manner then ellipticity diagrams'' are
obtained (Fig. 3). In the case of spectroscopically uniform
reactions all these diagrams should afford straight lines for
any combination of wavelengths; this requirement is well
satisfied in the present case.
AEk-
-010
-0.06
-100
-60
-80
-40
-20
0
20
Dichroic amplitude [mml
1
lj
-100
360
co
O
I
t -20
-
40
1
158
60
Fig. 3. Ellipticity diagrams: dichroic amplitudes at 275 nm taken from
Fig. 1a and plotted against the corresponding values at eight other wavelengths
(nonlinear time scale as auxiliary axis).
dissymmetric CSSC grouping or with strict mechanical coupling to this twisting (linear dependence), then the conformational change occurring on transition from the crystal to
solution takes place in a spectroscopically uniform manner.
Thus the assumption is confirmed that twisting of the disulfide
group-accompanied by conformational changes of the entire
heterodetic ring-occurs in ( I ) on transition from the crystal
to solution. The possible E / Z isomerization of the urethane
bond does not appear to be incorporated in the observed
temperature dependence of the CD and UV spectra of (I).
Many of the spectroscopic data for peptides and other
nonrigid molecules which were previously considered to be
independent of time should be subjected to critical scrutiny.
The relevance of these phenomena, which we have already
observed for various other examples, to the interpretation
of X-ray structure analyses and of structure-activity relations
is obvious.
Received: March 6, 1975 [Z 208 IE]
German version: Angew. Chem. 87, 448 (1975)
CAS Registry numbers:
( 1 ) . 52071-43-9
[1] a) G. Jung and M. Ottnad, Angew. Chem. 86, 856 (1974); Angew. Chem.
internat. Edit. 13, 818 (1974); b) M. Ormad, C. Ortnad. P. Hartfer, and
G.Jun~/.Tetrahedron,31,1155(1975);c)M.Ortnad.
P. Harrrer.and G.Juny.
Hoppe-Seyler's Z. Physiol. Chem., in press, and references cited therein.
[2] a) H. Mauser, 2. Naturforsch. 23b, 1021, 1025 (1968); b) H. Lachmann,
H. Mauser, F . Schneider, and H . Wenck, ibid. 26b, 629 (1971); c) H.
Lachmann, Dissertation, Universitat Tubingen 1973: d) H. Mauser: Formale Kinetik. Bertelsmann-Universitiits-Verlag. Dusseldorf 1974: e) H .
Lachmann, to he published.
Formation of Radical Cations from 1,2- and 1 , 4
Dimethoxybenzene by Electron Transfer to TI * and
Ag2+ in Aqueous Solution.
A Pulse Radiolysis and in situ Radiolysis EPR Study
+
-0 02
By Prrer O'Neill, Steen Stc~cnkon.and
Dietrich Schulte-Frohlindri'l
Fig. 2. Extinction difference diagrams: the values are taken from automatically
repeated UV spectra (recordingconditions as for Fig. 1 b, except ford = 50 m m :
nonlinear time scale as auxiliary axis).
In a previous publication"' it was shown that T1° reacts
with 1,4-dicyanobenzene and 1,4-dinitrobenzene, even in
strongly acidic solution, by transfer of an electron to produce
radical anions and T1'. We now report electron transfer
from 1,2- and 1,4-dirnethoxybenzene (I) and (2), respectively,
to TI'' and Agz+ to yield radical cations and T1' and Ag'.
[*I
Consideration of models of (I) show that mutually independent isomerizations of the disulfide group and the intraannular
peptide bonds are impossible. If all processes within the heterodetic ring occur synchronously with twisting of ihc inherently
430
Dr. P. ONeill, Dr. S. Steenken, and
Prof. Dr. D. Schulte-Frohlinde [ +]
Institut fur Strahlenchemie im Max-Planck-Institut
fur Kohlenforschung
433 Mulheim/Ruhr, Stiftstrasse 34-36 (Germany)
[+] To whom correspondence should be addressed
Angew. Chrm. internat. Edit. 1 Vol. 14 ( 1 9 7 5 )
No. 6
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