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The optical rotatory dispersion of purine nucleosides
BIOCHEMICAL
Vol. 22, No. 5, 1966
AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Dispersion of Purine Nucleosides'
B
T.R. Emerson, R.J. Swan and T.L.V. Ulbricht Xestfield
College, London, England and
Twyford Laboratories,
London, Englend
ReceivedJanuary 25, 1966 we have previously
reported that the Optical Rotatory Dispersion
(ORD) curves of a-purine nucleosides give positive the p-anomers give negative Cotton effects purine ~y-nucleosides 1964).
(Ulbricht
obey Hudson's Isorotation
Recently we presented preliminary
nucleosides, indicating
Cotton effects,
whereas
et al, 1964);
hence
Rules (Emerson and Ulbricht,
results
on a series of pyrimidine
that the sign and magnitude of the long wave-length
Cotton effects produced by these compoundscould be related to their conformation (Ulbricht
et al, 1965).
Further studies have confirmed these
conclusions and have madeit possible to propose a rule for predicting
the
sign of the Cotton effect
et al,
1966).
in pyrimidine
Wehave now examined fifty
results with E9-glycosides, nucleosides.
purine nucleosides, and report here our
including
cvclo-nucleosides
is excluded.
In many cases, complete ORDcurves are more difficult
purine nucleosides absorb intensely the use of very dilute
* Optical Rotatory Part IV: T.L.V. ai Dress.
aromatic
groups, which can influence the sign of the Cotton
to obtain with purine than with pyrimidine nucleosides.
necessitating
and azapurine
Consideration of compoundscontaining additional
systems (e.g. p-toluoyl Effect)
fursnose nucleosides (Ulbricht
in the ultra-violet
This is because (high e values),
solutions in the region near-h max.'
Dispersion of Nucleic Acid Derivatives, part V. Ulbricht, R.J. Swan& A.&i. Wchelson, Chem. Commun.,
505
BIOCHEMICAL
Vol. 22, No. 5, 1966
and because is
they
noticeably
purines
have
lower
following
the &g~
1) the anomeric
(N3,5'-cycloadenosine
one nucleoside
in which
the Cotton
relation
sign
of the
(D- or L-)
at the anomeric
carbon
The sign isopropylidene group
not
groups
position
in
the purine
8 in the heterocyclic effects
like
of adenosine
nucleosides
- suggesting,
has no major
between xylose
derivatives
(Ulbricht
effect et al,
If chromophore
1965;
Emerson
such ORD results with
by substitution
nucleus
(+azapurine
reference
the
stereochemistry
of acetyl
or of the 2'-OH of the
of N for
CH at
nucleosides
purinea).
give
The tri-O-acetyl
give
similar
curves
the pyrimidines,
that
to the parent
hydrogen-bonding
effect. effect
sugars,
considerably
this
as in P-L-compounds.
nor
In pyrimidine is
, since
by the nature
is
but no significant
of various
that
configuration
or by replacement
affected
of the Cotton
and arabinose.
the Cotton
not
as with
ring
to the optical
ring
of a In the
is probable
by the presence
on the Cotton
in either
as already
configuration it
to be general
and guanosine
influence
The magnitude substitution
effect
the corresponding
derivatives
Cotton
the same in a-D-
ring,
by
at c-l',
a positive
was positive;
in the sugar is also
configuration
had the opposite
influenced
It
by H or Cl.
substituents
Cotton
is
influenced
effect).
prove
atom is
is
gives
effect
will
effect
by formation
of the Cotton
of the sugar
most of these
in the m-conformation
the sugar
(p-L-adenosine)
for
effect
50-110.
of the Cotton
the nucleoside
of the Cotton
nucleosides;
in the range
factors:
ring
'ihe magnitude
rotations.
in pyrimidine
is
that
2) fixing
noted; third
than
the amplitude We find
the
small
AND BIOPHYSICAL RESEARCH COhtMUNlCATlONS
slightly
were
found
ribose,
p-nucleosides,
et al,
by
differences
including
higher
influenced
Pt-deozyribose,
the amplitude
in arabinosides
than
of
in ribosides
1966).
are related
to the oonfoxmation
to the asymmetry
506
in the sugar,
of the as suggested
BIOCHEMICAL
Vol. 22, No. 5, 1966
AND BIOPHYSICAL RESEARCH COMMUNICATIONS
for p,yrimidine nucleosides (Ulbricht rotation
and the insensitivity
et al, 1965,
1966),
to the configuration
Whereas, in pyrimidine nucleosides, steric groups on C-2' (and, to a lesser extent,
then the lower
at C-21 is understandable.
interaction
between the
those on C-5') and substituents
in position
2 of the pyrimidine ring (such as the carbonyl
effeotively
prevent free rotation
interaction
is greatly
(II)
atom.
The latter
forms will be small.
favoured, e.g., It
bona, such
reduced or absent in purines (Donahue and Trueblood,
Consequently the energy difference
1960).
&
about the glycosidic
group)
by electronic
between the m conformation will
(I)
and still
be
repulsion between N3 and the ring oxygen
is, of course, the &
conformation which is found in DNA,
in AMP (Kraut and Jensen, 1964) and in almost all
crystalline
nucleosides
(Sundaralingam and Jensen, 1965).
MO
OH
OM
Ho
I
II
The results obtained with c.vclQnucleosides, in which the conformation is fixed by formation of a third ring, interest.
Thus 8,5(-cycloadenosine
are of particular
(III)
(Xmx , 264 w), in which the . a&& conformation is fixed by a ring linking C-5' of the sugar to C-8 in the imidazole ring, has a negative Cotton effect
like other purine
P-nucleosides, but of larger amplitude (a - -183). 2~,:i1-isopropylidene-~3,5~-cycloadenosine which necessarily has the m effsct
iodide (IV)
On the other hand, (hmax., 272 q),
conformation, has a small positive
(a - +Yt) (see Figure 1).
Cotton
From other examples we know that the
507
BlOCHEMlCAL
Vol. 22, No. 5, 1966
isopropylidene
AND BIOPHYSICAL RESEARCH COMMUNICATIONS
group has no effect
on the sign of the ORD, and it should
the also be noted that theh max. of both cyclonucleasides falls *thin Rowever, in the cese of range of the compoundsstudied (248-279 w)+ the g3,5\-cyclonucleoside,
the possibility
that a change in the
chromophore is responsible for the change in sign cannot be excluded,
I-
IV
III The interpretation unsubstituted the first
of the curves given by giycosides of
purine (see fig.
2) is madedifficult
by the fact that
peak in the OEDcurve occurs at a wave-length very close to
theh max. (265 w)a
This suggests that this maximumin the U.V, is
due to an overlap of the absorption due to two transitions, of which is optically
active.
If the optically
at a wave-length lower the..nh-.,
the first
active
only one
transition
Cotton effect
were
would be
positive;
if it were at a wave-length higher thanAm= . , the first Cotton effect would be negative, The latter would be in accord with the results for substituted
of the transition
purine P-nucleosides, but since the direction
momentmay be different,
will not necessarily be the seme. the first
the sign of the Cotton effect
The absence of a real trough before
peek is reached suggests that the first
Cotton
effect
mey be
positive. It will
be noted that these unsubstituted
have two Cotton effects,
purine nucleosides
the second being negative.
one or both extreme of this second Cotton effect
508
Wehave observed
in a number of other
Vol. 22, No. 5, 1966
BIOCHEMICAL
*lo'-
:
AND BIOPHYSICAL RESEARCH COMMUNICATIONS
1."'1""1““1'
-4-6-
:
-a-lO-
I 250
200
i : / ] i ::: .:’ ‘.I ,..I....
solvent:
water I . . . . I 455 350
305 XCmp)
Fig.
1. ORD curves
of adenosine
8,5'-cycloadenosine tadenosine
iodide
(-);
(..**a*);
(-em*-
Sazaadenosine
*a*).
.-
/
HO
HP
250
-3 r HO
OH
200
(-a-*);
2',31-isopropylidene-N3,5'-cyclo-
-3
300
h(m$
350
2. OFtD curves of the J3-riboside, 2'4eoxyriboside and erabinoside of unsubstituted purine.
Fig.
nucleosicles in which measurementswere satisfactorily wave-lengths, e.g. 8-aaaadenosine (fig. 6-chloropurine.
l),
and various derivatives
The sign of the second Cotton effect
always negative in p-anomers (it
has
not
so far available).
509
extended to low of
appears to be
been observed in the wsnomers
BIOCHEMICAL
Vol. 22, No. 5, 1966
ORD measurements
were made with
Spectropolarimeter
"Polarmatic
rricsson (and
a few methanolic)
more than
solutions
the Bellingham '62"
(with
and Stanley/Bendix-
at room-temperature
an optical
density
on
aqueous
ath max. of not
2). It
elsewhere,
AND BIOPHYSICAL RESEARCH COMMUNICATIONS
is hoped
to publish
together
with
who have supplied
us with
1V.R. Lee and E.M. Acton to whoiomwe are particularly
full
a full
details
of these
scknowledgement
compounds. and their
results
to the msny kind
Many were
associates
and other
the gift
at Stanford
of Drs. Research
individuals L. Goodman, Institute,
indebted.
References and Trueblood, K.N., J. Mol. Biol., 1, 363 (1960), Donahue,.J., T.L.V., Chem. & Ind., 212 (1964). Emerson, T-R., and Ulbricht, &, 79 (1964 s . Kraut, J., and Jensen, L.H., Acta Cryst., Sundsralingam, M., end Jensen, L.H., J. Mol. Biol., u, 914, 930 (1965). Ulbricht, T.L.V., Jennings, J.P., Scopes, P.%, and Klyne, W., Tetrahedron Letters, 695 (1964). Ulbricht, T.L.V., Emerson, T.R., and Swan, R.J., Biochem. Biophys. Res. Comm., u, 643 0965). Ulbricht, T.L.V., Emerson, T-R., and Swan, R.J., Tetrahedron Letters, in press.
510
Vol. 22, No. 5, 1966
AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Dispersion of Purine Nucleosides'
B
T.R. Emerson, R.J. Swan and T.L.V. Ulbricht Xestfield
College, London, England and
Twyford Laboratories,
London, Englend
ReceivedJanuary 25, 1966 we have previously
reported that the Optical Rotatory Dispersion
(ORD) curves of a-purine nucleosides give positive the p-anomers give negative Cotton effects purine ~y-nucleosides 1964).
(Ulbricht
obey Hudson's Isorotation
Recently we presented preliminary
nucleosides, indicating
Cotton effects,
whereas
et al, 1964);
hence
Rules (Emerson and Ulbricht,
results
on a series of pyrimidine
that the sign and magnitude of the long wave-length
Cotton effects produced by these compoundscould be related to their conformation (Ulbricht
et al, 1965).
Further studies have confirmed these
conclusions and have madeit possible to propose a rule for predicting
the
sign of the Cotton effect
et al,
1966).
in pyrimidine
Wehave now examined fifty
results with E9-glycosides, nucleosides.
purine nucleosides, and report here our
including
cvclo-nucleosides
is excluded.
In many cases, complete ORDcurves are more difficult
purine nucleosides absorb intensely the use of very dilute
* Optical Rotatory Part IV: T.L.V. ai Dress.
aromatic
groups, which can influence the sign of the Cotton
to obtain with purine than with pyrimidine nucleosides.
necessitating
and azapurine
Consideration of compoundscontaining additional
systems (e.g. p-toluoyl Effect)
fursnose nucleosides (Ulbricht
in the ultra-violet
This is because (high e values),
solutions in the region near-h max.'
Dispersion of Nucleic Acid Derivatives, part V. Ulbricht, R.J. Swan& A.&i. Wchelson, Chem. Commun.,
505
BIOCHEMICAL
Vol. 22, No. 5, 1966
and because is
they
noticeably
purines
have
lower
following
the &g~
1) the anomeric
(N3,5'-cycloadenosine
one nucleoside
in which
the Cotton
relation
sign
of the
(D- or L-)
at the anomeric
carbon
The sign isopropylidene group
not
groups
position
in
the purine
8 in the heterocyclic effects
like
of adenosine
nucleosides
- suggesting,
has no major
between xylose
derivatives
(Ulbricht
effect et al,
If chromophore
1965;
Emerson
such ORD results with
by substitution
nucleus
(+azapurine
reference
the
stereochemistry
of acetyl
or of the 2'-OH of the
of N for
CH at
nucleosides
purinea).
give
The tri-O-acetyl
give
similar
curves
the pyrimidines,
that
to the parent
hydrogen-bonding
effect. effect
sugars,
considerably
this
as in P-L-compounds.
nor
In pyrimidine is
, since
by the nature
is
but no significant
of various
that
configuration
or by replacement
affected
of the Cotton
and arabinose.
the Cotton
not
as with
ring
to the optical
ring
of a In the
is probable
by the presence
on the Cotton
in either
as already
configuration it
to be general
and guanosine
influence
The magnitude substitution
effect
the corresponding
derivatives
Cotton
the same in a-D-
ring,
by
at c-l',
a positive
was positive;
in the sugar is also
configuration
had the opposite
influenced
It
by H or Cl.
substituents
Cotton
is
influenced
effect).
prove
atom is
is
gives
effect
will
effect
by formation
of the Cotton
of the sugar
most of these
in the m-conformation
the sugar
(p-L-adenosine)
for
effect
50-110.
of the Cotton
the nucleoside
of the Cotton
nucleosides;
in the range
factors:
ring
'ihe magnitude
rotations.
in pyrimidine
is
that
2) fixing
noted; third
than
the amplitude We find
the
small
AND BIOPHYSICAL RESEARCH COhtMUNlCATlONS
slightly
were
found
ribose,
p-nucleosides,
et al,
by
differences
including
higher
influenced
Pt-deozyribose,
the amplitude
in arabinosides
than
of
in ribosides
1966).
are related
to the oonfoxmation
to the asymmetry
506
in the sugar,
of the as suggested
BIOCHEMICAL
Vol. 22, No. 5, 1966
AND BIOPHYSICAL RESEARCH COMMUNICATIONS
for p,yrimidine nucleosides (Ulbricht rotation
and the insensitivity
et al, 1965,
1966),
to the configuration
Whereas, in pyrimidine nucleosides, steric groups on C-2' (and, to a lesser extent,
then the lower
at C-21 is understandable.
interaction
between the
those on C-5') and substituents
in position
2 of the pyrimidine ring (such as the carbonyl
effeotively
prevent free rotation
interaction
is greatly
(II)
atom.
The latter
forms will be small.
favoured, e.g., It
bona, such
reduced or absent in purines (Donahue and Trueblood,
Consequently the energy difference
1960).
&
about the glycosidic
group)
by electronic
between the m conformation will
(I)
and still
be
repulsion between N3 and the ring oxygen
is, of course, the &
conformation which is found in DNA,
in AMP (Kraut and Jensen, 1964) and in almost all
crystalline
nucleosides
(Sundaralingam and Jensen, 1965).
MO
OH
OM
Ho
I
II
The results obtained with c.vclQnucleosides, in which the conformation is fixed by formation of a third ring, interest.
Thus 8,5(-cycloadenosine
are of particular
(III)
(Xmx , 264 w), in which the . a&& conformation is fixed by a ring linking C-5' of the sugar to C-8 in the imidazole ring, has a negative Cotton effect
like other purine
P-nucleosides, but of larger amplitude (a - -183). 2~,:i1-isopropylidene-~3,5~-cycloadenosine which necessarily has the m effsct
iodide (IV)
On the other hand, (hmax., 272 q),
conformation, has a small positive
(a - +Yt) (see Figure 1).
Cotton
From other examples we know that the
507
BlOCHEMlCAL
Vol. 22, No. 5, 1966
isopropylidene
AND BIOPHYSICAL RESEARCH COMMUNICATIONS
group has no effect
on the sign of the ORD, and it should
the also be noted that theh max. of both cyclonucleasides falls *thin Rowever, in the cese of range of the compoundsstudied (248-279 w)+ the g3,5\-cyclonucleoside,
the possibility
that a change in the
chromophore is responsible for the change in sign cannot be excluded,
I-
IV
III The interpretation unsubstituted the first
of the curves given by giycosides of
purine (see fig.
2) is madedifficult
by the fact that
peak in the OEDcurve occurs at a wave-length very close to
theh max. (265 w)a
This suggests that this maximumin the U.V, is
due to an overlap of the absorption due to two transitions, of which is optically
active.
If the optically
at a wave-length lower the..nh-.,
the first
active
only one
transition
Cotton effect
were
would be
positive;
if it were at a wave-length higher thanAm= . , the first Cotton effect would be negative, The latter would be in accord with the results for substituted
of the transition
purine P-nucleosides, but since the direction
momentmay be different,
will not necessarily be the seme. the first
the sign of the Cotton effect
The absence of a real trough before
peek is reached suggests that the first
Cotton
effect
mey be
positive. It will
be noted that these unsubstituted
have two Cotton effects,
purine nucleosides
the second being negative.
one or both extreme of this second Cotton effect
508
Wehave observed
in a number of other
Vol. 22, No. 5, 1966
BIOCHEMICAL
*lo'-
:
AND BIOPHYSICAL RESEARCH COMMUNICATIONS
1."'1""1““1'
-4-6-
:
-a-lO-
I 250
200
i : / ] i ::: .:’ ‘.I ,..I....
solvent:
water I . . . . I 455 350
305 XCmp)
Fig.
1. ORD curves
of adenosine
8,5'-cycloadenosine tadenosine
iodide
(-);
(..**a*);
(-em*-
Sazaadenosine
*a*).
.-
/
HO
HP
250
-3 r HO
OH
200
(-a-*);
2',31-isopropylidene-N3,5'-cyclo-
-3
300
h(m$
350
2. OFtD curves of the J3-riboside, 2'4eoxyriboside and erabinoside of unsubstituted purine.
Fig.
nucleosicles in which measurementswere satisfactorily wave-lengths, e.g. 8-aaaadenosine (fig. 6-chloropurine.
l),
and various derivatives
The sign of the second Cotton effect
always negative in p-anomers (it
has
not
so far available).
509
extended to low of
appears to be
been observed in the wsnomers
BIOCHEMICAL
Vol. 22, No. 5, 1966
ORD measurements
were made with
Spectropolarimeter
"Polarmatic
rricsson (and
a few methanolic)
more than
solutions
the Bellingham '62"
(with
and Stanley/Bendix-
at room-temperature
an optical
density
on
aqueous
ath max. of not
2). It
elsewhere,
AND BIOPHYSICAL RESEARCH COMMUNICATIONS
is hoped
to publish
together
with
who have supplied
us with
1V.R. Lee and E.M. Acton to whoiomwe are particularly
full
a full
details
of these
scknowledgement
compounds. and their
results
to the msny kind
Many were
associates
and other
the gift
at Stanford
of Drs. Research
individuals L. Goodman, Institute,
indebted.
References and Trueblood, K.N., J. Mol. Biol., 1, 363 (1960), Donahue,.J., T.L.V., Chem. & Ind., 212 (1964). Emerson, T-R., and Ulbricht, &, 79 (1964 s . Kraut, J., and Jensen, L.H., Acta Cryst., Sundsralingam, M., end Jensen, L.H., J. Mol. Biol., u, 914, 930 (1965). Ulbricht, T.L.V., Jennings, J.P., Scopes, P.%, and Klyne, W., Tetrahedron Letters, 695 (1964). Ulbricht, T.L.V., Emerson, T.R., and Swan, R.J., Biochem. Biophys. Res. Comm., u, 643 0965). Ulbricht, T.L.V., Emerson, T-R., and Swan, R.J., Tetrahedron Letters, in press.
510