π-Interactions of modified nucleobases. On mesomeric purine betaines with inversed charge properties

Article abstract of DOI:10.1246/bcsj.74.2379

Intermolecular interactions of modified nucleobases with altered charge properties in relation to natural systems are studied. We prepared conjugated mesomeric betaines of purines and examined their properties by semiempirical calculations, ^IH

Full text of DOI:10.1246/bcsj.74.2379

Bull. Chem.
Soc. Jpn.
74
12
© 2001 The Chemical Society of Japan
Bull. Chem. Soc. Jpn., 74, 2379–2384 (2001) 2379
The Chemical
Society of Ja-
pan
The Chemical
Society of Ja-
π
-Interactions of Modified Nucleobases. On Mesomeric Purine Betaines
with Inversed Charge Properties.
pan
OB
12
15
π-Interactions of Modified Nucleobases
A. Schmidt et al.
Andreas Schmidt*,# and Markus Karl Kindermann†
2001
2379
2384
BCSJA8
0009-2673
01075
3
Technische Universität Clausthal, Institut für Organische Chemie, Leibnizstraße 6, D-38678 Clausthal-Zellerfeld,
Germany
†Ernst-Moritz-Arndt-Universität Greifswald, Institut für Chemie und Biochemie, Soldmannstrasse 16,
D-17487 Greifswald, Germany
(Received March 8, 2001)
8
2001
6
20
Intermolecular interactions of modified nucleobases with altered charge properties in relation to natural systems are
studied. We prepared conjugated mesomeric betaines of purines and examined their properties by semiempirical calcula-
tions, 1H NMR titrations and ESI mass spectrometry. Thus, nucleophilic substitutions of 4-(dimethylamino)pyridine and
pyridine, respectively, on 2-amino-6-chloropurine 1 and 2,6-dichloropurine 2 resulted in the formation of purin-6-yl
hetarenium salts 3–6. These were converted into the conjugated mesomeric betaines 7–10, respectively, on treatment
with the anion exchange resin Amberlite® IRA-400 in its hydroxy form. The betaines 7–10 possess umpoled purine rings
in relation to 7-methylguanine that forms the betainic 5ꢀ-cap structure of m-RNA. We studied the π-stacking interactions
of the conjugated mesomeric betaine 8 and of its cationic precursor 4 with L-tryptophan, adenine, adenosine, and gua-
nosine in deuterated water.
2001
4.8.3
4.9.5
During recent decades, several mesomeric betaines have
been isolated from natural sources,1 including biologically
highly active alkaloids such as norzooanemonine,2 matadine,3
serpentine,4 and ungerimine.5 Among the modified nucleobas-
es, the mesomeric betaine 7-methylguanine (m7G) is known to
be present in tRNA molecules and has been identified as 5ꢀ-ter-
minal cap-structure of eucaryotic viral and cellular mRNA.6
Numerous efforts have been devoted to the elucidation of its
biological function. Stabilizing effects as well as betaine–pro-
tein molecular recognition to enable the binding of the mRNA
molecules to proteins on the surface of the ribosomes prior to
the initiation of translation have been discussed.7 In general,
to explain the chemical specifity that guarantees molecular rec-
ognition, the influence of π–π stacking by frontier orbital inter-
actions,8 π–σ attractions that overcome π–π attractions,9 as
well as electrostatic interactions involving the out-of-plane π-
electron density10 have been presented. Base-mispairing in-
duced by 7-methylguanine causes its mutagenicity,11 and it
was surprisingly identified as one of the main metabolites on
treatment of DNA with carcinogens such as hydrazine.12 Fur-
thermore, model systems of m7G are self-complementary at
physiological pH. The biological role of this phenomenon still
remains uncertain.13
curring m7G that possesses positive substituents at C-4 instead
of the 4-olate moiety, and a negative charge delocalized in the
purin ring system. In view of their interesting biological prop-
erties, pyridinium rings seemed to be suitable cationic partial
structures of the target nucleobase betaines. In continuation of
our interest in the chemistry of nucleobases14 and betaine
derivatives15 we report here the syntheses and the intermolecu-
lar interactions of those systems.
Results and Discussion
Syntheses. We chose 2-amino-6-chloropurine 1, the iso-
mer of the cytotoxic natural alkaloid trachycladine A from Tra-
chycladus laevispirulifer,16 and 2,6-dichloropurine 2 as suit-
able starting materials for betaine formation. The betaines
were smoothly formed by a two-step procedure. Thus, nucleo-
philic displacement on the purines, respectively, by pyridine or
4-(dimethylamino)pyridine in chlorobenzene gave the 1-(pu-
rin-6-yl)pyridinium salts 3–6 in high yields and as single tau-
tomers, respectively. Aqueous solutions of 3–6 were passed
through the anion exchange resin Amberlite® IRA-400 in its
hydroxy form. Concentration of the elutes at ambient temper-
ature in vacuo yielded the (6-pyridinio)purinates 7–10, respec-
tively, as intensely orange colored compounds which could be
protonated to the starting materials by hydrochloric acid.17 For
the case of 3, attempts to deprotonate with hydroxide gave
guanine 11 and glutaconaldehyde 12, as a result of pericyclic
ring cleavage at C-2 of the pyridinium ring and subsequent
substitution of the resulting penta-1,3-dienal derivative
(Scheme 1). In contrast to this, the 4-(dimethylamino)pyridin-
ium derivative 4 proved to be stable towards ring opening and
gave the betaine 8 in nearly quantitative yield on treatment
We currently are interested in studying mesomeric betaines
with different types of conjugation and isoconjugate relation-
ships within a given nucleobase skeleton in order to gain in-
sights into the role of charge distribution on molecular recog-
nition. Therefore, we prepared guanine derivatives with in-
versed charged properties for comparison to the naturally oc-
# Former address: Emory University, Department of Chemistry,
1515 Pierce Drive, Atlanta, Georgia 30322, USA.

2380 Bull. Chem. Soc. Jpn., 74, No. 12 (2001)
π-Interactions of Modified Nucleobases
Fig. 1.
Scheme 1.
with OH−. Under the applied reaction conditions, no disubsti-
tution of 2,6-dichloropurine 2 with the heteroaromatics to di-
cationic species was observed.
The mRNA nucleobase m7G as well as 7–10 belong to the
class of conjugated heterocyclic betaines (CMB). Characteris-
tically, the charges are in mutual conjugation, so that common
sites for either positive and negative charge exist in the canoni-
cal formulae. However, the molecules are members of differ-
ent subclasses of conjugated mesomeric betaines, sixteen of
which can be distinguished by their isoconjugate relation-
ships.18 Whereas m7G is isoconjugate with the even non-alter-
nant hydrocarbon dianion Ⅰ and thus belongs to class 4 of me-
someric betaines, 3–6 are heterocyclic N-ylides isoconjugate to
the odd non-alternant hydrocarbon anion Ⅱ (class 6) (Fig. 1).
As outlined in Fig. 2, the canonical formulae as well as the
PM3 calculation predict inversed atomic charges of the purine
moieties in m7G and 8 and the umpolung of C(6), N(7), and
N(9).
Fig. 2.
tween phenylalanyl-tRNA and synthetase-tRNA19 or glutamate
dehydrogenase and ADP,20 is known to have the best π-donat-
ing character among the aromatic amino acids.21 Therefore,
the examination of electronically inversed guanine betaines
could provide valuable insights into the role of charge distribu-
tion on mutual recognition of molecules. Semiempirical cal-
culations applying PM3 parameters predict profound differ-
ences in the frontier orbitals.22 The HOMO [IP(PM3) =
−8.18 eV] of the planar m7G is essentially located at N(1),
N(3), C(5), and O(13), i.e. in the pyrimidine moiety of the pu-
rine skeleton, whereas the LUMO [IP(PM3) = −0.92 eV] has
its largest coefficients at N(7), C(8), and N(9) in the imidazole
ring. In contrast to this, the HOMO of the betaine 8 [IP(PM3)
= −7.77 eV] has its largest coefficients at the exocyclic amino
nitrogen atom, at C(6) and at N(7), whereas the LUMO
[IP(PM3) = −1.97 eV] is essentially located at the nitrogen
The frontier orbital profile of the m7G/L-trp system seems to
be responsible for the interaction of the 5ꢀ-cap structure to the
binding protein of the ribosom prior to the initiation of transla-
tion. L-tryptophan, which is preferentially involved in π–π-
stacking interactions of proteins with nucleic acids such as be-

A. Schmidt et al.
Bull. Chem. Soc. Jpn., 74, No. 12 (2001) 2381
Fig. 3.
atoms and the α- and γ-carbon atoms of the pyridinium ring
(Fig. 3). According to the PM3 calculation and in agreement
with the classification of 8 as a conjugated mesomeric betaine
(CMB), the most stable conformation is the planar one [∆Hf =
488.89 kJ]. The purine and pyridinium rings are joined
through a σ-bond at an active position of the HOMO. The
semiempirically calculated permanent dipole moments in the
ground states of m7G and 825 are presented in Fig. 3 in correct
size and direction. Dipole–dipole interactions are known to
contribute to specifying the mutual orientation of molecules in
stacks.26
Scheme 2.
be reduced due to the instability of adenosine and guanosine
toward bases. But, upfield shifts of the 1H NMR signals attrib-
utable to π-stacking interactions between the betaine 4 and the
anions of L-tryptophan and adenine are observable. The chem-
ical shift changes can be explained by ring-current effects that
exert a shielding of the protons in vertical position in relation
to the aromatic system.28
In agreement with the expectation of better π-acceptor capa-
bilities due to a decreased LUMO energy and in accord with
observations with adenine,26 stronger interactions were ob-
served with the cationic purine nucleobase 4. Thus, on treat-
ment of a 10 mM solution of the cation 4 with a 10 mM solu-
tion of L-trp and adenine in D2O all the resonance frequencies
shift characteristically upfield, consistent with the formation of
π-stacked associates (Table 1). It is apparent that the chemical
shift changes of tryptophan on addition of guanine are 2.0 to
2.4-fold larger than those documented for the natural m7G–L-
trp π-interaction, which is presumably responsible for the
binding of the mRNA to the ribosome.8 On the other hand, the
purine 4/L-trp system is an intermolecular stacking model for
π-electron donor/pyridinium coenzyme interactions.27
We performed NMR titrations in order to elucidate the pos-
sible geometries of the π-stacked associates (Fig. 4). In agree-
ment with the formation of π-complexes, the indole protons of
the L-trp are shifted to a larger extent than the amino acid resi-
due, indicative of a stacking of the whole aromatic system not
involving the side chain. Indeeed, the largest differences in
proton chemical shifts of the cation 4 are observed in the α-po-
sitions of the pyridinium moiety. At these positions, the PM3-
calculated LUMO has its largest coefficients.
π
-Stacking Interactions in D2O. At first, we examined
the interactions of cationic purine derivative 4 and of the be-
tainic purine derivative 8 as model substances with L-tryp-
tophan in deuterated water by means of 1H NMR spectroscopy.
In view of the expected inversed π-electron donor–acceptor
capabilities of the purine in relation to the natural system, and
the biological importance of charge-transfer interactions of π-
donor molecules to pyridinium coenzymes,27 we performed
additional measurements with adenine, adenosine, and gua-
nosine. Due to the limited solubility of guanine in water at pH
7 we were prevented from measurements using this nucleo-
base. The chemical shift changes are presented in Table 1.
On addition of L-tryptophan, adenine, adenosine, and gua-
nosine to a solution of the mesomeric betaine 8 in D2O, con-
siderable downfield shifts of the pyridiniopurinate protons can
be observed, while the substrate’s protons shift upfield. In
D2O, quantitative salt formation of 8 to 13–16 unambigously
occurs (Scheme 2), each salt consisting of the cationic part of 4
and the monoanions of L-tryptophan, adenine, adenosine, and
guanosine, respectively. Adenine is known to be deprotonated
at N(9), whereas deprotonation of guanosine occurs at N(1)
and of adenosine at the secondary hydroxyl group of the ribose
moiety.28 In agreement with the salt formation, on addition of
the substrates, decolorization of the betaine 8 from intense or-
ange-yellow to pale yellow (4) is observable.
Thus, the effects of possible π-stacking interactions of the
1
betaine 8 and the substrates on the H NMR spectra were su-
perseded and could not be estimated for that reason. There-
fore, we undertook measurements in 0.1 M NaOD in D2O to
avoid salt formation; however, the variety of substrates was to
π-Interactions were also observed on addition of adenine to
4 (Table 1.). Quaternization of adenine to adeninium is essen-

2382 Bull. Chem. Soc. Jpn., 74, No. 12 (2001)
π-Interactions of Modified Nucleobases
Table 1. Chemical Shifts Changes of the Cationic Guanine 4 and the Mesomeric Betaine 8 on Addition of L-Tryptophan (trp),
Adenine (ade), Adenosine (ado), and Guanosine (guo) in D2O, and of 8 in 0.1 M NaOD in D2O, at 300 MHz and 25 °C,
Respectively. Chemical Shift Changes ∆δ are Given in ppm. Concentration of 4 and 8 in D2O: 10 mM
∆δ of the guanines
∆δ of the substrates
5-H 6-H
−0.14 −0.17 −0.15 −0.14 −0.17
Guanine Substr.
trp
α-H
β-H
8-H
2-H
4-H
7-H
8-H
—
−0.11
−0.13
−0.02
−0.04
−0.11
−0.01
−0.01
−0.10
0
4
ade
ado
guo
trp
−0.15
−0.13
—
—
—
—
—
—
—
—
—
—
—
—
—
−0.15
−0.07
−0.09
—
in D2O
+0.07a)
+0.27
+0.44
+0.23
+0.43
−0.06
−0.35
+0.05a)
+0.45
+0.71
+0.41
+0.71
−0.08
−0.20
+0.04a)
+0.18
n.d.b)
−0.05 −0.04 −0.05 −0.05 −0.06
8
ade
ado
guo
trp
+0.06
−0.15
—
—
—
—
—
—
—
—
—
—
—
—
—
+0.08
−0.08
−0.12
—
in D2O
+0.11
+0.16
−0.02
−0.07
8c)
−0.01 −0.01 −0.01 −0.01 −0.01
−0.01
in NaOD
ade
—
—
—
—
−0.01
n.d.: not detectable. a) broadened signals due to precipitation during the NMR measurement. b) overlapped. c) measured
in 0.1 M NaOD in D2O; ado and guo are not stable toward NaOD, 4 gives 8.
Fig. 4. 1H NMR titrations of cation 4 with L-tryptophan.

A. Schmidt et al.
Bull. Chem. Soc. Jpn., 74, No. 12 (2001) 2383
cm−1; 1H NMR (300 MHz, DMSO-d6; Me4Si) δ 7.21 (2H, s), 8.44
(2H, m), 8.48 (1H, s), 8.91 (1H, tt, J = 6.3 and 5.7 Hz), 10.10 (2H,
d, J = 5.7 Hz), and 13.54 (1H, s); 13C NMR (75 MHz, DMSO-d6;
Me4Si) δ 116.83, 127.87, 142.44, 144.44, 145.70, 149.42, 158.80,
and 159.48; MS m/z (FAB, mNBA) 213.9 (M+, 41) and 77.3
(100).
tial for the formation of π-stacks with indole, due to a consid-
erable lowering of the LUMO energy.26,28 As all resonance fre-
quencies shift upfield on addition of 4 to adenine and vice ver-
sa, no acid-base reaction such as 4 + ade → 8 + adeH+ takes
place. Thus, in contrast to observed stacking interactions to in-
dole derivatives,27 the adenine apparently is the π-donor mole-
cule of the interaction. On titrating the cation 4 to a 10 mM so-
lution of adenine in D2O at rt, the resonance frequencies of 2-
H are shifted to a larger extent than those at the 8-H position.
Chemical shift changes on treatment the solutions of 4 with
adenosine and guanosine, respectively, are small.
The specific architecture prevents 4 and 8 from forming
Watson–Crick or wobble base pairs. In principle, only Hoogs-
teen-type base pairing is possible, due to steric reasons. How-
ever, in DMSO-d6-solution, no hydrogen bonds of the mesom-
eric betaine 8 to adenine, adenosine, guanine, or guanosine
could be observed. The resonance frequencies of 1 : 1 mix-
tures correspond to the chemical shifts of the pure compounds
under analogous reaction conditions. Obviously, substitution
of the olate group by an hetarenium substituent and concomi-
tant umpolung of the purine skeleton causes a complete loss of
hydrogen-bonding capabilities. In accordance with the NMR
measurements and in contrast to our earlier results obtained
with uracil betaines,14 no hydrogen bonded homo-intermolecu-
lar associates were detectable by electrospray ionization mass
spectrometry (ESIMS) in anhydrous MeCN. In contrast to the
5ꢀ-cap structure of mRNA, derivative 8 is obviously not self-
complementary. The reason for that is the direct consequence
of the altered charge properties in comparison to the natural
analogue m7G, as no coupling of the permanent dipole mo-
ments by forming a centrosymmetric hydrogen-bonded dimer
is possible.
1-(2-Amino-purin-6-yl)-4-dimethylaminopyridinium Chlo-
ride 4. 0.85 g (5.0 mmol) of 2-amino-6-chloropurine 1 were
suspended in 50 mL of chlorobenzene. Then, 0.61 g (5.0 mmol)
of 4-(dimethylamino)pyridine was added and the reaction mixture
was heated at reflux temperature over a period of 24 h (tlc). After
cooling, the yellow precipitate was filtered off, washed with ethyl
acetate and recrystallized (0.99 g, 69%), mp > 300 °C (from etha-
nol–water) Found: C, 49.40; H, 5.06; N, 33.36%. Calcd for
C12H14ClN7: C, 49.40; H, 4.83; N, 33.61%. UV: compd is not sol-
uble in CH2Cl2; UV λmax(MeCN)/nm 350.8, 313.6, and 220.1 nm;
λ
max(MeOH)/nm 352.9, 307.9, and 220.6; IR 3422, 3309, 3195,
3073, 2995, 1661, 1637, 1591, 1567, 1518, 1473, 1401, 1375,
1305, 1211, 1158, 816, and 748 cm−1 1H NMR (300 MHz,
;
DMSO-d6; Me4Si) δ 3.35 (6H, s), 6.93 (2H, s), 7.31 (2H, d, J =
8.4 Hz), 8.29 (1H, s), 9.47 (2H, d, J = 8.4 Hz); 13C NMR (75
MHz, DMSO-d6; Me4Si) δ 40.31, 107.61, 115.41, 137.91, 142.42,
145.32, 156.97, 157.86, and 159.36; MS m/z (FAB, mNBA) 257.2
(M++1, 100).
1-(2-Chloro-purin-6-yl)pyridinium Chloride 5. A suspen-
sion of 0.94 g (5.0 mmol) 2,6-dichloropurine 2 in 50 mL of anhy-
drous pyridine was heated at reflux temperature for 3 h. After
cooling, the precipitated solid was filtered off and recrystallized
(0.76 g, 57%), mp > 300 °C (from EtOH) Found: C, 44.34; H,
3.31; N, 25.14%. Calcd for C10H7Cl2N5: C, 44.79; H, 2.63; N,
26.12%; UV λmax(MeOH)/nm 451.4. 316.14. 270.0, and 221.5; IR
3049, 2868, 2747, 1633, 1617, 1574, 1561, 1499, 1361, 1318,
1187, 992, 923, 881, and 671 cm−1; 1H NMR (300 MHz, DMSO-
d6; Me4Si) δ 8.48 (2H, dd, J = 7.5 Hz), 8.99 (1H, tt, J = 7.8 and
1.2 Hz), 9.09 (1H, s), 10.14 (2H, d, J = 5.7 Hz).
1-(2-Chloro-purin-6-yl)4-dimethylaminopyridinium Chlo-
ride 6. A suspension of 0.94 g (5.0 mmol) of 2,6-dichloropurine
2 in 50 mL of ethyl acetate was treated with 0.61 g (5.0 mmol) of
4-(dimethylamino)pyridine and heated at reflux temperature for 7
h. After cooling, the resulting precipitate was filtered off, washed
with ethyl acetate and recrystallized (0.92 g, 62%), mp > 300 °C
(from EtOH) Found: C, 44.91; H, 4.42; N, 25.69%. Calcd for
C12H12N5Cl2•H2O: C, 45.73; H, 4.47; N, 22.22%; UV
Experimental
General Methods. The NMR spectra were acquired on a
Bruker ARX 300. Me4Si was used as internal standard. IR spec-
tra were obtained on a Nicolet 205 and were determined on pellets
(2.5% in KBr). FAB mass spectra were recorded on an AMD M-
40 (AMD Intectra GmbH Harbstedt) in positive ion detection
mode in mNBA. ESI mass spectra were taken on a Hewlett-Pack-
ard Series 1100 LC/MSD. All samples were dried for at least 24 h
at 80 °C. However, in accordance with known hetarenium com-
pounds and X-ray crystallographic results,14,15 some of the com-
pounds crystallize with varying amounts of water. Therefore, the
UV spectra were measured qualitatively with a Perkin Elmer UV/
VIS/NIR spectrometer Lambda 19, because the water of hydration
causes some changes in solvent polarity. All melting points were
determined on a Boëtius melting apparatus; the values reported
are uncorrected.
1-(2-Amino-purin-6-yl)pyridinium Chloride 3. 0.85 g (5.0
mmol) 2-amino-6-chloropurine 1 were suspended in 50 mL of py-
ridine and were heated at reflux temperature for 5 h. After cool-
ing, the resulting yellow-brownish precipitate was filtered off,
washed with ethyl acetate and recrystallized (0.86 g, 81%), mp >
300 °C (from EtOH–H2O) Found: C, 48.35; H, 4.08; N, 33.61%.
Calcd for C10H9N6•2H2O: C, 48.19; H, 5.26; N, 33.72%; UV:
compd is not soluble in dichloromethane; UV λmax(MeCN)/nm
383.7 and 266.4; λmax(MeOH)/nm 393.0, 267.6, and 228.4; IR
3421, 3311, 3200, 3059, 2897, 2758, 1638, 1572, 1556, 1519,
1470, 1368, 1299, 1204, 1152, 933, 903, 777, 675, 626, and 552
λ
max(MeCN)/nm 351.1, 338.0, and 279.1; IR 3056, 1656, 1590,
1
1562, 1377, 1312, 1228, 1179, 1141, 1125, and 985 cm−1; H
NMR (300 MHz, DMSO-d6; Me4Si) δ 7.34 (2H, d, J = 8.2 Hz),
8.65 (1H, s), 9.56 (2H, d, J = 8.2 Hz).
General Procedure for the Synthesis of the Mesomeric Be-
taines 7–10. 50 mL of the anion exchange resin Amberlite®
IRA-400 were washed with 2 L of water and then filled into a col-
umn without frit (height: 16 cm; diameter: 3 cm). Then, the resin
was treated with 10% aqueous sodium hydroxide over a period of
45 min. Then, the base was rinsed out by water to pH 7 of the
elute and a sample of the purinyl salts in 20 mL of water were giv-
en on the resin. Each aqueous elute were concentrated in vacuo to
yield its analytically pure betaine.
2-Amino-6-(1-pyridinio)purinate 7. 0.15 g (0.60 mmol) of
3 were used to give an intensely orange solid (0.12 g, 98%), mp >
300 °C (from EtOH) Found: C, 45.28; H, 4.87; N, 31.07%. Calcd
for C10H8N6•3H2O: C, 45.11; H, 5.30; N, 31.56%; UV
λ
max(CH2Cl2)/nm 469.0;
λmax(MeCN)/nm 338.7 and 221.1;
λmax(MeOH)/nm 397.5 and 224.9; IR 3320, 1623, 1538, 1493,

2384 Bull. Chem. Soc. Jpn., 74, No. 12 (2001)
1434, 1299, 877, 656, and 630 cm−1 1H NMR (300 MHz,
π-Interactions of Modified Nucleobases
;
Shatkin, and S. Ochoa, Proc. Natl. Acad. Sci., U.S.A., 73, 1559
DMSO-d6; Me4Si) δ 6.02 (2H, s), 8.03 (1H, s), 8.34 (2H, t, J = 7.2
Hz), 8.73 (1H, dd, J = 7.2 and 6.9 Hz), 10.47 (2H, dd, J = 6.9 and
1.2 Hz).
2-Amino-6-(4-dimethylaminopyridinio)purinate 8. 0.15 g
(0.51 mmol) of cation 3 were given on the resin to give a lemon-
yellow solid (0.12 g, 98%) Found: C, 50.92; H, 5.82; N, 34.16%.
Calcd for C12H13N7•1.5H2O: C, 51.06; H, 5.71; N, 34.73%; UV
(1976).
8
T. Ishida, M. Katsuta, M. Inoue, Y. Yamagata, and T.
Ken-ichi, Biochem. Biophys. Res. Commun., 115, 849 (1983).
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10 C. A. Hunter, Chem. Soc. Rev., 1994, 101.
11 P. D. Lawley and P. Brookes, Nature, 192, 1081 (1961).
12 R. F. Newbold, W. Warren, A. S. C. Medcalf, and J. Amos,
Nature, 283, 596 (1980).
λ
max(CH2Cl2)/nm 385.8 and 300.8; λmax(MeCN)/nm 352.9, 305.1,
and 219.9; λmax(MeOH)/nm 353.4, 307.4, and 220.7; IR 3313,
3178, 1658, 1583, 1536, 1490, 1398, 1304, 1217, and 1157 cm−1
;
13 S. Metzger and B. Lippert, Angew. Chem., 108, 1321
(1996); Angew. Chem. Int. Ed. Engl., 35, 1228 (1996).
14 A. Schmidt, M. K. Kindermann, P. Vainiotalo, and M.
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15 A. Schmidt and M. Nieger, J. Chem. Soc., Perkin Trans 1,
1999, 1325; M. Mäkinen, A. Schmidt, P. Vainiotalo, Eur. J. Mass
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Lett., 1991, 4473.
1H NMR (300 MHz, DMSO-d6; Me4Si) δ 3.32 (6H, s), 5.90 (2H,
s), 7.29 (2H, d, J = 8.2 Hz), 7.89 (1H, s), 9.77 (2H, d, J = 8.2
Hz); MS m/z (FAB, mNBA) 257.3 (M++2, 91) and 40.1 (100).
2-Chloro-6-(1-pyridinio)purinate 9. 0.15 g (0.55 mmol) of
cation 5 were used to give a yellow solid (0.12 g, 95%), mp > 300
°C (from EtOH) Found C, 39.94; H, 4.65; N, 22.89%. Calcd for
C10H6ClN5: C, 39.54; H, 4.65; N, 23.05%; UV λmax(MeCN)/nm
374.2; IR 1605, 1526, 1479, 1376, 1306, and 1183 cm−1; 1H NMR
(300 MHz, DMSO-d6; Me4Si) δ 8.38 (2H, m), 8.42 (1H, s), 8.82
(1H, tt, J = 7.8 Hz), 10.43 (2H, m); 13C NMR (75 MHz, DMSO-
d6; Me4Si) δ 125.64, 127.80, 140.95, 142.43, 146.26, 148.24,
163.05, and 170.85; MS m/z (FAB, mNBA) 232.4.
2-Chloro-6-(4-dimethylpyridinio)purinate 10. 0.15 g (0.50
mmol) of the cation 6 were given on the resin to give a yellow sol-
id (0.12 g, 95%), mp > 300 °C (from water). Found: C, 36.51; H,
4.36; N, 18.79%. Calcd for C12H11ClN6•6.5H2O: C, 36.78; H,
6.17; N, 21.44%; UV λmax(MeCN)/nm 344.1, 287.3, and 257.4; IR
1654, 1585, 1527, 1445, 1388, 1295, 1228, 1181, 1142, and 987
cm−1; 1H NMR (300 MHz, DMSO-d6; Me4Si) δ 7.29 (2H, d, J =
8.4 Hz), 8.23 (1H, s), 9.73 (2H, d, J = 8.4 Hz); MS m/z (FAB,
mNBA) 275.6.
16 P. A. Searle and T. F. Molinski, J. Org. Chem., 60, 4296
(1995).
17 For an alternative synthesis of 3 and 7, see: B. Skalski, S.
Paszyk, R. Adamiak, R. P. Steer, and R. E. Verrall, Can. J. Chem.,
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18 W. D. Ollis, S. P. Stanforth, and C. A. Ramsden, Tetrahe-
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20 J. M. Jallon, Y. Risler, C. Schneider, and J. M. Thierry,
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The Deutsche Forschungsgemeinschaft DFG and the Fonds
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nancial support.
21 B. Pullman and A. Pullman, Proc. Natl. Acad. Sci. U.S.A.,
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22 PM3-calculations23 were carried out using MOPAC 6.024
on a Convex 3440. The structures were first optimized with the
default gradient requirements and subsequently refined with the
options EF DMAX = 0.05, GNORM = 0.01, SCFCRT = 1 ×
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