Sodium cation complexation in a macrocycle containing thymines as sidearm donor groups

Article abstract of DOI:10.1023/A:1009534904760

Previous studies of macrocycles having alkyl sidearms terminated in adenine or thymine have been focused on intermolecular association. Electrospray mass spectrometric analyses suggested that sodium complexation could be a major alternative process in the presence of the appropriate cation. Sodium cation complexation by N,N′-bis(3-(1-thyminyl)propyl)-4,13-diaza-18-crown-6 has been confirmed by X-ray crystallographic analysis. A sodium cation is bound in the center of the macroring. The four ether oxygens and two thyminyl carbonyl donors have the shortest contacts with the two, macroring nitrogen atoms being somewhat more remote. Neither the iodide counterion nor an acetone of solvation appears to interact with the sodium cation. Crystal Data: Triclinic, P₁, a = 11.9371(12), b = 12.1588(13), c = 13.7885(14) A, α = 78.083(2)°, β = 83.213(2)°, γ = 78.997(2)°, and D_calc = 1.392 g cm^-3, Ζ= 2.

Full text of DOI:10.1023/A:1009534904760

Journal of Chemical Crystallography, Vol. 30, No. 4, 2000
Sodium cation complexation in a macrocycle containing
thymines as sidearm donor groups
(
1)
(2)
(1)
(1)
�
Stephen L. De Wall, Leonard J. Barbour, Otto F. Schall, and George W. Gokel
Received January 11, 2000; revised August 25, 2000
Previous studies of macrocycles having alkyl sidearms terminated in adenine or thymine have
been focused on intermolecular association. Electrospray mass spectrometric analyses sug-
gested that sodium complexation could be a major alternative process in the presence of
0
the appropriate cation. Sodium cation complexation by N,N -bis(3-(1-thyminyl)propyl)-4,13-
diaza-18-crown-6 has been confirmed by X-ray crystallographic analysis. A sodium cation is
boundinthecenterofthemacroring. Thefouretheroxygensandtwothyminylcarbonyldonors
have the shortest contacts with the two, macroring nitrogen atoms being somewhat more re-
mote. Neither the iodide counterion nor an acetone of solvation appears to interact with the
sodium cation. Crystal Data: Triclinic, P
A, � = 78.083(2) , � = 83.213(2) , � = 78.997(2) , and Dcalc = 1.392 g cm , Z = 2.
¯
, a = 11.9371(12), b = 12.1588(13), c = 13.7885(14)
1
˚
�
�
� � 3
KEY WORDS: Alkyl sidearms; adenine; thymine.
Introduction
spectrometric analysis were prominent but even such
less often used techniques as vapor pressure osmom-
Deoxyribonucleic acids are the essential genetic
etry were applied. One method that was lacking in
these studies was X-ray crystallographic analysis be-
cause crystals of suitable quality and applicability
failed to form. We now report the structure of a
dithymidinyl complex in which the anticipated com-
plexation mode is demonstrated.
material for prokaryotes and eukaryotes alike. Much
is known about the structures of these heterocyclic
bases and remarkable work has been reported re-
cently that permits modification and a better un-
derstanding of its interactions. The number of such
1
small molecule models for DNA is modest, however.
Detailed studies of selective or specific hydrogen
bonding and �-stacking interactions are certainly fa-
cilitated by the less complex structures inherent in
Experimental section
2
Crystallization of 1�NaI�Me2CO
artificial receptor molecules. Several excellent ef-
3
forts have been reported in this arena by Sessler,
4
5
Compound 1 and an equivalent amount of NaI
were dissolved in warm acetone. Crystals of the com-
plex were grown by slow evaporation of the solvent
over several weeks. Crystals suitable for X-ray analy-
sis were obtained as colorless rhombohedroids.
Kanematsu, and others. We have also reported vari-
ous model systems that were developed to assist in the
general problem of understanding these interactions.6
Evidence for interactions was gained by a variety of
analytical techniques. Among them, NMR and mass
(
1)
Bioorganic Chemistry Program & Dept. of Molecular Biology &
Pharmacology, Washington University School of Medicine 660 S.
Euclid Ave., Campus Box 8103, St. Louis, Missouri 63110.
Dept. of Chemistry, University of Missouri, 601 S. College Ave.,
Columbia, Missouri 65211.
X-ray crystallography
Intensity data for 1�NaI�Me2CO were collected
(
2)
at 173(1) K on a Bruker SMART CCD diffractome-
�
˚
To whom correspondence should be addressed.
ter (ω scan mode Mo-K� radiation, � = 0.7107 A).
2
27
1
074-1542/00/0400-0227$18.00/0 �C 2000 Plenum Publishing Corporation

228
De Wall, Barbour, Schall, and Gokel
Table 1. Crystal Data and Structure Refinement
0
Compound
N,N -bis(3-(1-thyminylpropyl))-4,13-diaza-18-crown-6
CCDC no.
CCDC-1003/5864
Color/shape
Crystal size
Colorless/rhombohedroid
3
0.40 � 0.35 � 0.15 mm
Empirical formula
Formula weight
Temperature
Crystal system
Space group
C31H52IN6NaO9
802.68
173(2) K
Triclinic
P � 1
˚
0.71070 A
Wavelength
Unit cell dimensions
˚
˚
˚
�
�
a = 11.9371(12) A � = 78.083(2)
b = 12.1588(13) A � = 83.213(2)
c = 13.7885(14) A � = 78.997(2)�
˚
3
Volume
1915.7(3) A
Z
2
3
Density (calculated)
Absorption coefficient
Diffractometer/scan
1.392 Mg/m
0.903 mm
Bruker SMART/CCD area detector
1.51 to 27.16
�
1
�
range for data collection, deg
�
Data were corrected for absorption using the program
SADABS. Structure solution was done by direct
crystals (mp 129–130 C). Approximately 40% of the
7
isolatedproductwasthesingle-armedthyminylpropyl
crown. In previous studies, we have abbreviated 1
as T-O-T and the single-armed macrocycle as T-O
(Scheme 1).
We had reason to believe that T-O-T would form
an alkali metal cation complex using the sidearms
as donor groups. Electrospray ionization (ESI) mass
spectral analyses had previously been conducted on
T-O-T and the bis(adenyl) analog, A-O-A.16 The ESI
spectra were acquired on a triple quadrupole tandem
mass spectrometer equipped with an electrospray
methods and structure refinement was accomplished
8
9
with SHELX-97 software using the X-Seed inter-
face. Direct methods yielded all non-hydrogen atoms
of the asymmetric unit. These atoms were refined
anisotropically (full-matrix least-squares method on
2
F ). Hydrogen atoms were placed in calculated po-
sitions with their isotropic thermal parameters rid-
ing on those of their parent atoms (Table 1). All X-
ray structure figures were prepared with X-Seed and
POV-Ray.10
Results and discussion
Our efforts to probe interactions involving var-
11
ious residues using bibracchial lariat ethers dates
12
back more than a decade, especially our endeavors
to identify cation-� interactions.13 Indeed, our origi-
nal effort to construct a molecular box using H-bond
interactions of nucleobases began about 1985.14 The
latter work was more fruitful than the cation-� stud-
ies, which have only recently proved successful.15
We prepared the bibracchial lariat ether re-
quired for this study as previously described. First,
the carbonyl oxygens of thymine were protected as
trimethylsilyl enol ethers. Alkylation at nitrogen and
deprotection, afforded 1-(3-bromopropyl)thymine
�
(
62%, mp 137–139 C). Alkylation of diaza-18-crown-
6
with the bromide gave the crown having propy-
lenethyminyl sidearms, 1, (10–15%) as small white
Scheme 1

Sodium cation
229
Fig. 1. Structure of T-O-T�NaI shown in ball and stick and CPK representations.
interface.17 Solutions of T-O-T were prepared in 2:1
v/v) CHCl3:CH3OH at a concentration of 3.33 mM
each. Acetic acid was added in concentrations of
.5% and 5% (v/v) to two of the solutions and NaCl
heteroatoms and the carbonyl oxygens of the thymine
sidearms bind the Na cation. The sodium cation is
+
(
bound by six oxygen atoms. The contacts are sym-
+
1
metrical. The four ether Na -O contacts are 2.416(3)
˚
˚
˚
˚
(
0.33 mM) was added to the third solution. Proto-
A, 2.648(3) A, and 2.708(3) A, and 2.713(3) A. The
+
+
nated T-O-T, i.e., [T-O-T�H] (m/z = 595) was the
base peak in the spectrum when a 1:1 mixture of A-
O-A and T-O-T were sprayed in the presence of ei-
carbonyl donors (actually amides) form closer Na
˚
==
+
�
contacts (2.488, 2.468 A) and the C O ���Na an-
gles in the two complexes are 151.14 and 154.19 . The
+
----
+
˚
ther 1.5% or 5% HOAc. Likewise, [T-O-T�Na] was
macroring nitrogen Na distances are 3.088 A and
3.201 A. It is interesting to note that the four ether-
˚
the base peak in the presence of NaCl. In the lat-
ter case, we hypothesized that a ring-bound cation
was further stabilized by a carbonyl oxygen of the
thyminyl residue. Exactly these interactions are ap-
parent in solid state structure shown in Fig. 1.
to-sodium contacts are longer than are observed in
many crown complexes. This suggests that the car-
bonyl groups are providing strong solvation as ex-
+
pected for an amide donor group. The N
˚
tance near 3 A is typical of crown complexes and is
---- Na dis-
Compound 1 (T-O-T) was dissolved in acetone
in the presence of NaI. Slow evaporation afforded
nearly colorless crystals that had the stoichiometry
T-O-T�NaI�Me2CO. The asymmetric unit consists of
two half-crown ether molecules, each with its sodium
cation positioned on an inversion center, and one io-
dide ion. The solid state structure of one of the two
unique T-O-T�NaI complexes is shown in Fig. 1 as
ORTEP and space-filling structures. In the solid state
structure the thymine groups are clearly positioned
above and below the macroring, and the macrocycle’s
+
+
18
little different for Na or K complexes. Sodium is
octacoordinatedbutthedistancessuggestthatthema-
jor stabilization of the alkali metal cation is provided
by oxygen.
The asymmetric unit contains two crystallo-
graphically unique molecules of 1�NaI and a single
molecule of acetone. However, the two complexes
in the asymmetric unit are essentially identical in
conformation. The contents of the asymmetric unit
are shown in Fig. 2 in the tube and space-filling

230
De Wall, Barbour, Schall, and Gokel
Fig. 2. Structure of T-O-T�NaI showing both complexes and occluded acetone in ball and stick and CPK representations.
metaphor. A molecule of acetone is apparent be-
tween them and the iodide counterion is not shown.
The potentially powerful carbonyl donor group of
Conclusion
The solid state structure presented here confirms
˚
+
acetone is more than 5 A distant from the Na of one
the previously hypothesized carbonyl-to-sodium
cation interaction between a sidearm thyminyl donor
group and the ring bound cation. The carbonyl groups
afford closer contacts than do the macroring ether
donors suggesting a stronger interaction. The fully
charged iodide anion and an interstitial acetone
molecule, both potentially good donors for an alkali
metal ion, do not contact sodium.
˚
complex and more than 6 A away from the other. It
is clearly not serving as a donor group for the alkali
metal ion. Although iodide is not shown in Fig. 1,
˚
+
it is � 7.5 A from Na . This distance is far too short
for the interaction to be significant. Moreover, as
shown in the space-filling metaphor in Fig. 2, Na is
+
completely surrounded by the array of oxygen and
nitrogen donor groups. The remoteness of iodide
+
�
˚
(
lower right, K ↔I > 7 A) is apparent. Acetone’s
Acknowledgment
methyl groups are in the center of the figure and
the carbonyl group is pointing to the left and back.
The opposite, axial-like interactions of thymine are
apparent from the line these residues form from the
We are grateful to the NIH and NSF for support
of this work.
�
upper left descending at an approximate 60 angle.
It is worth noting that the acetone carbonyl group
is close to one of the thyminyl residues. In fact, ace-
tone’s oxygen is pointed toward one thyminyl imide
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