Synthesis and structure of the first ribbed-functionalized quinoxaline clathrochelate: Design of cage complexes for efficient intercalation into DNA structure

Article abstract of DOI:10.1023/B:RUCB.0000042276.31796.ca

Condensation of the dichloride clathrochelate FeBd₂(Cl ₂Gm)(BF)₂ precursor (Bd^2- is the α-benzyl dioxime dianion, Gm is the glyoxime residue) with quinoxaline-2,3-dithiol in the presence of triethylamine afforded the ribbed-functionalized quinoxaline clathrochelate. The structure of this complex was established by X-ray diffraction analysis.

Full text of DOI:10.1023/B:RUCB.0000042276.31796.ca

1218
Russian Chemical Bulletin, International Edition, Vol. 53, No. 6, pp. 1218—1222, June, 2004
Synthesis and structure of the first ribbedꢀfunctionalized
quinoxaline clathrochelate: design of cage complexes for
efficient intercalation into DNA structure ✾
b
b
c
a
Ya. Z. Voloshin,a,b A. S. Belov, A. Yu. Lebedev, O. A. Varzatskii, M. Yu. Antipin,
ꢀ
Z. A. Starikova,a and T. E. Kronb
aA. N. Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences,
28 ul. Vavilova, 119991 Moscow, Russian Federation.
Fax: +7 (095) 135 5085. Eꢀmail: star@xray.ineos.ac.ru
bL. Ya. Karpov Institute of Physical Chemistry,
10 ul. Vorontsovo Pole, 105064 Moscow, Russian Federation.
Fax: +7 (095) 975 2450. Eꢀmail: voloshin@cc.nifhi.ac.ru
cV. I. Vernadskii Institute of General and Inorganic Chemistry, National Academy of Sciences of Ukraine,
32/34 ul. Palladina, 03680 Kiev, Ukraine.
Fax: +38 (044) 424 3070. Eꢀmail: varzatsky@ionc.kar.net
Condensation of the dichloride clathrochelate FeBd2(Cl2Gm)(BF)2 precursor (Bd2– is the
αꢀbenzyl dioxime dianion, Gm is the glyoxime residue) with quinoxalineꢀ2,3ꢀdithiol in the
presence of triethylamine afforded the ribbedꢀfunctionalized quinoxaline clathrochelate. The
structure of this complex was established by Xꢀray diffraction analysis.
Key words: macrocyclic compounds, clathrochelates, iron(II), Xꢀray diffraction analysis.
A recent keen interest in trisꢀαꢀdiazine complexes of
Results and Discussion
rareꢀearth elements and ruthenium(II), iridium, and
rhodium(III) ions, is associated mainly with the fact that
these complexes show promise in biochemistry as lumiꢀ
nescent probes and reagents for DNA sequencing.1—3
In most cases, one of the three αꢀdiazine ligands, which
are prone to form nonbonded interactions with nucleic
bases, including πꢀstacking interactions, is used for effiꢀ
cient intercalation into DNA structure. The quinoxaline
system is one of the most efficient fragments of this type.
Earlier, it has been proposed to use polyaromatic subꢀ
stituents in apical fragments for modifications of cage
complexes with the aim of achieving efficient intercalaꢀ
tion into DNA structure.4,5 However, we have demonꢀ
strated6,7 that the mutual influence of apical substituꢀ
ents and the encapsulated metal ion is insignificant,
whereas substituents in ribbed fragments have a much
more substantial effect on the electronic properties and
geometry of the cage framework (and, therefore, of the
encapsulated metal ion) through a system of conjugated π
bonds of the chelate ring.8—13 We performed funcꢀ
tionalization of one of the three ribbed fragments of the
iron(II) cage complex for efficient intercalation into DNA
structure.
The quinoxalineꢀcontaining clathrochelate was synꢀ
thesized by the nucleophilic substitution of the reactive
chlorine atoms in one of the ribbed fragments with the
corresponding dithiolate dianion (Scheme 1).
The molecular structure of complex 4 is shown in
Fig. 1. The symmetry of the clathrochelate framework is
nearly D3h. In addition to the threefold symmetry pseudoꢀ
axis coinciding with the B(1)...B(2) axis, complex 4 has a
symmetry pseudoplane, which is perpendicular to the
B(1)...B(2) axis and passes through the midpoints of the
C—C bonds in the chelate rings and the encapsulated
iron(II) ion. The symmetry of the macrobicyclic frameꢀ
work deviates from D3h because the coordination polyꢀ
hedron of the iron(II) ion is intermediate between the
trigonal prism (TP, the distortion angle ϕ = 0°) and the
trigonal antiprism (TAP, ϕ = 60°). The N—Fe—N bond
angles in the chelate rings are substantially smaller than
the value characteristic of the ideal octahedron (90°);
these angles are in the range of 77.9—78.3° for the nitroꢀ
gen atoms of one chelate ring and in the range of
86.1—86.8° for the nitrogen atoms of the different diꢀ
oximate fragments. The N—Fe—N angles between the
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 6, pp. 1171—1174, June, 2004.
1066ꢀ5285/04/5306ꢀ1218 © 2004 Plenum Publishing Corporation

Ribbedꢀfunctionalized quinoxaline cathrochelate
Russ.Chem.Bull., Int.Ed., Vol. 53, No. 6, June, 2004
1219
Scheme 1
nitrogen atoms in the trans positions (150.5—151.8°) also
differ substantially from the ideal value (180°). The disꢀ
tortion angle ϕ of the coordination polyhedron intermeꢀ
diate between TP and TAP is 23.6°. The Fe(1)...B(1) and
Fe(1)...B(2) distances have equal values (2.966(3) Å). The
B(1)...Fe(1)...B(2) angle is 179.8°.
ing folding along the S(1)...S(2) and C(8)...C(13) lines
are 15.6 and 7.6°, respectively. In quinoxalineꢀcontaining
structures 5 and 6, the dihedral angles characterizing foldꢀ
ing along the S...S line are substantially larger (47.8 and
37.6°, respectively), whereas the remaining moiety of the
molecule is planar.14
In all three chelate fragments, the average Fe—N,
N—O, C=N, and C—C bond lengths are 1.912, 1.369,
1.305, and 1.449 Å, respectively. The bond angles in these
fragments are also virtually identical.
The tricyclic 1,4ꢀdithiinoꢀ2,3ꢀquinoxaline system in
molecule 4 is nonplanar. The dihedral angles characterizꢀ
F(2)
C(36)
C(37)
B(2)
O(6)
O(2)
C(24)
S(2)
C(25)
C(26)
O(4)
N(8)
C(12)
N(2)
N(6)
N(4)
C(23)
C(13)
C(8)
C(14)
C(7)
C(2)
C(6)
C(21)
C(11)
C(10)
C(22)
C(4)
C(3)
Fe(1)
C(5)
C(32)
C(31)
C(15)
N(5)
C(1)
N(1)
O(1)
C(9)
N(3)
N(7)
O(5)
B(1)
S(1)
C(16)
C(30)
C(20)
O(3)
C(17)
C(19)
C(18)
F(1)
Fig. 1. Molecular structure of clathrochelate 4.

1220
Russ.Chem.Bull., Int.Ed., Vol. 53, No. 6, June, 2004
Voloshin et al.
However, in the complex of 5 with tetracyanoquinoꢀ
dimethane, this angle is 1.7 and 10.0° in two independent
molecules 5. One of molecules 5 is involved in stronger
intermolecular stacking interactions with the tetracyanoꢀ
quinodimethane molecules compared to another molꢀ
ecule 5. Therefore, the deviation of this system from plaꢀ
narity reflects the character of intermolecular interacꢀ
tions in the crystal structure and is not characteristic of
the tricyclic fragment as such.
It should also be noted that the C—S bond lengths
in molecule 4 (1.723—1.738 Å) are, on the average,
smaller than those in molecules 5 and 6 (1.75—1.76 Å).
The nitrogen atoms in the quinoxaline fragment of the
clathrochelate molecule are substantially nonequivalent;
the N(7)—C(8) bond length (1.414(3) Å) is larger than
the N(8)—C(13) bond length (1.396(3) Å). The
C(7)—N(7)—C(8) bond angle (117.1(4)°) is smaller than
the C(13)—N(8)—C(14) bond angle (120.8(4)°). This may
be associated with vibrations of the C(8)—C(13) benzene
ring, as evidenced by the larger thermal parameters of the
N(7), N(8), and C(8)—C(13) atoms compared to other
atoms.
dihedral angle between the planes of the benzene ring
and the N(7)—N(8)—C(7)—C(8)—C(13)—C(14) ring
is 80.2°). The angle between the C(1s)...C(4s) line of the
benzene ring and the N(7)...N(8) line is 21.6°. One of the
hydrogen atoms of the benzene ring forms a contact with
the N(8) atom, whose length (2.58 Å) corresponds to the
sum of the van der Waals radii.15
The parameters of the 57Fe Mössbauer spectrum
of quinoxaline clathrochelate 4 (the isomer shift is
0.33 mm s–1, the quadrupole splitting is 0.47 mm s–1
)
are characteristic of lowꢀspin iron(II) complexes with
a geometry intermediate between TP and TAP, which
is consistent with the aboveꢀgiven Xꢀray diffraction
data. It should be noted that, in spite of the nonꢀ
equivalence of the dioximate fragments of the molecule,
the UVꢀVis spectrum of complex 4 shows only one inꢀ
tense Fed → Lπ* chargeꢀtransfer band in visible region,
which is indicative of strong conjugation in the clathroꢀ
chelate moiety.
Experimental
In the crystal, the adjacent molecules are linked in
pairs by the intermolecular S(2)...F(2) contacts (3.24 Å),
whose length is close to the sum of the van der Waals radii
(3.21 Å).15 Nevertheless, the "dimers" formed due to these
interactions are clearly seen in the crystal of 4 (Fig. 2). In
addition, two benzene solvate molecules are also involved
in these "dimers". The planes of these benzene molecules
are virtually orthogonal to the quinoxaline fragment (the
The chemical reagents and the physical methods (used in
the present study) were described in detail earlier.13 The
FeBd2(Cl2Gm)(BF)2 complex (Bd2– is the αꢀbenzyl dioxime
dianion, Gm is the glyoxime residue) was prepared according to
a procedure described earlier.10 2,3ꢀDichloroquinoxaline (1) was
synthesized according to a known procedure.16
2,3ꢀDiisothiuronium quinoxaline dihydrochloride (2). A mixꢀ
ture of 2,3ꢀdichloroquinoxaline (1) (10.3 g, 52 mmol) and thioꢀ
urea (8.7 g, 115 mmol) was dissolved/suspended in 95% EtOH
(120 mL). The reaction mixture was refluxed for 5 h. The goldishꢀ
orange precipitate that formed was filtered off, washed with
EtOH (10 mL), and dried. The yield was 11.1 g (61%). 1H NMR
(DMSOꢀd6), δ: 7.48, 7.57, and 7.72 (all m, 4 H, Ar); 9.85 and
10.00 (both br.s, 6 H, NH). 13C{1H} NMR (DMSOꢀd6), δ:
116.5, 126.5, 127.8, 131.0, 131.1, and 134.7 (all Ar); 159.8 and
164.6 (both C=CS); 170.6 (S—C=N).
Quinoxalineꢀ2,3ꢀdithiol (3). A mixture of diisothiuronium
dihydrochloride 2 (11.1 g, 40 mmol) was dissolved/suspended
in water (40 mL) and a solution of KOH (4.9 g, 90 mmol)
in water (20 mL) was added. The orange precipitate that
formed was filtered off, washed with water, and suspended
in water (5 mL). A saturated aqueous KOH solution was
added portionwise to pH ≈ 14 and until the precipitate was
completely dissolved. A 1 M HCl aqueous solution was added
with stirring to the darkꢀbrown solution to pH ≈ 1. The darkꢀ
brown precipitate that formed was filtered off, washed with waꢀ
ter, and dried in vacuo. The yield was 6.6 g (85%). 1H NMR
(DMSOꢀd6), δ: 7.27 and 7.40 (both s, 4 H, Ar); 14.2 (s, 2 H,
SH). 13C{1H} NMR (DMSOꢀd6), δ: 115.5, 125.6, 127.8 (Ar);
179.3 (S—C=N).
F(2)
S(2A)
B(2)
Fe(1)
B(1)
F(1)
S(2)
S(1)
F(2A)
C(14)
N(8)
C(13)
C(7)
N(7)
C(8)
1,20ꢀDifluoroꢀ23,24,29,30ꢀtetraphenylꢀ2,19,21,26,27,32ꢀ
hexaoxaꢀ5,16ꢀdithiaꢀ3,7,14,18,22,25,28,31ꢀoctaazaꢀ1,20ꢀ
diborapentacyclo[18.6.6.04,17.06,15.08,13]dotriacontaꢀ
3,6,8(13),9,11,14,17,22,24,28,30ꢀundecaene(2–)iron(2+) (4).
A solution of the clathrochelate FeBd2(Cl2Gm)(BF)2 preꢀ
Fig. 2. Formation of "dimers" in the crystal of 4•1.5C6H6.

Ribbedꢀfunctionalized quinoxaline cathrochelate
Russ.Chem.Bull., Int.Ed., Vol. 53, No. 6, June, 2004
1221
cursor (0.75 g, 1 mmol) in CH2Cl2 (30 mL) and a solution
of quinoxalineꢀ2,3ꢀdithiol (3) (0.18 g, 1.1 mmol) and Et3N
(0.3 mL, 2.2 mmol) in a 3 : 2 1,4ꢀdioxane—DMF mixture
(50 mL) were added dropwise with vigorous stirring at an
equivalent rate to CH2Cl2 (100 mL) at ~20 °C for 3 h. The
reaction mixture was stirred at ~20 °C for 30 h. Then a soluꢀ
tion of quinoxalineꢀ2,3ꢀdithiol (3) (0.09 g, 0.55 mmol) and
Et3N (0.15 mL, 1.1 mmol) in a 3 : 2 1,4ꢀdioxane—DMF mixꢀ
ture (60 mL) was added dropwise and the reaction mixture
was stirred at 50 °C for 4 h. The precipitate that formed
was filtered off and the filtrate was washed successively with
water (2×100 mL), a saturated citric acid aqueous solution
(2×50 mL), a saturated aqueous Na2CO3 solution (2×50 mL),
and water (2×100 mL). The organic phase was dried with MgSO4
and then concentrated to dryness in vacuo. The solid residue was
washed with hexane, dissolved in CH2Cl2, and separated by
chromatography on SPHꢀ300 silica gel (Chemapol) (CH2Cl2
as the eluent), two main fraction being collected. Based on
All calculations were carried out using the
SHELXTL PLUS 5 program package.18 The atomic coordinates
were deposited with the Cambridge Structural Database.
This study was financially supported by the Russian
Foundation for Basic Research (Project No. 03ꢀ03ꢀ32531)
and the Grant from the President of the Russian Federaꢀ
tion (the Federal Program for the Support of Leading
Scientific Schools, Grant NShꢀ1060.2003.03).
References
1. K. E. Erkkila, D. T. Odom, and J. K. Barton, Chem. Rev.,
1999, 99, 2777; I. V. Yang and H. H. Thorp, Inorg. Chem.,
2000, 39, 4969; E. D. A. Stemp and J. K. Barton, Inorg.
Chem., 2000, 39, 3868; S. I. Khan, A. E. Beilstein, M. Sykora,
G. D. Smith, X. Hu, and M. W. Grinstaff, Inorg. Chem.,
1999, 38, 3922; D. Z. M. Coggan, I. S. Haworth, P. J.
Bates, A. Robinson, and A. Rodger, Inorg. Chem., 1999,
38, 4486.
2. V. Balzani, A. Juris, M. Ventury, S. Campagha, and
S. Serroni, Chem.Rev., 1996, 96, 759; R. H. Terbrueggen,
T. W. Johann, and J. K. Barton, Inorg. Chem., 1998,
37, 6874.a
3. M. D. Ward and F. Barigelletti, Coord. Chem. Rev., 2001,
216—217, 127; C. Stinner, M. D. Wightman, S. O. Kelley,
M. G. Hill, and J. K. Barton, Inorg. Chem., 2001, 40, 5245;
W. J. Mei, J. Liu, K. C. Zheng, L. J. Lin, H. Chao, A. X. Li,
F. C. Yun, and L. N. Ji, Dalton Trans., 2003, 1352; H. Xu,
K. C. Zheng, Y. Chen, Y. Z. Li, L. J. Lin, H. Li, P. X.
Zhang, and L. N. Ji, Dalton Trans., 2003, 2260; J.ꢀK. Lee,
S.ꢀH. Lee, M. Kim, H. Kim, D.ꢀH. Kim, and W.ꢀY. Lee,
Chem. Commun., 2003, 1602; A. Kapturkiewicz and
G. Angulo, Dalton Trans., 2003, 3907; J. Slinker,
D. Bernards, P. L. Houston, H. D. Arbuca, S. Bernhard,
and G. G. Malliaras, Chem. Commun., 2003, 2392; R. Wilson
and M. K. Johansson, Chem. Commun., 2003, 2710;
C. Metcalfe, I. Haq, and J. A. Thomas, Inorg. Chem., 2004,
43, 317; J. D. Tibodeau and H. H. Thorp, Inorg. Chem.,
2004, 43, 408.
1
the H and 13C{1H} NMR spectroscopic data, the more mobile
yellowꢀorange fraction was identified as the starting dichloꢀ
rideFeBd2(Cl2Gm)(BF)2 complex , whereas the less mobile red
fraction was characterized as the target quinoxaline clathroꢀ
chelate 4. The yield of 4 was 0.25 g (29%). Found (%): C, 52.59;
H, 2.86; N, 12.87; Fe, 6.35. C38H24N8O6B2S2F2Fe. Calcuꢀ
lated (%): C, 52.56; H, 2.77; N, 12.91; Fe, 6.43. MS,
m/z 868 [M]+•
.
1H NMR (CD2Cl2), δ: 7.27 (br.s, 20 H, Ph);
7.68 and 7.85 (both m, 2 H each, Ar). 13C NMR {1H} (CD2Cl2),
δ: 128.3, 129.2, 130.6, and 130.8 (all Ph); 131.7, 140.1, and
140.6 (all Ar); 144.9 (S—C=N); 157.3 (Ph—C=N). IR (KBr),
ν/cm–1: 1544 (S—C=N); 1578 (Ph—C=N); 922, 1066, 1083
(N—O); 1217 (m, ν(B—O) + ν(B—F)). UVꢀVis spectrum
(CH2Cl2): λmax/nm (ε•10–3/L mol–1 cm–1): 270 (19), 292 (15),
338 (45), 403 (4.9), 484 (25).
Xꢀray diffraction study. Red plateletꢀlike crystals of
4•1.5 C6H6 suitable for Xꢀray diffraction study were grown by
by slow evaporation of a saturated solution of this clathrochelate
in a 3 : 1 benzene—isooctane mixture. For the crystals of this
solvate: C47H33B2F2FeN8O6S2, M = 985.40, triclinic system,
at 120 K a = 10.337(2) Å, b = 13.277(2) Å, c = 16.343(3) Å,
α = 95.087(4)°, β = 90.218(4)°,
γ = 105.052(4)°, V =
2156.6(6) Å3, space group P–1, Z = 2, dcalc = 1.517 g cm–3. A total
of 24067 reflections were measured on a Bruker AXS SMART
1000 diffractometer equipped with a CCD detector at 120 K
(λꢀMoꢀKα, graphite monochromator, 2θmax = 58.14°) from
a single crystal of dimensions 0.2×0.4×0.6 mm3. Merging
of equivalent reflections gave 11338 independent reflections
(Rint = 0.0393), which were used for the structure solution and
refinement. The absorption correction (µ = 5.18 mm–1) was apꢀ
plied using the SADABS program17 (Tmax and Tmin are 0.862
and 0.518, respectively). The structure was solved by direct methꢀ
ods. All nonhydrogen atoms were located from difference elecꢀ
4. Y. Z. Voloshin, N. A. Kostromina, and R. Krämer, Clathroꢀ
chelates: Synthesis, Structure and Properties, Elsevier,
Amsterdam, 2002.
5. A. M. Sargeson, Coord. Chem. Rev., 1996, 151, 89.
6. Y. Z. Voloshin, O. A. Varzatskii, A. I. Stash, V. K. Belsky,
Y. N. Bubnov, I. I. Vorontsov, K. A. Potekhin, M. Y. Antipin,
and E. V. Polshin, Polyhedron, 2001, 20, 2721.
7. Ya. Z. Voloshin, O. A. Varzatskii, I. I. Vorontsov, M. Yu.
Antipin, A. Yu. Lebedev, A. S. Belov, and A. V. Pal´chik,
Izv. Akad. Nauk, Ser. Khim., 2003, 52, 1469 [Russ. Chem.
Bull., Int. Ed., 2003, 52, 1552].
tron density syntheses and refined anisotropically against F 2
.
hkl
All hydrogen atoms were placed in geometrically calculated poꢀ
sitions and refined using the riding model with U(H) = 1.2 U(C),
where U(C) are the equivalent thermal parameters of the carbon
atoms to which the corresponding H atoms are bound. The final
reliability factors are R1 = 0.0621 (calculated based on Fhkl for
7221 reflections with I > 2σ(I )), wR2 = 0.1430 (calculated based
8. Y. Z. Voloshin, O. A. Varzatskii, A. V. Palchik, A. I. Stash,
and V. K. Belsky, New J. Chem., 1999, 23, 355.
9. Y. Z. Voloshin, O. A. Varzatskii, T. E. Kron, V. K. Belsky,
V. E. Zavodnik, and A. V. Palchik, Inorg. Chem., 2000,
39, 1907.
10. Y. Z. Voloshin, V. E. Zavodnik, O. A. Varzatskii, V. K.
Belsky, A. V. Palchik, N. G. Strizhakova, I. I. Vorontsov,
and M. Y. Antipin, Dalton Trans., 2002, 1193.
on F 2 for all 4295 reflections), GOOF = 1.093, 613 paramꢀ
hkl
eters were refined.

1222
Russ.Chem.Bull., Int.Ed., Vol. 53, No. 6, June, 2004
Voloshin et al.
11. Y. Z. Voloshin, O. A. Varzatskii, T. E. Kron, V. K. Belsky,
V. E. Zavodnik, N. G. Strizhakova, V. A. Nadtochenko, and
V. A. Smirnov, Dalton Trans., 2002, 1203.
12. Y. Z. Voloshin, O. A. Varzatskii, A. V. Palchik, N. G.
Strizhakova, I. I. Vorontsov, M. Y. Antipin, D. I. Kochubey,
and B. N. Novgorodov, New J. Chem., 2003, 27, 1148.
13. Ya. Z. Voloshin, O. A. Varzatskii, I. I. Vorontsov, M. Yu.
Antipin, A. Yu. Lebedev, A. S. Belov, and N. G. Strizhakova,
Izv. Akad. Nauk, Ser. Khim., 2004, 53, 92 [Russ. Chem. Bull.,
Int. Ed., 2004, 53, 92].
15. Yu. V. Zefirov and P. M. Zorkii, Usp. Khim., 1995, 64, 446
[Russ. Chem. Rev., 1995, 64 (Engl. Transl.)].
16. Sintezy geterotsiklicheskikh soedinenii [Syntheses of Orꢀ
ganic Compounds], Izdꢀvo AN Arm. SSR, Vol. 9, 1972 (in
Russian).a
17. G. M. Sheldrick, SADABS: A Program for Exploiting the
Redundancy of AreaꢀDetector XꢀRay Data, University of
Göttingen, Göttingen, Germany, 1999.
18. G. M. Sheldrick, SHELXTL v. 5.10, Structure Determination
Software Suite, Bruker AXS, Madison, Winsconsim,
USA, 1998.
14. P. J. Skabara, R. Berridge, K. Prescott, L. M. Goldenberg,
E. Orti, R. Viruela, R. PouꢀAmerigo, A. S. Batsanov, J. A.
K. Howard, S. J. Coles, and M. B. Hursthouse, J. Mater.
Chem., 2000, 10, 2448.
Received April 26, 2004