- Email: [email protected]
Stabilization of the non-canonical adenine–adeninium base pair by N(7) coordination of Zn(II)
JOURNAL OF
Inorganic Biochemistry Journal of Inorganic Biochemistry 99 (2005) 2226–2230 www.elsevier.com/locate/jinorgbio
Stabilization of the non-canonical adenine–adeninium base pair by N(7) coordination of Zn(II) Pilar Amo-Ochoa a, Simone S. Alexandre b, Ce´sar Pastor c, Fe´lix Zamora
d,*
a
c
Departamento de Tecnologı´a Industrial, Universidad Alfonso X ‘‘El Sabio’’, 28691 Villanueva de la Can˜ada, Madrid, Spain b Departamento de Fı´sica de la Materia Condensada, Universidad Auto´noma de Madrid, 28049 Madrid, Spain Servicio Interdepartamental de Apoyo a la Investigacio´n (rayos-X), Universidad Auto´noma de Madrid, 28049 Madrid, Spain d Departamento de Quı´mica Inorga´nica, Facultad de Ciencias, Universidad Auto´noma de Madrid, 28049 Madrid, Spain Received 24 May 2005; received in revised form 26 July 2005; accepted 27 July 2005 Available online 23 September 2005
Abstract A new zinc (II) compound with 9-ethyladenine (9-EtA) of formula [Zn(9-EtA–N7)Cl3](9-EtAH) has been synthesized and characterized by X-ray diffraction. Its X-structure consists of an Zn(II) anionic complex and 9-ethyladeninium as counteranion. The Zn(II) complex shows a distorted tetrahedral geometry in which three Cl and an 9-EtA coordinates through N(7) position are the ligands. An indirect chelation via intramolecular H-bond between N(6)H and an Cl ligand is present in the complex. The network of [Zn(9-EtA–N7)Cl3](9-EtAH) shows interesting features. Thus, self-association of coordinated adenine–adeninium takes place by H-bonding of N(6)–H N(1) and N(6)–H N(7), leading to a polymeric ribbon-like 1D supramolecular arrangement. Ab initio calculations have been applied in order to study the stability of the adenine–adeninium interaction due to the coordination of the Zn(II) to the N(7) position and to compare experimental and theoretical structural data. Ó 2005 Elsevier Inc. All rights reserved. Keywords: Zn(II)–nucleobases; Supramolecular assemblies; Crystal structure; Ab initio calculations
The interaction of metal ions with DNA and its constituents is of considerable interest due to the biological significance of theses studies. Zinc is considered as an essential biological element, presents in a number of proteins, including some interacting with DNA [1]. In addition, there are several biological processes in which direct interactions between zinc ions and nucleic acids are encountered. Zn(II) ions are involved in processes of DNA recognition, DNA hydrolysis, DNA B ! Z transitions, DNA unwinding and rewinding, among others [2–4]. The role of nucleobases in the recognition process has attracted attention since these molecules posses several functions which can be used to form hydrogen-bonding *
Corresponding author. Tel.: +34 914973962; fax: +34 914974833. E-mail address: [email protected] (F. Zamora).
0162-0134/$ - see front matter Ó 2005 Elsevier Inc. All rights reserved. doi:10.1016/j.jinorgbio.2005.07.015
or metal-binding. Nucleobases provide interesting building blocks for forming extended structures, not only by the multiple possibilities in which bases may interact by H-bonds, but also for the possible p-stacking between them [5]. Particularly, the well-known ability of adenine and guanine to form hydrogen bonds with other nucleobases can allow the formation of supramolecular structures with chemical and biological interest [6,7]. Coordination of metal ions to nucleobases can modify the usual H-bond interactions between bases, allowing new arrangements and stabilizing certain types of noncanonical base–base associations [8]. It has been observed that Zn(II)–nucleobase interactions are essential for the stabilization of non-canonical DNA structures such as triplexes and hairpins [9]. Zinc is also important for the stabilization of purine Æ purine–pyrimidine DNA triplexes [10]. Ab initio calculations have shown that
P. Amo-Ochoa et al. / Journal of Inorganic Biochemistry 99 (2005) 2226–2230
coordination of Zn(II) to N(7) of adenine causes stabilization of the non-canonical guanine–adenine base pairs [11]. It has been also proven by theoretical studies that, when guanine is metalated at N(7), several guanine– nucleobase pairs undergo stabilization without any major change in the geometry of the guanine [11,12]. However, the number reports on structural models of Zn(II) binding to nucleic acids is still scarce. As a continuation of our research project in the group-12 metal ion interactions with nucleobases [13–16], we now report on the synthesis of a new Zn(II)-9-ethyladenine compound, its structural study by X-ray diffraction, and ab initio calculations on the stabilization induced by the Zn(II) coordination to the base in the non-canonical A Æ AH+ base pair present in this compound. The reactions between ZnCl2 and 9-ethyladenine (9EtA), under several conditions and stoichiometries (see Sup. Mat.), do not allow us identifying any pure compound. However, in the reaction between [ZnCl2(6-MPH)2] Æ MeOH [17,18] and 9-EtA allows to characterize the new compound [Zn(9-EtA–N7)Cl3](9-EtAH) by substitution the 6-mercaptopurine (6-MPH) in the mentioned complex.1 Adenine has proved to be a very versatile ligand providing, at physiological pH, potential three binding sites (N1,N3,N7). The N(1) position is the preferred metal-binding site at neutral pH, while the N(7) position is the preferred one in strong acidic conditions, when N(1) is protonated [19]. These facts have specifically been observed for Zn(II)-adenine complexes, in which it has been described that coordination at N(7) takes place when the adenine is protonated (strong acid conditions, 2 M HCl) [20,21] while coordination at N(1) is observed under slight acid conditions [22]. A search in the Cambridge Crystallographic Data Centre [23], of Zn(II) complexes of adenine nucleobase, found 16 examples, being the coordination of Zn(II) to N(7) the most usual binding mode. However, in the complexes showing Zn(II) coordinated to N(7), the N(1) atom is protonated. Details of the data collection and refinement of [Zn(9EtA–N7)Cl3](9-EtAH) are given in Table 1. In Table 2, a selection of distances and angles are listed. The molecular structure consists on a distorted tetrahedral coordination geometry around the Zn(II) (Figure S1), with the metal to donor atom angles ranging between 106.5° and 116.2° (Table 2). Zn(II) coordinates to 9ethyladenine through N(7) and the remaining sites of the coordination sphere are completed with three chlorine ligands. The anionic complex shows as counterion an 9-ethyladeninium cation which presents the proton 1
9-EtA (0.068 g, 0.42 mmol) and [ZnCl 2 (6-MPH) 2 ] Æ MeOH (0.125 g, 0.28 mmol) were stirred in methanol (20 mL) at 70 °C for 24 h and then filtered off. Upon standing the solution 2 weeks at 4 °C, crystals were formed, filtered off, washed with methanol and dried in air (0.035 g, 25.2% yield).
2227
Table 1 Crystal data, data collection and refinement for [Zn(9-EtA–N7)Cl3](9EtAH) Empirical formula Formula weight (g mol1) T (K) Wavelength Crystal system/space group ˚) a (A ˚) b (A ˚) c (A b (°) ˚ 3) Volume (A Z No. molecules per asymmetric unit Dx (calc.) (mg m3) F(0 0 0) h Range for data collection (°) Index ranges
Reflections collected Independent reflections Absorption correction Refinement method Data/restraints/parameters Goodness-of-fit on F2 Final R indices [I > 2r(I)] R indices (all data) ˚ 3) Largest diff. peak and hole (e A
C14H19Cl3N10Zn 499.11 100(2) ˚ 1.54178 A Monoclinic/P21/c 6.61530(10) 27.5875(5) 11.2153(2) 95.0200(10) 2038.94(6) 4 1 1.626 1016 3.20–70.51 8 6 h 6 7, 32 6 k 6 33, 13 6 l 6 13 18983 3830 [Rint = 0.0338] Semi-empirical from equivalents Full-matrix least-squares on F2 3830/0/329 1.152 R1 = 0.0297, wR2 = 0.0789 R1 = 0.0303, wR2 = 0.0794 0.440 and 0.303
Table 2 ˚ ) and angles (°) for compound [Zn(9-EtA– Selected distances (A N7)Cl3](9-EtAH) obtained from the X-ray diffraction analysis and ab initio calculations X-ray Zn(1)–N(7) Zn(1)–Cl(1) Zn(1)–Cl(3) Zn(1)–Cl(2) C(2)–N(3) C(2)–N(1) C(4)–N(3) C(4)–N(9) C(4)–C(5) C(5)–N(7) C(5)–C(6) C(6)–N(6) C(6)–N(1) C(8)–N(7) C(8)–N(9) C(9)–N(9) N(7)–Zn(1)–Cl(1) N(7)–Zn(1)–Cl(3) Cl(1)–Zn(1)–Cl(3) N(7)–Zn(1)–Cl(2) Cl(1)–Zn(1)–Cl(2) Cl(3)–Zn(1)–Cl(2) C(2)–N(1)–C(6) C(2B)–N(1B)–C(6B)
2.0354(16) 2.2471(5) 2.2527(5) 2.2890(5) 1.331(3) 1.344(3) 1.343(2) 1.373(3) 1.384(3) 1.394(2) 1.408(3) 1.340(3) 1.358(2) 1.322(3) 1.356(2) 1.477(3) 108.63(5) 106.50(5) 116.25(2) 108.96(5) 107.667(19) 108.67(2) 118.75(18) 124.67(18)
Ab initio 1.987 2.399 2.211 2.209 1.320 1.372 1.348 1.376 1.392 1.377 1.414 1.319 1.387 1.328 1.362 1.448 106.40 107.86 111.92 112.24 105.09 113.16 118.93 125.01
2228
P. Amo-Ochoa et al. / Journal of Inorganic Biochemistry 99 (2005) 2226–2230
at the N(1) position of the base. There are no unusual features in the geometry of the adenine ligand compared to other metal adenine complexes. The distance Zn–N(7) ˚ is one of the shortest found in analogous of 2.0354(16) A ˚ the mean Zn– adenine Zn(II) complexes, being 2.072 A N(7) distance of the adenine derivatives found in the CCDC [23]. The Zn–Cl(1), Zn–Cl(2) and Zn–Cl(3) dis˚ fall in tances of 2.2471(5), 2.2890(5) and 2.2527(5) A the expected range found in these complexes in which ˚ [23]. Due to protonthe mean Zn–Cl distance is 2.241 A ation at N(1B), the angle C(2B)–N(1B)–C(6B) of the 9-EtAH+ [124.67(18)°] is one of the largest angles described for protonated adenine [23]. It is noticeable that Zn(II) binds to the N(7) of adenine and the cation is located 22° out of the plane defined by the coordinated nucleobase. An intramolecular N(6)–H Cl(2)–Zn H-bond ˚ and almost lininteraction (N(1B)–Cl(2) = 3.1432(18) A ear) is observed in the anionic complex giving an indirect chelation. This type of chelation has been already described for analogous tetrahedral complexes of Zn(II)
containing coordinated chlorine [24]. This indirect chelation may be of importance in the stabilization of the Zn(II)–adenine interaction in DNA. In the crystal network two different types of intermolecular interactions are found: an extended H-bonding network (Table S1) and p–p stacking interactions between the adenine ligands. Intermolecular H-bonds between N(1B)H and Cl(2) and N(6B)H and Cl(1) atoms are present, with distances of 3.1432(18) and ˚ . Self-association between adenine–adeni3.3840(19) A nium bases with asymmetric hydrogen bonds between the N(7B) and N(6)H and N(6B)H and N(1) sites and ˚ , respectively, distances being 2.986(3) and 2.892(3) A take place leading to a polymeric ribbon-like 1D supramolecular arrangement (Fig. 1(a) and (b)). The bases are virtually flat (maximum deviation of atoms from best ˚ ) (Fig. 1(c)). Of the feasible types of adeplane 60.03 A nine–adenine self-association base pairs represented in Scheme 1, (ii) and (iii) are also suitable for adenine– adeninum pairing. In the title complex the coordinate adenine associates to adeninium via N(1)-amino, N(7)-
Fig. 1. (a) H-bonds in compound [Zn(9-EtA–N7)Cl3](9-EtAH). (b) View of the polymeric chain. (c) Detail of the planarity between the nucleobases in the polymeric chain. (d) View down the crystallographic c-axis of the packing of [Zn(9-EtA–N7)Cl3](9-EtAH).
P. Amo-Ochoa et al. / Journal of Inorganic Biochemistry 99 (2005) 2226–2230
2229
Scheme 1. Representation of the feasible adenine–adenine self-association base pairs.
Fig. 2. Stacking of adenine–adeninium in compound [Zn(9-EtA–N7)Cl3](9-EtAH).
amino type (iii). The data base of non-canonical base pairs [25] gives an example of an analogous adenine– adeninium base pair found in the crystal structure of the 30 S ribosomal subunit [26]. A partial p-stacking between adenine and adeninium is observed with a stack˚ (Fig. 2). ing distance of 3.4 A In order to verify stabilization of the adenine–adeninium base pairs by coordination of Zn(II) to N(7) of adenine, ab initio calculations have been performed. A conjugate gradient optimization of the geometry proceeded from the crystal data for [Zn(9-EtA–N7)Cl3](9EtAH) as the starting structure. The compound presents a large energy difference between the highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO) of 1.59 eV (Figure S2), which is an indication of its stability. In Table 2, the selected data obtained from X-ray diffraction are listed together with those obtained by ab initio calculations. The optimized structure shows basically the same structural features than the one obtained by X-ray diffraction (Fig-
ure S3). The small variations observed can be partially a consequence of several intermolecular interactions. The improvement of the intermolecular binding energy due the coordination of ZnCl 3 fragment to N(7) of 9-EtA has been investigated. We start by evaluating the formation energy of the [9-EtA Æ 9-EtAH+] obtaining 0.63 eV. The calculated formation energy of the deprotonated [9EtA Æ 9-EtA] pair gives a value of 0.23 eV. Therefore, protonation at N(1) of 9-EtA produce a significant stabilization of this base pair. Calculations perform on [Zn(9-EtA–N7)Cl3](9-EtAH) give an increasing of the total intermolecular binding energy to 0.70 eV. Therefore, we find that the coordination of ZnCl 3 to N(7) of adenine leads to a further stabilization of [9-EtA Æ 9-EtAH+]. This indicates that the [Zn(9-EtA– N7)Cl3](9-EtAH) would be energetically more stable than [9-EtA Æ 9-EtAH+]. Ab initio calculations for the [Zn(H2O)5A Æ A] (A = adenine) in reverse Hoogsteen orientation (Scheme 1, iii) [27], shows that the adenine amino group destabilizes binding of Zn(II) cation to
2230
P. Amo-Ochoa et al. / Journal of Inorganic Biochemistry 99 (2005) 2226–2230
N(7) due to a repulsive interaction between this group and the water ligand, therefore our results indicate that the coordination sphere of the metal cation appears to be an important factor in the stabilization of these systems. Acknowledgements Financial support from UAM (CS13-541A-9-640), MAT (2004-05589-C02-02) and BFM2002-10510-E. We thank Prof. J.M. Soler for theirs comments. Appendix A. Supplementary data Crystallographic data for compound [Zn(9-EtA– N7)Cl3](9-EtAH) has been deposited with the Cambridge Crystallographic Data Centre, CCDC No. CCDC 272222. Fig. 1S gives an ORTEP of compound [Zn(9-EtA–N7)Cl3](9-EtAH). [Zn(9-EtA–N7)Cl3](9EtAH). Fig. 2S give the Eigenvalue spectra (HOMO– LUMO energy gap) of [Zn(9-EtA–N7)Cl3](9-EtAH), [9-EtA Æ 9-EtAH+] and [9-EtA Æ 9-EtA], respectively, and, Fig. 3S the optimized structure of [Zn(9-EtA– N7)Cl3](9-EtAH). Table S1 list the H-bonds found in [Zn(9-EtA–N7)2Cl3](9-EtAH). Details of the synthesis, analytical and spectroscopic data for [Zn(9-EtA– N7)2Cl3](9-EtAH) are also given. Supplementary data associated with this article can be found, in the online version, at doi:10.1016/j.jinorgbio.2005.07.015. References [1] S. Lippard, J.M. Berg, Principles of Bioinorganic Chemistry, University Science Books, Mill Valley, CA, 1994. [2] A. Volbeda, A. Lahm, F. Sakiyama, D. Suck, Embo. J. 10 (1991) 1607–1618.
[3] V. Narasimhan, A.M. Bryan, Inorg. Chim. Acta 91 (1984) L39– L41. [4] G.L. Eichhorn, Y.A. Shin, J. Am. Chem. Soc. 90 (1968) 7323– 7327. [5] A. Houlton, J. Inorg. Biochem. 86 (2001) 58. [6] M.A. Shipman, C. Price, A.E. Gibson, M.R.J. Elsegood, W. Clegg, A. Houlton, Chem. Eur. J. 6 (2000) 4371–4378. [7] C. Bazzicalupi, A. Bencini, E. Berni, A. Bianchi, S. Ciattini, C. Giorgi, P. Paoletti, B. Valtancoli, Eur. J. Inorg. Chem. (2001) 629–632. [8] J.A.R. Navarro, B. Lippert, Coord. Chem. Rev. 186 (1999) 653– 667. [9] F.A.J. Bernues, in: D.M.J.L.F. Eckstein (Ed.), Nucleic Acids and Molecular Biology, Springer, 1995. [10] J.M. Casasnovas, D. Huertas, M. Ortizlombardia, J. Kypr, F. Azorin, J. Mol. Biol. 233 (1993) 671–681. [11] F. Moroni, A. Famulari, M. Raimondi, M. Sabat, J. Phys. Chem. B 107 (2003) 4196–4202. [12] J. Sponer, M. Sabat, L. Gorb, J. Leszczynski, B. Lippert, P. Hobza, J. Phys. Chem. B 104 (2000) 7535–7544. [13] F. Zamora, M. Sabat, Inorg. Chem. 41 (2002) 4976–4977. [14] F. Zamora, M. Sabat, B. Lippert, Inorg. Chim. Acta 267 (1998) 87–91. [15] F. Zamora, M. Kunsman, M. Sabat, B. Lippert, Inorg. Chem. 36 (1997) 1583–1587. [16] F. Zamora, M. Sabat, B. Lippert, Inorg. Chem. 35 (1996) 4858– 4864. [17] E. Gry, Dissertation, University of Zurich, 1991. [18] E. Dubler, Met. Ions Biol. Syst. 32 (1996) 301–338. [19] B. Lippert, Coord. Chem. Rev. 200 (2000) 487–516. [20] J. Maixner, J. Zachova, Acta Crystallogr. C 49 (1993) 927–929. [21] M.R. Taylor, L.M. Vilkins, M.J. Mccall, Acta Crystallogr. C 45 (1989) 1625–1626. [22] M.J. Mccall, M.R. Taylor, Biochim. Biophys. Acta 390 (1975) 137–139. [23] Cambridge Crystallographic Data Base, November 2004. [24] P.T. Muthiah, S.K. Mazumdar, S. Chaudhuri, J. Inorg. Biochem. 19 (1983) 237–246. [25] U. Nagaswamy, N. Voss, Z.D. Zhang, G.E. Fox, Nucl. Acid. Res. 28 (2000) 375–376. [26] A.P. Carter, W.M. Clemons, D.E. Brodersen, R.J. MorganWarren, B.T. Wimberly, V. Ramakrishnan, Nature 407 (2000) 340–348. [27] J. Sponer, M. Sabat, J.V. Burda, J. Leszczynski, P. Hobza, J. Phys. Chem. B 103 (1999) 2528–2534.
Inorganic Biochemistry Journal of Inorganic Biochemistry 99 (2005) 2226–2230 www.elsevier.com/locate/jinorgbio
Stabilization of the non-canonical adenine–adeninium base pair by N(7) coordination of Zn(II) Pilar Amo-Ochoa a, Simone S. Alexandre b, Ce´sar Pastor c, Fe´lix Zamora
d,*
a
c
Departamento de Tecnologı´a Industrial, Universidad Alfonso X ‘‘El Sabio’’, 28691 Villanueva de la Can˜ada, Madrid, Spain b Departamento de Fı´sica de la Materia Condensada, Universidad Auto´noma de Madrid, 28049 Madrid, Spain Servicio Interdepartamental de Apoyo a la Investigacio´n (rayos-X), Universidad Auto´noma de Madrid, 28049 Madrid, Spain d Departamento de Quı´mica Inorga´nica, Facultad de Ciencias, Universidad Auto´noma de Madrid, 28049 Madrid, Spain Received 24 May 2005; received in revised form 26 July 2005; accepted 27 July 2005 Available online 23 September 2005
Abstract A new zinc (II) compound with 9-ethyladenine (9-EtA) of formula [Zn(9-EtA–N7)Cl3](9-EtAH) has been synthesized and characterized by X-ray diffraction. Its X-structure consists of an Zn(II) anionic complex and 9-ethyladeninium as counteranion. The Zn(II) complex shows a distorted tetrahedral geometry in which three Cl and an 9-EtA coordinates through N(7) position are the ligands. An indirect chelation via intramolecular H-bond between N(6)H and an Cl ligand is present in the complex. The network of [Zn(9-EtA–N7)Cl3](9-EtAH) shows interesting features. Thus, self-association of coordinated adenine–adeninium takes place by H-bonding of N(6)–H N(1) and N(6)–H N(7), leading to a polymeric ribbon-like 1D supramolecular arrangement. Ab initio calculations have been applied in order to study the stability of the adenine–adeninium interaction due to the coordination of the Zn(II) to the N(7) position and to compare experimental and theoretical structural data. Ó 2005 Elsevier Inc. All rights reserved. Keywords: Zn(II)–nucleobases; Supramolecular assemblies; Crystal structure; Ab initio calculations
The interaction of metal ions with DNA and its constituents is of considerable interest due to the biological significance of theses studies. Zinc is considered as an essential biological element, presents in a number of proteins, including some interacting with DNA [1]. In addition, there are several biological processes in which direct interactions between zinc ions and nucleic acids are encountered. Zn(II) ions are involved in processes of DNA recognition, DNA hydrolysis, DNA B ! Z transitions, DNA unwinding and rewinding, among others [2–4]. The role of nucleobases in the recognition process has attracted attention since these molecules posses several functions which can be used to form hydrogen-bonding *
Corresponding author. Tel.: +34 914973962; fax: +34 914974833. E-mail address: [email protected] (F. Zamora).
0162-0134/$ - see front matter Ó 2005 Elsevier Inc. All rights reserved. doi:10.1016/j.jinorgbio.2005.07.015
or metal-binding. Nucleobases provide interesting building blocks for forming extended structures, not only by the multiple possibilities in which bases may interact by H-bonds, but also for the possible p-stacking between them [5]. Particularly, the well-known ability of adenine and guanine to form hydrogen bonds with other nucleobases can allow the formation of supramolecular structures with chemical and biological interest [6,7]. Coordination of metal ions to nucleobases can modify the usual H-bond interactions between bases, allowing new arrangements and stabilizing certain types of noncanonical base–base associations [8]. It has been observed that Zn(II)–nucleobase interactions are essential for the stabilization of non-canonical DNA structures such as triplexes and hairpins [9]. Zinc is also important for the stabilization of purine Æ purine–pyrimidine DNA triplexes [10]. Ab initio calculations have shown that
P. Amo-Ochoa et al. / Journal of Inorganic Biochemistry 99 (2005) 2226–2230
coordination of Zn(II) to N(7) of adenine causes stabilization of the non-canonical guanine–adenine base pairs [11]. It has been also proven by theoretical studies that, when guanine is metalated at N(7), several guanine– nucleobase pairs undergo stabilization without any major change in the geometry of the guanine [11,12]. However, the number reports on structural models of Zn(II) binding to nucleic acids is still scarce. As a continuation of our research project in the group-12 metal ion interactions with nucleobases [13–16], we now report on the synthesis of a new Zn(II)-9-ethyladenine compound, its structural study by X-ray diffraction, and ab initio calculations on the stabilization induced by the Zn(II) coordination to the base in the non-canonical A Æ AH+ base pair present in this compound. The reactions between ZnCl2 and 9-ethyladenine (9EtA), under several conditions and stoichiometries (see Sup. Mat.), do not allow us identifying any pure compound. However, in the reaction between [ZnCl2(6-MPH)2] Æ MeOH [17,18] and 9-EtA allows to characterize the new compound [Zn(9-EtA–N7)Cl3](9-EtAH) by substitution the 6-mercaptopurine (6-MPH) in the mentioned complex.1 Adenine has proved to be a very versatile ligand providing, at physiological pH, potential three binding sites (N1,N3,N7). The N(1) position is the preferred metal-binding site at neutral pH, while the N(7) position is the preferred one in strong acidic conditions, when N(1) is protonated [19]. These facts have specifically been observed for Zn(II)-adenine complexes, in which it has been described that coordination at N(7) takes place when the adenine is protonated (strong acid conditions, 2 M HCl) [20,21] while coordination at N(1) is observed under slight acid conditions [22]. A search in the Cambridge Crystallographic Data Centre [23], of Zn(II) complexes of adenine nucleobase, found 16 examples, being the coordination of Zn(II) to N(7) the most usual binding mode. However, in the complexes showing Zn(II) coordinated to N(7), the N(1) atom is protonated. Details of the data collection and refinement of [Zn(9EtA–N7)Cl3](9-EtAH) are given in Table 1. In Table 2, a selection of distances and angles are listed. The molecular structure consists on a distorted tetrahedral coordination geometry around the Zn(II) (Figure S1), with the metal to donor atom angles ranging between 106.5° and 116.2° (Table 2). Zn(II) coordinates to 9ethyladenine through N(7) and the remaining sites of the coordination sphere are completed with three chlorine ligands. The anionic complex shows as counterion an 9-ethyladeninium cation which presents the proton 1
9-EtA (0.068 g, 0.42 mmol) and [ZnCl 2 (6-MPH) 2 ] Æ MeOH (0.125 g, 0.28 mmol) were stirred in methanol (20 mL) at 70 °C for 24 h and then filtered off. Upon standing the solution 2 weeks at 4 °C, crystals were formed, filtered off, washed with methanol and dried in air (0.035 g, 25.2% yield).
2227
Table 1 Crystal data, data collection and refinement for [Zn(9-EtA–N7)Cl3](9EtAH) Empirical formula Formula weight (g mol1) T (K) Wavelength Crystal system/space group ˚) a (A ˚) b (A ˚) c (A b (°) ˚ 3) Volume (A Z No. molecules per asymmetric unit Dx (calc.) (mg m3) F(0 0 0) h Range for data collection (°) Index ranges
Reflections collected Independent reflections Absorption correction Refinement method Data/restraints/parameters Goodness-of-fit on F2 Final R indices [I > 2r(I)] R indices (all data) ˚ 3) Largest diff. peak and hole (e A
C14H19Cl3N10Zn 499.11 100(2) ˚ 1.54178 A Monoclinic/P21/c 6.61530(10) 27.5875(5) 11.2153(2) 95.0200(10) 2038.94(6) 4 1 1.626 1016 3.20–70.51 8 6 h 6 7, 32 6 k 6 33, 13 6 l 6 13 18983 3830 [Rint = 0.0338] Semi-empirical from equivalents Full-matrix least-squares on F2 3830/0/329 1.152 R1 = 0.0297, wR2 = 0.0789 R1 = 0.0303, wR2 = 0.0794 0.440 and 0.303
Table 2 ˚ ) and angles (°) for compound [Zn(9-EtA– Selected distances (A N7)Cl3](9-EtAH) obtained from the X-ray diffraction analysis and ab initio calculations X-ray Zn(1)–N(7) Zn(1)–Cl(1) Zn(1)–Cl(3) Zn(1)–Cl(2) C(2)–N(3) C(2)–N(1) C(4)–N(3) C(4)–N(9) C(4)–C(5) C(5)–N(7) C(5)–C(6) C(6)–N(6) C(6)–N(1) C(8)–N(7) C(8)–N(9) C(9)–N(9) N(7)–Zn(1)–Cl(1) N(7)–Zn(1)–Cl(3) Cl(1)–Zn(1)–Cl(3) N(7)–Zn(1)–Cl(2) Cl(1)–Zn(1)–Cl(2) Cl(3)–Zn(1)–Cl(2) C(2)–N(1)–C(6) C(2B)–N(1B)–C(6B)
2.0354(16) 2.2471(5) 2.2527(5) 2.2890(5) 1.331(3) 1.344(3) 1.343(2) 1.373(3) 1.384(3) 1.394(2) 1.408(3) 1.340(3) 1.358(2) 1.322(3) 1.356(2) 1.477(3) 108.63(5) 106.50(5) 116.25(2) 108.96(5) 107.667(19) 108.67(2) 118.75(18) 124.67(18)
Ab initio 1.987 2.399 2.211 2.209 1.320 1.372 1.348 1.376 1.392 1.377 1.414 1.319 1.387 1.328 1.362 1.448 106.40 107.86 111.92 112.24 105.09 113.16 118.93 125.01
2228
P. Amo-Ochoa et al. / Journal of Inorganic Biochemistry 99 (2005) 2226–2230
at the N(1) position of the base. There are no unusual features in the geometry of the adenine ligand compared to other metal adenine complexes. The distance Zn–N(7) ˚ is one of the shortest found in analogous of 2.0354(16) A ˚ the mean Zn– adenine Zn(II) complexes, being 2.072 A N(7) distance of the adenine derivatives found in the CCDC [23]. The Zn–Cl(1), Zn–Cl(2) and Zn–Cl(3) dis˚ fall in tances of 2.2471(5), 2.2890(5) and 2.2527(5) A the expected range found in these complexes in which ˚ [23]. Due to protonthe mean Zn–Cl distance is 2.241 A ation at N(1B), the angle C(2B)–N(1B)–C(6B) of the 9-EtAH+ [124.67(18)°] is one of the largest angles described for protonated adenine [23]. It is noticeable that Zn(II) binds to the N(7) of adenine and the cation is located 22° out of the plane defined by the coordinated nucleobase. An intramolecular N(6)–H Cl(2)–Zn H-bond ˚ and almost lininteraction (N(1B)–Cl(2) = 3.1432(18) A ear) is observed in the anionic complex giving an indirect chelation. This type of chelation has been already described for analogous tetrahedral complexes of Zn(II)
containing coordinated chlorine [24]. This indirect chelation may be of importance in the stabilization of the Zn(II)–adenine interaction in DNA. In the crystal network two different types of intermolecular interactions are found: an extended H-bonding network (Table S1) and p–p stacking interactions between the adenine ligands. Intermolecular H-bonds between N(1B)H and Cl(2) and N(6B)H and Cl(1) atoms are present, with distances of 3.1432(18) and ˚ . Self-association between adenine–adeni3.3840(19) A nium bases with asymmetric hydrogen bonds between the N(7B) and N(6)H and N(6B)H and N(1) sites and ˚ , respectively, distances being 2.986(3) and 2.892(3) A take place leading to a polymeric ribbon-like 1D supramolecular arrangement (Fig. 1(a) and (b)). The bases are virtually flat (maximum deviation of atoms from best ˚ ) (Fig. 1(c)). Of the feasible types of adeplane 60.03 A nine–adenine self-association base pairs represented in Scheme 1, (ii) and (iii) are also suitable for adenine– adeninum pairing. In the title complex the coordinate adenine associates to adeninium via N(1)-amino, N(7)-
Fig. 1. (a) H-bonds in compound [Zn(9-EtA–N7)Cl3](9-EtAH). (b) View of the polymeric chain. (c) Detail of the planarity between the nucleobases in the polymeric chain. (d) View down the crystallographic c-axis of the packing of [Zn(9-EtA–N7)Cl3](9-EtAH).
P. Amo-Ochoa et al. / Journal of Inorganic Biochemistry 99 (2005) 2226–2230
2229
Scheme 1. Representation of the feasible adenine–adenine self-association base pairs.
Fig. 2. Stacking of adenine–adeninium in compound [Zn(9-EtA–N7)Cl3](9-EtAH).
amino type (iii). The data base of non-canonical base pairs [25] gives an example of an analogous adenine– adeninium base pair found in the crystal structure of the 30 S ribosomal subunit [26]. A partial p-stacking between adenine and adeninium is observed with a stack˚ (Fig. 2). ing distance of 3.4 A In order to verify stabilization of the adenine–adeninium base pairs by coordination of Zn(II) to N(7) of adenine, ab initio calculations have been performed. A conjugate gradient optimization of the geometry proceeded from the crystal data for [Zn(9-EtA–N7)Cl3](9EtAH) as the starting structure. The compound presents a large energy difference between the highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO) of 1.59 eV (Figure S2), which is an indication of its stability. In Table 2, the selected data obtained from X-ray diffraction are listed together with those obtained by ab initio calculations. The optimized structure shows basically the same structural features than the one obtained by X-ray diffraction (Fig-
ure S3). The small variations observed can be partially a consequence of several intermolecular interactions. The improvement of the intermolecular binding energy due the coordination of ZnCl 3 fragment to N(7) of 9-EtA has been investigated. We start by evaluating the formation energy of the [9-EtA Æ 9-EtAH+] obtaining 0.63 eV. The calculated formation energy of the deprotonated [9EtA Æ 9-EtA] pair gives a value of 0.23 eV. Therefore, protonation at N(1) of 9-EtA produce a significant stabilization of this base pair. Calculations perform on [Zn(9-EtA–N7)Cl3](9-EtAH) give an increasing of the total intermolecular binding energy to 0.70 eV. Therefore, we find that the coordination of ZnCl 3 to N(7) of adenine leads to a further stabilization of [9-EtA Æ 9-EtAH+]. This indicates that the [Zn(9-EtA– N7)Cl3](9-EtAH) would be energetically more stable than [9-EtA Æ 9-EtAH+]. Ab initio calculations for the [Zn(H2O)5A Æ A] (A = adenine) in reverse Hoogsteen orientation (Scheme 1, iii) [27], shows that the adenine amino group destabilizes binding of Zn(II) cation to
2230
P. Amo-Ochoa et al. / Journal of Inorganic Biochemistry 99 (2005) 2226–2230
N(7) due to a repulsive interaction between this group and the water ligand, therefore our results indicate that the coordination sphere of the metal cation appears to be an important factor in the stabilization of these systems. Acknowledgements Financial support from UAM (CS13-541A-9-640), MAT (2004-05589-C02-02) and BFM2002-10510-E. We thank Prof. J.M. Soler for theirs comments. Appendix A. Supplementary data Crystallographic data for compound [Zn(9-EtA– N7)Cl3](9-EtAH) has been deposited with the Cambridge Crystallographic Data Centre, CCDC No. CCDC 272222. Fig. 1S gives an ORTEP of compound [Zn(9-EtA–N7)Cl3](9-EtAH). [Zn(9-EtA–N7)Cl3](9EtAH). Fig. 2S give the Eigenvalue spectra (HOMO– LUMO energy gap) of [Zn(9-EtA–N7)Cl3](9-EtAH), [9-EtA Æ 9-EtAH+] and [9-EtA Æ 9-EtA], respectively, and, Fig. 3S the optimized structure of [Zn(9-EtA– N7)Cl3](9-EtAH). Table S1 list the H-bonds found in [Zn(9-EtA–N7)2Cl3](9-EtAH). Details of the synthesis, analytical and spectroscopic data for [Zn(9-EtA– N7)2Cl3](9-EtAH) are also given. Supplementary data associated with this article can be found, in the online version, at doi:10.1016/j.jinorgbio.2005.07.015. References [1] S. Lippard, J.M. Berg, Principles of Bioinorganic Chemistry, University Science Books, Mill Valley, CA, 1994. [2] A. Volbeda, A. Lahm, F. Sakiyama, D. Suck, Embo. J. 10 (1991) 1607–1618.
[3] V. Narasimhan, A.M. Bryan, Inorg. Chim. Acta 91 (1984) L39– L41. [4] G.L. Eichhorn, Y.A. Shin, J. Am. Chem. Soc. 90 (1968) 7323– 7327. [5] A. Houlton, J. Inorg. Biochem. 86 (2001) 58. [6] M.A. Shipman, C. Price, A.E. Gibson, M.R.J. Elsegood, W. Clegg, A. Houlton, Chem. Eur. J. 6 (2000) 4371–4378. [7] C. Bazzicalupi, A. Bencini, E. Berni, A. Bianchi, S. Ciattini, C. Giorgi, P. Paoletti, B. Valtancoli, Eur. J. Inorg. Chem. (2001) 629–632. [8] J.A.R. Navarro, B. Lippert, Coord. Chem. Rev. 186 (1999) 653– 667. [9] F.A.J. Bernues, in: D.M.J.L.F. Eckstein (Ed.), Nucleic Acids and Molecular Biology, Springer, 1995. [10] J.M. Casasnovas, D. Huertas, M. Ortizlombardia, J. Kypr, F. Azorin, J. Mol. Biol. 233 (1993) 671–681. [11] F. Moroni, A. Famulari, M. Raimondi, M. Sabat, J. Phys. Chem. B 107 (2003) 4196–4202. [12] J. Sponer, M. Sabat, L. Gorb, J. Leszczynski, B. Lippert, P. Hobza, J. Phys. Chem. B 104 (2000) 7535–7544. [13] F. Zamora, M. Sabat, Inorg. Chem. 41 (2002) 4976–4977. [14] F. Zamora, M. Sabat, B. Lippert, Inorg. Chim. Acta 267 (1998) 87–91. [15] F. Zamora, M. Kunsman, M. Sabat, B. Lippert, Inorg. Chem. 36 (1997) 1583–1587. [16] F. Zamora, M. Sabat, B. Lippert, Inorg. Chem. 35 (1996) 4858– 4864. [17] E. Gry, Dissertation, University of Zurich, 1991. [18] E. Dubler, Met. Ions Biol. Syst. 32 (1996) 301–338. [19] B. Lippert, Coord. Chem. Rev. 200 (2000) 487–516. [20] J. Maixner, J. Zachova, Acta Crystallogr. C 49 (1993) 927–929. [21] M.R. Taylor, L.M. Vilkins, M.J. Mccall, Acta Crystallogr. C 45 (1989) 1625–1626. [22] M.J. Mccall, M.R. Taylor, Biochim. Biophys. Acta 390 (1975) 137–139. [23] Cambridge Crystallographic Data Base, November 2004. [24] P.T. Muthiah, S.K. Mazumdar, S. Chaudhuri, J. Inorg. Biochem. 19 (1983) 237–246. [25] U. Nagaswamy, N. Voss, Z.D. Zhang, G.E. Fox, Nucl. Acid. Res. 28 (2000) 375–376. [26] A.P. Carter, W.M. Clemons, D.E. Brodersen, R.J. MorganWarren, B.T. Wimberly, V. Ramakrishnan, Nature 407 (2000) 340–348. [27] J. Sponer, M. Sabat, J.V. Burda, J. Leszczynski, P. Hobza, J. Phys. Chem. B 103 (1999) 2528–2534.