Antiferromagnetic Coupling of Stacked Cu^II–Salen Complexes in DNA

Abstract

A pretty couple: Two copper–salen metal–base pairs were incorporated into a DNA double helix in neighboring positions (see picture). The two paramagnetic CuII ions are antiferromagnetically coupled, and the exchange coupling constant is −2J=22.4 cm−1. The dipolar coupling constant yielded a Cu⋅⋅⋅Cu distance of 3.7 Å, which is comparable to the base-pair distance in natural B-type DNA. On the way to novel bottom-up generated functional materials that might play a key role in future nanotechnology, the use of DNA has become a major strategy.1 The relative ease of automated DNA synthesis has been exploited to build a wide range of two- and three-dimensional structures from unmodified2 and modified DNA strands.3 Currently, the implementation of real functions such as long-distance electron transfer or molecular magnetism is pursued as the next major step. As a promising candidate for the realization of such functions, the concept of metal–base pairing has been developed.4 In metal–base pairs, the natural hydrogen-bonding interactions between the complementary nucleobases are substituted by coordinative forces between ligand-modified nucleosides and appropriate transition-metal ions. It has been shown that stacks of up to 10 metal ions such as CuII can be incorporated inside DNA double helices that are modified with ligands such as hydroxypyridone (H) or N,N′-bis(salicylidene)ethylene diamine (salen, S).5 Apart from the superior duplex stabilization that was achieved using these systems, the positioning of a number of paramagnetic ions inside these DNA materials was envisioned to yield DNA strands with ferro- or antiferromagnetic behavior. The basis for this behavior is the electron–electron spin–spin exchange coupling J between the CuII ions.6 An understanding of structural correlations such as intermetallic distance and base sequence giving rise to the sign and size of J is a prerequisite for the rational design of magnetic DNA strands. A first step in this direction was the observation of an overall ferromagnetic coupling in a stack of five CuII–hydroxypyridone [H2(Cu)] metal–base pairs by Shionoya and co-workers.7 Herein, we introduce electron paramagnetic resonance (EPR) based magnetic measurements performed on the CuII–salen metal–base pairs [S(Cu)] inside the DNA double helix (Figure 1).8 Interestingly, changing the ligand system from hydroxypyridone to salen induces a profound change to an overall antiferromagnetic coupling. In the H2(Cu) metal–base pair, two separate bidentate hydroxypyridone ligands coordinate to the CuII ion through four oxygen atoms. In contrast, the salen ligand S is a tetradentate N2O2 donor, which is realized as a cross-link between the two strands of the DNA duplex.9 Although in both systems, CuII is coordinated in a square-planar fashion inside the DNA double helix, subtle differences of the coordinating ligands seem to effect the magnetic interaction of neighboring metal–base pairs in a tremendous way. Structure of the S(Cu) metal–base pair (nuclei giving rise to hyperfine splitting highlighted in blue), sequences of the examined duplexes containing one (1) and two (2) CuII ions, and schematic depiction of the envisioned structures of the metal containing double strands. As a reference system and to check whether the CuII–salen structure is preserved in DNA, low-temperature continuous-wave (CW) X-band EPR spectra were acquired from DNA 1 containing a single CuII–salen base pair. A representative EPR spectrum of 1 is displayed in Figure 2 a and shows the characteristic features of a square-planar CuII system with S=1/2. Simulating the spectrum yields the spin Hamiltonian parameters summarized in Table 1. The hyperfine and super hyperfine features are well reproduced and consistent with the expected interactions of the CuII ion with two equivalent nitrogen atoms with nuclear spins I(14N)=1 and two equivalent and weakly coupled hydrogen atoms with nuclear spins of I(1H)=1/2 (exemplified in Figure 1). The axial coordination symmetry and the EPR parameters fit to those reported for reported pure inorganic CuII–salen structures.10 This result confirms that upon self-assembled duplex formation, the geometry of the inorganic complex is preserved. CW X-band EPR spectra of a) 1 and b) 2 at 77 K (black) overlaid with the simulations (gray). The inset in (a) shows an enlargement of the perpendicular region and the inset in (b) shows the half-field signal recorded at 14 K. S(Cu) DNA 1 DNA 2 giso 2.094 2.093 2.098 g∥ 2.194 2.194 2.194 g⊥ 2.041 2.042 2.054 Aiso(Cu2+) [G] 90.4 91.4 91.9 A∥;⊥(Cu2+) [G] 221.8; 31.8 208.5; 32.8 210.0; 32.8 A(14N) [G] 15.5 16.0 16.0 A(1H) [G] 7.1 7.5 7.5 D [G] – – 370±10 Javerage [cm−1] – – −11.2±1 In Figure 3, the half-field signal intensity measured as peak-to-peak height of the predominant peak is plotted against T for DNA duplex 2. Best fits to Eq. (2) reveal an exchange coupling constant of J=−10.8±0.2 cm−1. Using a plot of the doubly integrated intensity against T results in a similar value of J=−11.6±0.2 cm−1 (data not shown, Javerage=−11.2±1 cm−1). Thus, stacking of two CuII–salen base pairs leads to antiferromagnetic coupling, whereas ferromagnetic coupling was reported for stacked CuII–hydroxypyridone base pairs.7 Such a change in magnetism upon switching from CuII–hydroxypyridone to CuII–salen base pairs was predicted recently in two independent DFT studies by Nakanishi et al.14 and by Mallajosyula and Pati.15 In the latter work, an exchange coupling constant of J=−10.5 cm−1 was calculated for the CuII–salen system based on a predicted square-planar geometry and a Cu⋅⋅⋅Cu distance of 3.7 Å. The magnitude and sign of J as well as the geometry agree very well with the EPR data reported herein, which renders also the suggested mechanisms as very likely. The pairwise arrangement and the rather long Cu⋅⋅⋅Cu distance in the S(Cu)–DNA system leads to a weaker and antiferromagnetic coupling due to a direct cation–cation exchange-coupling mechanism, which is in agreement with the Goodenough– Kanamori rules.15 In contrast, the so-called four-atom {Cu2O2} convex quadrangle structure in the H2(Cu) system arranges the magnetic orbitals in an orthogonal fashion, which suppresses the antiferromagnetic interaction and together with the shorter Cu⋅⋅⋅Cu distance of 3.2 Å leads to a strong ferromagnetic interaction. It seems that the oxygen atom contacts with the neighboring bases to form the {Cu2O2} quadrangle, which provides a bridge for exchange pathways in the H2(Cu) system, whereas such contacts could not be resolved in the S(Cu) system.15 An additional ligand such as water bridging the two copper ions in either of the two systems, [H2(Cu)] or [S(Cu)], could not be verified either by high-resolution ESI mass spectra or from the EPR spectra. This result shows that the incorporation of stacked CuII–base pairs into DNA does not automatically result in ferromagnetic coupling and precise experimental and theoretical studies are required. Intensity of the half-field signal of DNA 2 plotted versus temperature T (circles) and best fit to equation (2) (solid line). In summary, we characterized the magnetic properties of novel metal–DNA species containing one and two CuII ions. The data show that the axial, square-planar geometry of the original inorganic complex is preserved inside the DNA duplex. Furthermore, the exchange coupling between the two paramagnetic metal–base pairs inside the DNA strand was quantified by temperature-dependent CW EPR measurements and yielded an antiferromagnetic exchange coupling constant of Javerage=−11.2±1.0 cm−1. The experimental data provided herein for the S(Cu) DNA and the data reported for the H2(Cu) system are in good agreement with the respective theoretical predictions, thus providing the basis for future investigations of the magnetic properties of artificial metal–DNA complexes. Because of the electron-transfer properties of metal–DNA complexes and the possibility to generate mixed-metal arrays16 in a sequence-specific manner, the present findings are a further step towards the rational construction of devices in the emerging field of molecular spintronics.17 The synthesis and characterization of the DNA duplexes 1 and 2 have been described previously.8 Careful addition of stoichiometric amounts of Cu2+ to a solution of the hybridized DNA duplexes resulted in the exclusive formation of the desired DNA–metal complexes as monitored by ESI-FTICR mass spectrometry and UV spectroscopy. The CW X-band EPR spectra were acquired between 13 K and 150 K in frozen solution on a BRUKER ESP300E spectrometer with a standard rectangular ER4102T cavity equipped with an Oxford Instruments helium cryostat (ESR910/900). In Figure 3, data points below 10 K were omitted because of the strong decrease in signal intensity and a concomitant significant increase in spectral noise below this temperature. Solutions of the DNA–metal complexes (360 μM) in NH4OAc buffer (100 mM) at pH 8 containing ethylenediamine (5 mM) were used. Ethylene glycol (20 % v/v) was added to the aqueous buffer as a cryoprotectant and all samples were stored instantaneously under liquid nitrogen. Simulations of the spectra were preformed with WINEPR SimFonia 1.25 and EasySpin 2.51.18 In the simulations of DNA 1, linewidths of 7 G for the x and y and 32 G for the z directions were used. The ratio between Lorentzian and Gaussian line shapes was set to 0.3. For the simulations of the EPR spectrum of DNA 2, a spin-Hamiltonian with two interacting S=1/2 centers including the terms SDS and JSS was used. The line widths were 80 G for x and y and 65 G for the z directions.