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Corral Simón, E. (2007, September 25). Ruthenium polypyridyl complexes with anticancer properties. Retrieved from https://hdl.handle.net/1887/12358
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Appendix. Nucleic acids in two
dimensions: layers of base pairs linked
by carboxylate *
The formation of a planar 2D hydrogen-bonded network between DNA bases and formate residues is reported, leading to unprecedented parallel sheets of DNA analogues.
* This appendix is based on Corral, E.; Kooijman, H.; Spek, A.L.; Reedijk, J., New J. Chem., 2007, 31, 21-24.
A.1. Introduction
Nucleic acids, such as DNA, RNA and their fragments, occur naturally in three- dimensional chain-based structures derived from the double chain structure first described by Watson and Crick in 1953.1 The principal forces holding this spatial organization together are the Watson-Crick base pairing and the stacking between the bases; the chains are built of sugar-phosphate links. Several deviations of these structures are known to occur naturally. These abnormalities are the subject of intense studies and in some cases they are provoked in search for therapeutic applications.2-5 Bends and kinks usually arise as a consequence of the presence of special sequences or mismatching, for instance in some RNA´s.6-8 Triple-helix chains are also known,2, 4 as well as some quadruplex structures,3, 9-
12 knots and features such as hammerhead and other junctions.5 In all cases the 1D organisation is one of the factors that determine the structure.
Much work has been done to create new artificial base-association ways. Different approaches, such as metal-assisted hydrogen-bonding13, 14 and incorporation of artificial bases into DNA,15, 16 have been used to develop new DNA base pairs or duplexes, many of which can be enzymatically replicated in search for possible new biological applications.17
More recently research has been reported on the synthesis of ion channels that consist of self-assembled supramolecular rosettes. These rosettes contain nucleic acids and other DNA-based artificial nucleosides, which associate with each other in unusual ways. The rosettes pile up due to -stacking.18-20
Following these lines of investigation also some supramolecular helical,21 linear,22 and macrocyclic structures23-25 have been obtained.
So far, a complete 2D organized flat structure of nucleic acid bases has never been achieved by self-assembly of the nucleobases in solution, and it has been questioned whether such a flat structure, with only hydrogen bonding within the plane, would be possible. In fact, when having a close look at the common nucleic acid bases it is not difficult to imagine that such structures should be possible, either with neutral bases or with cationic or anionic bases in combination with small cations or flat anions, respectively.
A.2. Results and discussion
To explore this possibility in detail a simple DNA model base that resembles a nucleotide and that has been used in many model systems, namely 9-ethylguanine,26-28 was selected in combination with the smallest bifunctional flat anion, i.e. formate. Simple
Nucleic Acids in two dimensions: layers of base pairs
modelling shows that in this case all strong H-bond donors and H-bond acceptors would match, originating a H-bond net. Indeed when the 9-ethylguanine (eg, previously abbreviated in this thesis as 9-EtGua) was crystallised from a formic acid solution at a proper concentration at RT, crystals of (H7eg)(HCOO) could be isolated, where the guanine moiety is protonated in position 7 (see Fig.A.1).
Fig.A.1. PLATON projection of (H7eg)(HCOO) showing the hydrogen bonding.
The asymmetric unit contains two (H7eg)(HCOO) ion pairs. The packing environment of these pairs is virtually identical. The formate anion plays an indispensable role in the formation of a hydrogen-bond net (see Table A.1 and Fig.A.2) in which the 9-Ethylguaninium residues are associated to each other by the unusual 12-Trans Sugar Edge/Sugar Edge interactions, as described in the Leontis/Westhof classification.29, 30 These base pairs belong to the so-called class IV from the Saenger classification,31 which a more recent designation classifies as GG N3-amino, symmetric.32 To the best of our knowledge only one example is known of an organism containing this kind of base-pairing in a cellular organelle: the Haloarcula marismortui ribosome, in its pairs G315:G336 and G2428:G2466.33 This base-pair association has never before been achieved artificially
without a simultaneous inclusion of metal atoms in the structure, such as gold or cadmium,34 or the blockage of the N7 of the purine ring with a metal atom or a methyl group.13, 35
Table A.1. Selected distances (Å) and angles (0) in the crystal structure of (H7eg)(HCOO).
Only data for one of the independent ion pairs is given. The atom numbering is indicated in Fig.A.2.
Interatomic distances
Donor-H...Acceptor D..A (Å)
Angles (0)
N(24)-H(24)…O(31II) N(21)-H(21)…O(41I) N(22)-H(22A)…O(42I) N(22)-H(22B)...N(23III)
2.545(3) 2.776(3) 2.883(3) 3.026(3)
N(21)-C(21)-N(22) N(22)-C(21)-N(23) O(41I)-N(21)-C(21) N(22)-O(42I)-C(41I) O(42I)-N(22)-H(22B)
117.0(2) 119.4(2) 116.09(16) 112.04(17) 115.5 (2)
Fig.A.2. Detail of Fig.A.1, with numbering of major atoms. The Roman subscripts are the same as in Table A.1.
Nucleic Acids in two dimensions: layers of base pairs
The nucleoside-formate sheets herein described were found to allow a very close base-pair stacking, with a distance between parallel layers of only 3.288(1) Å (see Fig.A.3) (the distance between base-pair planes in B-DNA is 3.46 Å).
Fig.A.3. Packing of (H7eg)(HCOO), forming parallel layers.
The structure described in this appendix is not the only possible example of 2D nucleoside packing that can be thought of. Current work is focusing on such systems, by changing both the nucleic acid bases and the counter ions. Formate has proven to be a valid example of a counter ion that, due to its simplicity as much as to its planar geometry, could help to build these systems. Although in principle nitrate could also be thought suitable to yield a planar crystal structure, it does not have a hydrophobic part in the proximity of the ethyl group, and cannot form such a lattice. The formate hydrogen, however, fits perfectly in the “gap” existing between the 2 ethyl groups of the neighbouring guanine moieties, while the corresponding nitrate oxygen atom would provoke repulsion forces that would distort the 2D structure.
The self-organisation of organic molecules into non-covalently bonded nanostructures, such as flat solid surfaces, gives structures with a high degree of order, thereby opening a wide range of applications, for example, in electronic and optical devices,36 in corrosion inhibition37 and in supramolecular chemistry.38 In molecular electronics, gold nanoparticles are embedded in ultrathin organic films, which could be used to interconnect gold nanoelectrodes in a molecular-scale electronic device, as suggested by Samorí and co-workers.39
The possible uses of these nucleoside layers in nanotechnology are barely starting to emerge,40 and much research is currently being done in fields such as DNA computation.
DNA biosensors could be made by taking advantage of the specificity in the binding of the base pairs.41, 42
Ribbon-like architectures have been described, which were formed by self-assembly of guanosines in solution and in the solid state.43-45 Different applications of these ribbon structures in fields such as surface chemistry and photochemistry are being studied.46-49 The exploitation of DNA fragments and their mutual hydrogen bonding interactions for material purposes was extensively reviewed by Seeman.50
From a theoretical point of view, this kind of structures is of interest in the study of the emergence of life.51 It has been suggested that purine and pyrimidine monolayers could be candidates for a stationary phase in organic molecule separation systems and as templates for the assembly of higher ordered polymers at the prebiotic solid-liquid interface.52, 53
In conclusion, a new type of arrangement of DNA-base hydrogen bonding in layers is reported, which provides insights in novel templates for nanotechnology based in 2D structures of nucleosides linked by a very simple carboxylate-containing molecule.
A.3. Experimental
Materials and reagents
9-ethylguanine was purchased from Sigma and used as supplied. All other chemicals and solvents were reagent grade commercial materials and used as received, without further purification.
Physical measurements
C, H and N determinations were performed on a Perkin Elmer 2400 Series II analyzer.
NMR spectra were recorded on a Bruker DPX-300 spectrometer operating at a frequency of 300 MHz. Chemical shifts were calibrated against tetramethylsilane (TMS).
Experimental procedure
A 0.014 M solution of 9-ethylguanine in formic acid-benzyl alcohol (1:1) was prepared. A white crystalline solid appeared. The crystals obtained were found to be suitable for X-ray diffraction measurements. The product was collected by filtration,
Nucleic Acids in two dimensions: layers of base pairs
washed with little ice-cold water and dried in vacuo over silica. Anal. Calc. for C7H10N5O·CHO2: C, 42.7; H, 4.9; N, 31.1%. Found: C, 42.4; H, 5.0; N, 30.8%. 1H NMR (DMSO-d6): δ (ppm): 10.46 (1H, s, NH), 8.12 (1H, s, HCOO), 7.67 (1H, s, C(8)H), 6.37 (2H, s, NH2), 3.94 (2H, dd, 7.3 Hz, 14.5 Hz, CH2), 1.31 (3H, t, 7.3 Hz, CH3).
X-ray structural determination
Crystal data: C7H10N5O · CHO2, M = 225.22, triclinic, space group P-1 (No. 2) with a
= 7.4575(12), b = 11.6882(12), c = 12.8664(15) Å, = 114.651(10), = 94.767(11), = 101.729(10)0, V = 980.1(2) Å 3, Z = 4, Dc = 1.5263(3) g cm–3, μ(Mo K) = 0.120 mm–1, T = 150 K, 23598 reflections measured, 3550 independent, Rint = 0.1231 (before detwinning), R = 0.0559. The measured crystal was a twin, with a two-fold rotation around the b + c direction as twin operation. Data were detwinned using PLATON.54 Refinement of 356 parameters converged at a final wR2 value of 0.1540 (all data), R1 = 0.0515 (for 2847 reflections with I > 2(I)), S = 1.085, -0.29 < < 0.27 e Å-3. Crystallographic data (excluding structure factors) for the structure reported in this appendix have been deposited at the Cambridge Crystallographic Data Centre as number CCDC 612070.
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