Adenine Units Research Articles

The Many Facets of Adenine: Coordination, Crystal Patterns, and Catalysis

Canonical purine-pyrimidine base pairs, the key to the complementary hydrogen bonding in nucleic acids, are fundamental molecular recognition motifs crucial for the formation and stability of double-helical DNA. Consequently, focused study and modeling of nucleobase hydrogen-bonding schemes have spawned a vast array of chemical and biophysical investigations. The Watson-Crick, reverse Watson-Crick, Hoogsteen, and reverse Hoogsteen hydrogen-bonding schemes stabilize various nucleic acid structures. As a result, numerous modified bases have been designed to maximize such interactions, addressing specific problems related to base pairing and giving rise to supramolecular ensembles in solution or in the solid state. It is also important to realize that suitably predisposed imino nitrogens and other functional groups present in heterocyclic nucleobases present a versatile molecular framework for the construction of coordination architectures, which may be harnessed to mimic base polyads and higher order nucleic acid structures. Adenine, a purine nucleobase, is an important naturally occurring nitrogen heterocycle present in nucleic acids. It is notable that the adenine unit is also frequently encountered as an inextricable part of enzyme cofactors and second messenger systems, such as NAD(+), FADH(2), and cAMP, which are essential for certain catalytic reactions and biochemical processes. In addition, a crucial catalytic role of the adenine moiety is also observed in group II intron catalysis and at the ribosomal peptidyltransferase center. Such versatile functional roles of the adenine framework serve as an inspiration for addressing research problems, ranging from classical coordination chemistry to the development of new materials. In this Account, we begin by describing the emerging use of adenine nucleobase for the design of metal-nucleobase frameworks. The coordination of metal ions affords a variety of oligomeric and polymeric species; we focus on silver- and copper-based structures and also discuss ferrocenylated adenine tetrads. We then consider the use of supramolecular adenine coordination complexes for transferring molecular properties onto surfaces. This technique is particularly useful for transferring noncovalent interactions, such as van der Waals forces, electrostatic interactions, and hydrogen bonding, to designed architectures in nanoscale applications. Finally, we explore the issue of adenine-based catalytic entities. Here, adenine moieties are first fixed in a polymeric matrix, followed by metalation of the matrix. These metalated adenine-containing polymers are then assayed for catalytic assistance in various chemical and biochemical reactions. Taken together, the versatile coordination abilities and hydrogen-bonding capacity of adenine offer a novel entry point for a natural ligand into materials synthesis.

Effect of stoichiometry on liquid crystalline supramolecular polymers formed with complementary nucleobase pair interactions

AbstractWe report herein studies on the liquid crystalline behavior of a series of supramolecular materials that contain different ratios of two complementary symmetrically‐substituted alkoxy‐bis(phenylethynyl)benzene AA‐ and BB‐type monomers. One monomer has thymine units placed at either end of the rigid mesogenic core, while the other has N6‐(4‐methoxybenzoyl)‐adenine units placed on the ends. Differential scanning calorimetric and polarized optical microscopy studies have been carried out on these systems. These studies show that the material's behavior is strongly dependent on its thermal history. As a result, the materials can exhibit, on heating, either a liquid crystalline phase, a crystalline phase, or the coexistence of crystalline and liquid crystalline regions. © 2006 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 44: 5049–5059, 2006

Microanalysis of oligodeoxynucleotides by cathodic stripping voltammetry at amalgam-alloy surfaces in the presence of copper ions

The application of gold amalgam-alloy electrode (AuAE) for a sensitive voltammetric detection of different oligodeoxynucleotides (ODNs) containing the purine units within the ODN-chains in the presence of copper is described. The detection of ODNs is based on the following procedure: (i) the first step includes an acidic hydrolysis of the ODN (ahODN) samples performing the release of the purine bases from ODN-chain; (ii) the second step includes an electrochemical accumulation of the complex of the purine base residues released from ODN-chain with copper ions Cu(I) (ahODN–Cu(I) complex) at the potential of reduction of copper ions Cu(II) on the amalgam-alloy electrode surfaces; (iii) finally followed the cathodic stripping of the electrochemically accumulated ahODN–Cu(I) complex from the electrode surface. The proposed electrochemical method was used for: (a) detection of different ODN lengths containing only adenine units (the number of adenine units within the ODN-chains was changed from 10 to 80), and (b) determination of the number of purine units within the 30-mer ODNs containing a random sequence segments involving both the purine and pyrimidine units. The intensity of the cathodic stripping current density peak ( j CSP) of the electrochemically accumulated ahODN–Cu(I) complex increased linearly with the increasing number of purine units within the ODN-chains. We observed a good correlation between the percentage content of purine units to the whole length of different 30-mer ODNs and the percentage content of the intensity of the j CSP of the electrochemically accumulated 30-mer ahODN–Cu(I) complexes. The detection of acid hydrolysed 80-mer ( A 80) in the bulk solution and in a 20-μl volume is possible down to 200 pM and 2 nM at the AuAE, respectively. For the shortest 10-mer ( A 10) a detectable value of 5 nM in the bulk solution on the AuAE was observed. The sensitive detection of different ODNs containing the purine units in their chains in the presence of copper can be also performed at the platinum amalgam-alloy (PtAE) and copper amalgam-alloy (CuAE) contrary to a lower sensitivity at the silver amalgam-alloy (AgAE) electrode.

Sensitive determination of oligodeoxynucleotides by anodic adsorptive stripping voltammetry at surface-roughened glassy carbon electrode in the presence of copper

A sensitive voltammetric detection of different oligodeoxynucleotide (ODN) samples at the surface-roughened glassy carbon electrode (GCE) is described. The optimisation of the measurement showed that the most sensitive detection of the ODN samples can be performed at the GCE mechanically polished by abrasion particles with diameter of about 15 μm (15-μm GCE; 1200-grid silicon carbide paper). The heights of the ODN signals at the GCE polished with 1 μm diamond paste (1-μm GCE) were about 22-times less than on the 15-μm GCE. An atomic force microscope (AFM) was used for characterisation of the surface roughness of the mechanically polished GCE by different abrasion particles. The proposed electrochemical method for the detection of different ODNs is based on the following steps: (i) before voltammetric measurement the acidic hydrolysis of the ODN (ahODN) sample was performed; (ii) the second step includes a potential-controlled reduction of Cu(II) and accumulation of the purine base residue–Cu(I) complex (ahODN–Cu(I) complex) at the GCE; (iii) finally, followed the anodic stripping of the electrochemically accumulated ahODN–Cu(I) complex from the GCE. The anodic stripping of the accumulated ahODN–Cu(I) complex produced a well-developed voltammetric signal (peak I) at around +0.28 V. At more positive potentials a second voltammetric signal (peak II) corresponding to the oxidation of adenine residues can be detected. The intensity of peaks I and II of the ahODN–Cu(I) complex increased linearly with the length of ahODNs containing only adenine units. We observed a good correlation between the number of purine units within the ODN-chain and the height of the peak I of the electrochemically accumulated ahODN–Cu(I) complex.

Selective Complexation of N‐Alkylpyridinium Salts: Binding of NAD+ in Water

A new class of receptor molecules is presented that is highly selective for N-alkylpyridinium ions and electron-poor aromatics. Its key feature is the combination of a well-preorganized molecular clip with an electron-rich inner cavity and strategically placed, flanking bis-phosphonate monoester anions. This shape and arrangement of binding sites attracts predominantly flat electron-poor aromatics in water, binds them mainly by pi-cation, pi-pi, CH-pi, and hydrophobic interactions, and leads to their highly efficient desolvation. NAD(+) and NADP, the important cofactors of many redox enzymes, are recognized by the new receptor molecule, which embraces the catalytically active nicotinamide site and the adenine unit. Even nucleosides such as adenosine are likewise drawn into the clip's cavity. Complex formation and structures were examined by one- and two-dimensional NMR spectroscopy, Job plot analyses, and isothermal titration microcalorimetric (ITC) measurements, as well as quantum chemical calculations of (1)H NMR shifts. The new receptor molecule is a promising tool for controlling enzymatic oxidation processes and for DNA chemistry.

Monitoring molecular recognition of the ribosomal decoding site.

Adenine flips out: A combination of X-ray crystallography, 2-aminopurine fluorescence labeling, and the use of aminoglycosides as ligands is exploited to demonstrate conformational transitions in the RNA domain that ensures accurate protein synthesis (see picture). The triggering of a conformational change of an adenine unit in the RNA by ligand binding can be used as the basis of a screening method to discover antibiotics. Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2002/2004/z54217_s.pdf or from the author. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

Synthesis and DNA Binding Property of a Novel Peptide Nucleic Acid that Contains cis-4-Adeninyl-l-prolinol Unit

Abstract A novel oxy-peptide nucleic acid that contains a cis-4-adeninyl-l-prolinol unit in the main chain (PPNA) was synthesized. The peptide nucleic acid with nine adenine units [PPNA(A9)] hybridized with the complementary DNA (T9). The hybrid showed a very sharp melting curve with Tm = 34 °C.

Spectroscopic investigation of nickel cation binding with adenine mononucleotides: stability and structure of the 1:2 complex with adenosine 5′-monophosphate

The interaction of Ni(II) ions with adenine mononucleotides (5′-AMP, 3′-AMP, 2′-AMP, 2′,3′-cAMP, 3′,5′-cAMP) was studied in aqueous solution using Raman spectroscopy and 13C and 31P NMR paramagnetic relaxation measurements. Macrochelate structures were observed to form for all non-cyclic AMPs, with increasing stability in the series: 3′-AMP < 2′-AMP < 5′-AMP. N7 of adenine was found to be the key site of the Ni(II)-adenine interaction for all non-cyclic AMPs. For 2′-AMP, an alternative binding to the pyrimidine ring may also exist. The dependence of Raman spectra on AMP and Ni(II) concentration confirmed the existence of a stable 1 : 2 Ni(II)-(5′-AMP) complex, besides the 1 : 1 complexes. In this complex, the adenine moieties of both 5′-AMP molecules are situated close to Ni(II), and their relative orientations with respect to the cation are very similar. The paramagnetic relaxation enhancements of the carbons indicate that the nickel ion is not located in the plane of the adenine units, but that the line connecting Ni(II) and N7 deviates strongly from the adenine planes. Phosphates are outer-sphere coordinated by the cation. Findings from both methods have led us to propose possible global architectures of the complex.

Binding of Amino-Dialkylated Adenines to Rhenium(III) and Rhenium(IV) Centers.

Amino-dialkylated adenines R(2)AdH (R = Me, Et) react with ReCl(3)(MeCN)(PPh(3))(2) to form mer,cis-ReCl(3)(R(2)AdH)(2)(PPh(3)) complexes. Attempts to protonate the coordinated adenine with HCl led to the oxidized trans-ReCl(4)(R(2)AdH)(PPh(3)) compounds. In both types of complexes, the purine binds via the N3 site of the six-membered ring and makes an intramolecular N9-H.Cl hydrogen bond with a chloride ligand. A material of composition ReCl(4)(R(2)AdH)(MeCN) was obtained by reacting R(2)AdH with cis-ReCl(4)(MeCN)(2). It turned out to be a ReCl(4)[R(2)AdC(Me)=NH] complex containing a cyclic amidine ligand resulting from the insertion of the acetonitrile C&tbd1;N group in the N9-H bond of the N3-coordinated adenine unit. Crystal structures were determined for one compound of each type: ReCl(3)(Me(2)AdH)(2)(PPh(3)).2C(6)H(5)CH(3), triclinic, P&onemacr;, a = 14.181(2) Å, b = 17.591(3) Å, c = 19.015(5) Å, alpha = 76.66(2) degrees, beta = 86.80(2) degrees, gamma = 87.02(1) degrees, Z = 4, R = 0.0606; ReCl(4)(Me(2)AdH)(PPh(3)), triclinic, P&onemacr;, a = 10.391(4) Å, b = 10.801(5) Å, c = 13.651(6) Å, alpha = 89.64(4) degrees, beta = 83.49(3) degrees, gamma = 65.14(4) degrees, Z = 2, R = 0.0432; ReCl(4)[Me(2)AdC(Me)=NH].C(6)H(6).CH(2)Cl(2), monoclinic, P2(1)/c, a = 13.941(3) Å, b = 13.656(3) Å, c = 12.874(2) Å, beta = 105.47(2) degrees, Z = 4, R = 0.0406. Most of the signals in the (1)H NMR spectra of these paramagnetic species could be assigned.

Reaction of the potent bacterial mutagen 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX) with 2'-deoxyadenosine and calf thymus DNA: identification of fluorescent propenoformyl derivatives.

The potent bacterial mutagen and drinking water disinfection byproduct 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX) was reacted with 2'-deoxyadenosine and calf thymus DNA in aqueous solutions at neutral conditions. HPLC analyses of the 2'-deoxyadenosine reaction mixtures showed that two previously unidentified products were formed. The products were isolated by preparative C18 chromatography, and their structures were characterized by UV absorbance, fluorescence emission, 1H and 13C NMR spectroscopy, and mass spectrometry. It was concluded that in both products a propeno bridge had been incorporated between N-1 and N6 of the adenine unit. In one of the products, the propeno bridge carried a formyl group [3-(2'-deoxy-beta-D-ribofuranosyl)-7H-8-formyl[2,1-i]pyrimidopurine++ + (pfA-dR)], and in the other the substituents consisted of a formyl group and a chlorine atom [3-(2'-deoxy-beta-D-ribofuranosyl)-7H-8-formyl-9-chloro[2,1-i]pyrimid opurine (Cl-pfA-dR)]. These novel adducts exhibited fluorescence in the visible region with emission maxima around 460 nm. The yields of the products in reactions performed at pH 7.4 and 37 degrees C were about 0.03 mol %. In reaction of MX with calf thymus DNA, the adduct pfA-dR was formed and its yield was about 0.6 adduct/10(5) nucleotides.

A study of metal chelation of dinucleotide analogs in the gas phase by fast-atom bombardment mass spectrometry

Fast-atom bombardment (FAB) mass spectrometry was used to investigate the interaction of proton and alkali metal ions with dinucleotide analogs such as T-n-T (T = thymine moiety, n = polyether chain, e.g., triethylene, tetraethylene, pentaethylene, and hexaethylene ether 1-4), A-n-T (A = adenine unit 5-8), and T-n-OMe (9-12) in 3-nitrobenzyl alcohol matrix. The [M + H](+) ion is the most abundant ion for the A-n-T series, whereas in 1-4 and 9-12 the (TC2H4)(+) ion is the most abundant. Formation of [M + H -C2H4O](+) ions, a characteristic fragmentation of crown ethers under electron ionization, is observed for compounds 1-12 and is more pronounced in 6 and 7. An abundant [M - H](-) ion is observed for all the compounds studied under negative ion FAB due to the presence of the (-CO-NH-CO-) group of thymine, an indication of existence of intramolecular H bonding. The FAB mass spectra of 1-12 with alkali metal ions (Li(+), Na(+), K(+), Rb(+), and Cs(+)) showed formation of abundant metal-coordinated ions ([M + Met](+) and [TC2H4 + Met](+)). Compounds 3, 4, 6, 7, and 10-12 showed ions due to the substitution of the thymine moiety by a hydroxyl group ([M + Met - 108](+), Met = metal ion). For compound 3 alone, substitution of two thymine groups ([M + Met - 216](+)) was observed. Metastable ion studies were used to elucidate the structures of these potentially significant ions, and the ion formule were confirmed with high resolution measurements. Selectivity toward metal complexation with ligand size was seen in the T-n-T and A-n-T series and was even more pronounced in A-n-T series. These dinucleotide analogs fall in the following order of chelation of alkali metal ions, acyclic glymes < dinucleotide analogs (acyclic glymes substituted with nitrogen bases) < crown ethers, which places them in perspective as receptor models.

A new method of determination of adenine units location in DNA

A new method of determination of adenine units location in DNA

Synthesis of nucleic acid base substituted poly-L-lysine

As a new type of the nucleic acid analogs, poly-L-lysine derivatives containing adenine, thymine and uracil were prepared. By using the activated ester method, carboxyethyl derivatives of the nucleic acid bases were grafted onto poly-L-lysine. The thymine and uracil derivatives were completely substituted to poly-L-lysine. The content of adenine unit in the polymer, however, was less than that of the thymine analog.

Rates of Aziridinium Alkylation of Polynucleotides and Ribonucleic Acid

The exceptionally high rate of alkylation of guanine units in double helix DNA (k g /kw1 = 150,000) (P rice , C. C., G aucher , G. M., K oneru , P., S hibakawa , R., S owa , J. R., and Y amaguchi , M. (1968) Biochim. Biophys. Acta 166, 327) has now been observed for tRNA (k g /kw = 97,000), rRNA (k g /kw = 93,000), and a 1:1 mixture of polyguanylic and polycytidylic acid (k g /kw = 80,000). The unreactivity of adenine units in double helix DNA (1) has also been found in a 1:1 mixture of polyadenylic and polyuridylic acids. Poly(A), poly(C), and poly(G) all show markedly greater base reactivity than their monomers, ascribed partly to enhanced reactivity from stacking of the bases in the polymers. Poly(G), poly(C), tRNA, and rRNA showed sharp rate changes after 5 to 10% reaction, interpreted as due to “denaturation” or degradation resulting from alkylation of the bases and/or the phosphate groups. Very high initial reactivities (kp/kw ≃ 106) for the phosphate groups, in poly(A), (A)n·(U)n, tRNA, and rRNA, are ascribed to electrostatic effects, neutralized as alkylation proceeds.

Relative reactivities for monofunctional nitrogen mustard alkylation of nucleic acid components

Quantitative studies of alkylation of nucleic acid bases have led to values for relative nucleophilicities of their reactive centers toward the diethylethylenimonium ion. The alkylation of native, double-helix DNA by diethylethylenimonium ion for 2 h at 40° and pH 7, followed by hydrolysis, dialysis and chromatography, showed only 7-alkylated guanine. After 48 h, considerable N 6-alkylated adenine was also obtained. Since complete denaturation and extensive degradation of DNA occurred under the latter conditions, initially denatured DNA was alkylated for 2 h and found to give about equal amounts of both compounds. The alkylation of guanine in native DNA proceeded at a rate 50-fold greater and in denatured DNA at a rate 7-fold greater than in monomeric guanine ribosides and ribotides. While adenine units in native DNA are unreactive, in denatured DNA they react at a rate 5 times those in poly A.

The selective 1-N-oxidation of nucleobases in homopolynucleotides and in nucleic acids

1. 1. The 1-N-oxidation of adenine in adenosine derivatives, and the corresponding oxidation of cytosine in cytidine derivatives (other bases could not be transformed into the 1-N-oxides under conditions employed), has been applied to polynucleotides. During these reactions characteristic alterations of the ultraviolet spectra of the polynucleotides appeared. After formation of the poly-(A+U) double stranded complex a very strong inhibition of the poly-A oxidation was observed. 2. 2. The oxidation of poly-C-in comparison with poly-A-yielded smaller values for the reaction rate in the starting phase and for the degree of end-oxidation. 3. 3. During oxidation experiments with RNA and DNA, adenine as cytosine units were also oxidized. Only the oxidation degree of the adenine units was studied. Oxidation experiments with DNA showed a dependency of the reaction rate in the starting phase and of the degree of end-oxidation on the condition of the DNA (native or denatured).

Quantitative infrared spectra in D 2O of some nucleosides, nucleotides, and polynucleotides: A new measure of polynucleotide interaction

Integrated infrared absorption intensities have been determined for some nucleosides, nucleotides, and polynucleotides in D 2O solution. There are marked changes in the infrared spectra upon mixing the polynucleotides Poly A and Poly U. These changes are considered to result from hydrogen-bonding interaction between the two polynucleotides. The spectra indicate that the uracil residues in the nucleosides, nucleotides, polynucleotides, and in the mixture of polynucleotides are in the keto form and that the adenine units are probably in the amino form.