Thymine metal complexes

Base-pairing interactions have been realized in metal complexes by extending ligand functionalization to include two complementary nucleobases (136). Sequential alkylation of 1,2-dithioethane using 2-chloroethyl-9-adenine and 3-chloropropyl-l-thymine yields the AT-... 

The stability constants of zinc(n) complexes of uracil, thymine, and cytosine have been reported.249 At 45 °C in 0.1M-KNO3, 1 1 complexes are formed. The 2 1 ligand metal complexes formed between thiosalicylic acid and zinc(n), mercury(n), cadmium-(n) and lead(n) have been isolated, and formation of the 1 1 complexes in solution has been characterized by pH-titration.250 With mercury, the 2 1 complex has been assigned the structure (7), while the other metals form complexes of general structure (8). This is thought to be a consequence of the order S—M11 bond strength being Hg > Zn > Cd > Pb. 

When a metal complex is formed with the nucleic acid base of single-stranded DNA (ssDNA), such ssDNA can be used as an alternative electrochemically-active DNA-binding ligand. For example, Palecek and coworkers reported the formation of a reversible redox-active metal complex by the reaction of osmium tetraoxide-pyridine with the thymine (T) base of ssDNA, and they developed an electrochemical gene detection method based on this modified oligonucleotide as a DNA probe [3]. 

Another metal complex which may be mentioned here is platinum-thymine blue (see Chapter 4), which, because of its mixed-valent nature, may well involve reduction in its as yet undefined mechanism of sensitizing action [45]. 

Table XIX contains stability constants for complexes of Ca2+ and of several other M2+ ions with a selection of phosphonate and nucleotide ligands (681,687-695). There is considerably more published information, especially on ATP (and, to a lesser extent, ADP and AMP) complexes at various pHs, ionic strengths, and temperatures (229,696,697), and on phosphonates (688) and bisphosphonates (688,698). The metal-ion binding properties of cytidine have been considered in detail in relation to stability constant determinations for its Ca2+ complex and complexes of seven other M2+ cations (232), and for ternary M21 -cytidine-amino acid and -oxalate complexes (699). Stability constant data for Ca2+ complexes of the nucleosides cytidine and uridine, the nucleoside bases adenine, cytosine, uracil, and thymine, and the 5 -monophosphates of adenosine, cytidine, thymidine, and uridine, have been listed along with values for analogous complexes of a wide range of other metal ions (700). Unfortunately comparisons are sometimes precluded by significant differences in experimental conditions.

The Mg+ complexes of cytosine, thymine and uracil are the most complex system studied via photodissociation spectroscopy to date . A complication for these systems is that these nucleobases can exist in various tautomeric forms and that complexation of a metal can change the stability order of the tautomers. DFT calculations located four tautomeric Mg(cytosine)+ complexes, and three of these (29, 30, and 31) were suggested to be responsible for the four reactive photofragment ions 32-35 observed at a wavelength of 360 nm (Scheme 4) . Related photofragmentation reactions were observed for the Mg(thymine)+" and Mg(uracil)+" complexes . ... 

The binding mode of uracils and thymines in neutral and deprotonated forms has been reviewed up to 1987 [13]. They coordinate hard, and relatively few soft metal ions, through 0(4) (preferentially) and 0(2). Uracil (thymine) behaves as a weak dibasic acid in alkaline media with the more basic site N(3) at pKa 9.69 (10.16), as compared to N(l) at pKa 14.2. At high pH the monoanions of uracil and thymine bind the metal ions preferentially via N(l). However, the N(3) linkage isomer of the Ptn complex has also been obtained [24]. The relatively few examples of complexes with soft metal ions, containing monodentate uracilate anions, are due to the high tendency of the ligand to bind additional metal ions to form polynuclear species [13]. 

The existence of metal intermediate complexes with deoxynucleotides has been elucidated by Eichhorn et al. (26). Proton NMR spectra of dAMP, dCMP, dGMP and dTMP show, especially for dAMP and dGMP, a strong reaction of Cu2+, although the interaction with the pyrimidines was markedly reduced. Further experiments employing 31P NMR spectroscopy show the broadening of the phosphate resonance of the deoxyribonucleotides of adenine and thymine (26). 

The relative rates of reaction of the nucleic acid bases with heavy transition metal ions at neutral pH are in the same order as the relative nucleophilicites of the bases, that is G > A > C > U or T. This order parallels the relative rates of reactions for cA-[(NH3)2Pt(OH2)2] (see Figure 9), while the equilibrium constants for the same reactions are very close in magnitude. In contrast, HsCHgOH, which is more labile to substitution, nndergoes more favorable binding with deprotonation at N-3 of thymine residues in nucleic acids. Thus the relative facilities of individual reactions can lead to differences in initial product formation (kinetic control). Subsequent changes in the metal-nucleic acid complexes can be nnder kinetic or thermodynamic control. 

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