title: Acid-base and metal ion binding properties of 2-thiocytidine in aqueous solution.
abstract: The thionucleoside 2-thiocytidine (C2S) occurs in nature in transfer RNAs; it receives attention in diverse fields like drug research and nanotechnology. By potentiometric pH titrations we measured the acidity constants of H(C2S)(+) and the stability constants of the M(C2S)(2+) and M(C2S-H)(+) complexes (M(2+) = Zn(2+), Cd(2+)), and we compared these results with those obtained previously for its parent nucleoside, cytidine (Cyd). Replacement of the (C2)=O unit by (C2)=S facilitates the release of the proton from (N3)H(+) in H(C2S)(+) (pK (a) = 3.44) somewhat, compared with H(Cyd)(+) (pK (a) = 4.24). This moderate effect of about 0.8 pK units contrasts with the strong acidification of about 4 pK units of the (C4)NH(2) group in C2S (pK (a) = 12.65) compared with Cyd (pK (a) approximately 16.7); the reason for this result is that the amino-thione tautomer, which dominates for the neutral C2S molecule, is transformed upon deprotonation into the imino-thioate form with the negative charge largely located on the sulfur. In the M(C2S)(2+) complexes the (C2)S group is the primary binding site rather than N3 as is the case in the M(Cyd)(2+) complexes, though owing to chelate formation N3 is to some extent still involved in metal ion binding. Similarly, in the Zn(C2S-H)(+) and Cd(C2S-H)(+) complexes the main metal ion binding site is the (C2)S(-) unit (formation degree above 99.99% compared with that of N3). However, again a large degree of chelate formation with N3 must be surmised for the M(C2S-H)(+) species in accord with previous solid-state studies of related ligands. Upon metal ion binding, the deprotonation of the (C4)NH(2) group (pK (a) = 12.65) is dramatically acidified (pK (a) approximately 3), confirming the very high stability of the M(C2S-H)(+) complexes. To conclude, the hydrogen-bonding and metal ion complex forming capabilities of C2S differ strongly from those of its parent Cyd; this must have consequences for the properties of those RNAs which contain this thionucleoside.
authors.affiliation: Department of Inorganic Chemistry, Wroclaw Medical University, Szewska 38, 50-139, Wroclaw, Poland. jbrasun@chnorg.am.wroc.pl
authors.forename: Justyna
authors.initials: J
authors.lastname: Brasuń
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Matera
authors.forename: Elzbieta
authors.initials: E
authors.lastname: Sochacka
authors.forename: Jolanta
authors.initials: J
authors.lastname: Swiatek-Kozlowska
authors.forename: Henryk
authors.initials: H
authors.lastname: Kozlowski
authors.forename: Bert P
authors.initials: BP
authors.lastname: Operschall
authors.forename: Helmut
authors.initials: H
authors.lastname: Sigel
mesh_terms: D000143:Acids; D002104:Cadmium / Q000737:chemistry; D003562:Cytidine / Q000031:analogs & derivatives* / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D008670:Metals / Q000737:chemistry*; D011199:Potentiometry; D012996:Solutions; D014867:Water; D015032:Zinc / Q000737:chemistry
chemical_list: D000143:Acids; D008670:Metals; D012996:Solutions; D002104:Cadmium; D014867:Water; C002908:2-thiocytidine; D003562:Cytidine; D015032:Zinc