TY - JOUR
T1 - Understanding the acid-base properties of adenosine
T2 - the intrinsic basicities of N1, N3 and N7
AU - Kapinos, Larisa E.
AU - Operschall, Bert P.
AU - Larsen, Erik
AU - Sigel, Helmut
N1 - PT: J; UT: WOS:000293702500026
M1 - Journal Article
PY - 2011/7/11
Y1 - 2011/7/11
N2 - Adenosine (Ado) can accept three protons, at N1, N3, and N7, to give H 3(Ado)3+, and thus has three macro acidity constants. Unfortunately, these constants do not reflect the real basicity of the N sites due to internal repulsions, for example, between (N1)H+ and (N7)H+. However, these macroconstants are still needed for the evaluations and the first two are taken from our own earlier work, that is, pKH3(Ado)H=-4.02 and pKH2(Ado) H=-1.53; the third one was re-measured as pKH(Ado) H=3.64±0.02 (25°C; I=0.5M, NaNO3), because it is the main basis for evaluating the intrinsic basicities of N7 and N3. Previously, contradicting results had been published for the micro acidity constant of the (N7)H+ site; this constant has now been determined in an unequivocal manner, and that of the (N3)H+ site was obtained for the first time. The micro acidity constants, which describe the release of a proton from an (N)H+ site under conditions for which the other nitrogen atoms are free and do not carry a proton, decrease in the order pK N7(Ado)N1.HN7-N1=3.63±0.02 > pK H.N7(Ado)N1N7-N1=2.15±0.15 > pK H.N3(Ado)N1,N7N3-N1,N71.5±0.3, reflecting the decreasing basicity of the various nitrogen atoms, that is, N1>N7>N3. Application of the above-mentioned microconstants allows one to calculate the percentages (formation degrees) of the tautomers formed for monoprotonated adenosine, H(Ado)+, in aqueous solution; the results are 96.1, 3.2, and 0.7% for N7(Ado)N1̇H+, +ḢN7(Ado)N1, and +ḢN3(Ado)N1,N7, respectively. These results are in excellent agreement with theoretical DFT calculations. Evidently, H(Ado)+ exists to the largest part as N7(Ado)N1̇H+ having the proton located at N1; the two other tautomers are minority species, but they still form. These results are not only meaningful for adenosine itself, but are also of relevance for nucleic acids and adenine nucleotides, as they help to understand their metal ion-binding properties; these aspects are briefly discussed.
AB - Adenosine (Ado) can accept three protons, at N1, N3, and N7, to give H 3(Ado)3+, and thus has three macro acidity constants. Unfortunately, these constants do not reflect the real basicity of the N sites due to internal repulsions, for example, between (N1)H+ and (N7)H+. However, these macroconstants are still needed for the evaluations and the first two are taken from our own earlier work, that is, pKH3(Ado)H=-4.02 and pKH2(Ado) H=-1.53; the third one was re-measured as pKH(Ado) H=3.64±0.02 (25°C; I=0.5M, NaNO3), because it is the main basis for evaluating the intrinsic basicities of N7 and N3. Previously, contradicting results had been published for the micro acidity constant of the (N7)H+ site; this constant has now been determined in an unequivocal manner, and that of the (N3)H+ site was obtained for the first time. The micro acidity constants, which describe the release of a proton from an (N)H+ site under conditions for which the other nitrogen atoms are free and do not carry a proton, decrease in the order pK N7(Ado)N1.HN7-N1=3.63±0.02 > pK H.N7(Ado)N1N7-N1=2.15±0.15 > pK H.N3(Ado)N1,N7N3-N1,N71.5±0.3, reflecting the decreasing basicity of the various nitrogen atoms, that is, N1>N7>N3. Application of the above-mentioned microconstants allows one to calculate the percentages (formation degrees) of the tautomers formed for monoprotonated adenosine, H(Ado)+, in aqueous solution; the results are 96.1, 3.2, and 0.7% for N7(Ado)N1̇H+, +ḢN7(Ado)N1, and +ḢN3(Ado)N1,N7, respectively. These results are in excellent agreement with theoretical DFT calculations. Evidently, H(Ado)+ exists to the largest part as N7(Ado)N1̇H+ having the proton located at N1; the two other tautomers are minority species, but they still form. These results are not only meaningful for adenosine itself, but are also of relevance for nucleic acids and adenine nucleotides, as they help to understand their metal ion-binding properties; these aspects are briefly discussed.
U2 - 10.1002/chem.201003544
DO - 10.1002/chem.201003544
M3 - Journal article
C2 - 21626581
SN - 0947-6539
VL - 17
SP - 8156
EP - 8164
JO - Chemistry: A European Journal
JF - Chemistry: A European Journal
IS - 29
ER -