Bin Song

Stability of metal ion complexes formed with methyl phosphate and hydrogen phosphate

Abstractu2002The acidity constants of methyl phosphoric acid, CH3OPO(OH)2, and orthophosphoric acid, HOPO(OH)2, and the stability constants of the 1u200a:u200a1 complexes formed between Mg2+, Ca2+, Sr2+, Ba2+, Mn2+, Co2+, Ni2+, Cu2+, Zn2+, or Cd2+ and methyl phosphate, CH3OPO32–, or hydrogen phosphate, HOPO32–, were determined by potentiometric pHu2009titration in aqueous solution (25u200au200a°C;Iu2009=u20090.1u2009M, NaNO3). On the basis of previously established log K versus pKa straight-line plots for the complexes of simple phosphate monoesters and phosphonate derivatives, R-PO32–, where R is a noncoordinating residue, it is shown that the stability of the M(CH3OPO3) complexes is solely determined (as one might expect) by the basicity of the –PO32– residue. It is emphasized that the mentioned reference lines may also be used to reveal increased complex stabilities, for example, for certain complexes formed with 8-quinolyl phosphate the occurrence of 7-membered chelates can be proven in this way; the same procedure is also applicable to complexes of nucleotides, etc. The M(HOPO3) complexes are slightly more stable (on average by 0.08 log unit) than it is expected from the basicity of HPO42–; this observation is attributed to a more effective solvation, including hydrogen bonding, than is possible with CH3OPO32– species.

Metal ion-coordinating properties of imidazole and derivatives in aqueous solution: interrelation between complex stability and ligand basicity

Abstract The stability constants of the 1:1 complexes formed between Mg2+, Ca2+, Sr2+, Ba2+, Mn2+, Co2+, Ni2+, Cu2+, Zn2+ or Cd2+ (M2+) and the simple, sterically unhindered imidazole-type ligands, imidazole, 1-methylimidazole, 5-chloro-1-methylimidazole, N-(2,3,5,6-tetrafluorophenyl)imidazole or 4′-(imidazol-1-yl)acetophenone (L), were determined by potentiometric pH titrations in aqueous solution (25°C; I = 0.5 M, NaNO3). The construction of log KMLM versus pKHLH plots results in straight lines; the equations for the least-squares lines are calculated and listed. These data allow calculation of the expected stability constant for a complex of any imidazole-type ligand, provided its pKHLH value (in the pKa range 4–8) is known. For the stabilities of Fe2+ complexes with imidazole-type ligands an estimation procedure is provided. It is shown further that the complex formation between 1-methylbenzimidazole (MBI) and Mn2+, Ni2+, Cu2+ or Zn2+ is s sterically hindered, i.e. the data points for these M(MBI)2+ complexes do not fall on the straight lines defined by the imidazole-type ligands.

Intramolecular stacking interactions in mixed ligand complexes formed by copper(II), 2,2′-bipyridine or 1,10-phenanthroline, and monoprotonated or deprotonated adenosine 5′-diphosphate (ADP3−). Evaluation of isomeric equilibria☆

Abstract The stability constants of the 1:1 complexes formed between Cu 2+ or Cu(Arm) 2+ , where Arm=2,2′-bipyridine (Bpy) or 1,10-phenanthroline (Phen), and adenosine 5′-diphosphate (ADP 3− ) or its monoprotonated form H(ADP) 2− were determined by potentiometric pH titrations in aqueous solution (25°C; I =0.1 M, NaNO 3 ). It is shown that the stability of the binary Cu(ADP) − complex is enhanced due to macrochelate formation of the diphosphate-coordinated metal ion with N7 of the adenine residue. Such a macrochelate is also formed in the monoprotonated Cu(H;ADP) complex in which the proton is at the terminal β-phosphate group. The latter is also true for the ternary Cu(Arm)(H;ADP) species, but here intramolecular stacks are formed between the aromatic rings of Arm and the adenine moiety. The isomeric equilibria of both protonated complexes are evaluated. The enhanced stability of about 0.7–0.8xa0log units of the Cu(Arm)(ADP) complexes is clearly attributable to intramolecular stack formation; indeed, the corresponding isomer occurs to about 80% being in equilibrium with the open, unstacked form. Comparison of the stacking tendencies observed for a series of Cu(Arm)(N) complexes, where N=AMP 2− , ADP 3− and ATP 4− (adenosine 5′-mono-, di-, or triphosphate) or UMP 2− , UDP 3− or UTP 4− (uridine 5′-mono-, di-, or triphosphate), reveals that the extent of intramolecular stack formation in the complexes does not depend significantly on the length of the phosphate residue but rather on the size of the nucleobase, i.e. one ring (uracil) versus two rings (adenine). Roughly speaking, the formation degree of the intramolecular stacks in the ternary complexes containing the uracil residue amounts to about 50% (corresponding to a stability increase of about 0.3 log units) whereas in the corresponding adenine complexes about 80–90% (corresponding to a stability enhancement of approximately 0.8–1xa0log units) are reached; the relevance of this kind of adduct formation for recognition reactions in nature is evident.

Ternary complexes in solution. Intramolecular stacking interactions in mixed ligand complexes formed by copper(II), 2,2′-bipyridyl or 1,10-phenanthroline and a pyrimidine-nucleoside 5′-diphosphate (CDP3−, UDP3−, dTDP3−)

Abstract The stability constants of the 1:1 complexes formed between Cu 2+ or Cu(Arm) 2+ , where Arm = 2,2′-bipyridyl (Bpy) or 1,10-phenanthroline (Phen), and pyrimidine-nucleoside 5′-diphosphates (NDP 3− , i.e. CDP 3− , UDP 3− or dTDP 3− ), were determined by potentiometric pH titrations in aqueous solution (25°C; I = 0.1 M, NaNO 3 ). It is shown that the stability of the binary Cu(NDP) − complexes is determined solely by the basicity of the diphosphate group; this is different for the ternary Cu(Arm)(NDP) − complexes. It is demonstrated that the equilibrium, Cu(Arm) 2+ + Cu(NDP) − Cu(Arm)(NDP) − + Cu 2+ , is displaced considerably to the right-hand side. Part of this displacement is due to the well known experience that mixed ligand complexes formed by a divalent 3d ion, a heteroaromatic N base and an O donor ligand possess increased stability. This increased stability is now accounted for by the results obtained recently for the Cu 2+ /Arm/methylphosphonylphosphate (CH 3 -P(O) 2 − -O-PO 3 2− ) systems (B. Song et al., Inorg. Chim. Acta, 273 (1998) 101). The other part of this displacement, which amounts on average to an increased stability of the mixed ligand Cu(Arm)(NDP) − complexes of about 0.35 log unit, is due to an intramolecular ligand—ligand stacking between the nucleobase residues and the aromatic rings of Bpy or Phen. The formation degree of these intramolecular stacks in the Cu(Arm)(NDP) − complexes corresponds to approximately 55%, thus leaving about 45% of the complexes in an unstacked or open form in this intramolecular isomeric equilibrium. The relevance of the results regarding biological systems is indicated briefly.

Acid-base and metal ion-binding properties of 2′-deoxycytidine 5′-monophosphate (dCMP2−) alone and coordinated to cis-diammine-platinum(II). Formation of mixed metal ion nucleotide complexes

Abstract The acidity constants of diprotonated 2′-deoxycytidine 5′-monophosphate, i.e. H 2 (dCMP) ± , were determined by potentiometric pH titration in aqueous solution (25 °C; I = 0.1 M, NaNO 3 ) and compared with the previously determined (S.S. Massoud and H. Sigel, Inorg. Chem., 27 (1988) 1447–1453) corresponding constants of diprotonated cytidine 5′-monophosphate, i.e. H 2 (CMP) ± . The absence of the 2′-hydroxy group makes dCMP 2− slightly more basic, compared with CMP 2− . The stability constants of the M(H·dCMP) + and M(dCMP) complexes of Mg 2+ , Cu 2+ and Zn 2+ were determined and those for the corresponding CMP complexes reevaluated. It is concluded that in the M(H·dCMP) + and M(H·CMP) + species the metal ion is mainly located at N-3 and the proton at the phosphate group. On the basis of recent measurements with simple phosphate monoesters and phosphonate derivatives, i.e. R-PO 3 2− with R being a non-coordinating residue (H. Sigel et al., Helv. Chim. Acta, 75 (1992) 2634–2656), it is shown that the stability of all the M(dCMP) and M(CMP) complexes is solely determined by the basicity of the phosphate group. Coordination of two H(dCMP) − ions via N-3 to cis -(NH 3 ) 2 Pt 2+ gives H 2 [ cis -(NH 3 ) 2 Pt(dCMP) 2 ], abbreviated as H 2 (Pt(dC) 2 ), the synthesis of which is described and the acidity constants of which were determined. Pt 2+ bound to the N-3 sites apparently has only a small effect on the basicity of the two phosphate groups in Pt(dC) 2 2− . In addition, also via pitentiometric pH titrations, the stability constants of the M(H·Pt(dC) 2 ) + and M(Pt(dC) 2 ) complexes with Mg 2+ , Cu 2+ and Zn 2+ were determined. Based on the previously determined (see the above Ref.) linear log K M(R−PO 3 ) M versus p K H(R-PO 3 ) H relationships it is shown that the metal ion-binding properties of the phosphate groups in the mentioned platinum(II) complex are still remarkable, allowing thus the formation of mixed metal ion complexes. In fact, the effect of Pt 2+ at the N-3 sites on the binding properties of the phosphate groups is relatively small; to a first approximation, though there are some minor additional effects, one may conclude that also in these cases the complex stabilities are mainly determined by the basicity of the phosphate groups.

Ternary complexes in solution1 with hydrogen phosphate and methyl phosphate as ligands

Abstract The stability constants of the 1:1 complexes formed between Cu(Arm) 2+ , where Arm = 2,2′-bipyridyl or 1,10-phenanthroline, and methyl phosphate, CH 3 OPO 3 2− , or hydrogen phosphate, HOPO 3 2− , were determined by potentiometric pH titration in aqueous solution (25°C; l = 0.1 M, NaNO 3 ). On the basis of previously established log K versus p K a straight-line plots (D. Chen et al., J. Chem. Soc., Dalton Trans. (1993) 1537–1546) for the complexes of simple phosphate monoesters and phosphonate derivatives, R-PO 3 2− , where R is a non-coordinating residue, it is shown that the stabilities of the Cu(Arm) (CH 3 OPO 3 ) complexes are solely determined by the basicity of the -PO 3 2− residue. In contrast, the Cu(Arm) (HOPO 3 ) complexes are slightly more stable (on average by 0.15 log unit) than expected on the basicity of HPO 4 2− ; this is possibly due to a more effective solvation including hydrogen bonding, an interaction not possible with coordinated CH 3 OPO 3 2− species. Regarding biological systems the observation that HOPO 3 2− is somewhat favored over R-PO 3 2− species in metal ion interactions is meaningful.

Evidence for intramolecular aromatic-ring stacking in the physiological pH range of the monodeprotonated xanthine residue in mixed-ligand complexes containing xanthosinate 5′-monophosphate (XMP)

The stability constants of the mixed-ligand complexes formed between Cu(Arm)2+ [Arm = 2,2-bipyridine (Bpy) or 1,10-phenanthroline (Phen)], and the di- or trianion of xanthosine 5-monophosphoric acid [= XMP(2-) or (XMP - H)(3-)] were determined by potentiometric pH titration in aqueous solution (25 degrees C; I = 0.1 M, NaNO3). Those for the monoanion, i.e., the Cu(Arm)(H;XMP)+ complexes, could only be estimated; for these species it is concluded that the metal ion is overwhelmingly bound at N7 and the proton resides at the phosphate group. Similarly, in the Cu(Arm)(XMP)+/- [= Cu(Arm)(X - H.MP.H)+/-] complexes Cu(Arm)2+ is also at N7 but the xanthine residue has lost a proton whereas the phosphate group still carries one, i.e., stacking plays, if at all, only a very minor role, yet, the N7-bound Cu(Arm)2+ appears to form an outer-sphere macrochelate with P(O)2(OH)-, its formation degree being about 60%. All this is different in the Cu(Arm)(XMP - H)- complexes, which are formed by the (XMP - H)(3-) species, that occur at the physiological pH of 7.5 and for which previously evidence has been provided that in a tautomeric equilibrium the xanthine moiety loses a proton either from (N1)H or (N3)H. In Cu(Arm)(XMP - H)- the phosphate group is the primary binding site for Cu(Arm)2+ and the observed increased complex stability is mainly due to intramolecular stack (st) formation between the aromatic-ring systems of Phen or Bpy and the monodeprotonated xanthine residue of (XMP - H)(3-); e.g., the stacked Cu(Phen)(XMP - H) isomer occurs with approximately 76%. Regarding biological systems the most important result is that at physiological pH the xanthine moiety has lost a proton from the (N1)H/(N3)H sites forming (XMP - H)(3-) and that its anionic xanthinate residue is able to undergo aromatic-ring stacking.

Stability of binary and ternary copper(II) complexes of the diphosphate analogue, methylphosphonylphosphate, in aqueous solution

Abstract The stability constants of the 1:1 complexes formed between Cu 2+ or Cu(Arm) 2+ , where Arm = 2,2′-bipyridyl or 1,10-phenanthroline, and methylphosphonylphosphate (MePP 3− ), CH 3 -P(O) 2 − -O-PO 3 2 , were determined by potentiometric pH titration in aqueous solution (25°C; I = 0.1 M, NaNO 3 ). It is shown that the equilibrium, Cu(Arm) 2+ + Cu(MePP) − Cu(Arm)(MePP) − + Cu 2+ , is considerably displaced to its right-hand side, i.e. Δ log K = log K Cu(Arm)(MePP) Cu(Arm) − log K Cu(MePP) Cu ≅ 0.45. This value is significantly larger than the estimate based on statistical considerations, i.e. Δ log K Cu/statis ≅ −0.9, but it agrees with previous observations made for mixed ligand complexes formed by a divalent transition metal ion, a heteroaromatic N base and an O donor ligand. These results will now allow evaluation of complex stabilities of corresponding complexes formed with nucleoside diphosphates.

Acid-base and metal ion-binding properties of flavin mononucleotide (FMN2−). Is a ‘dielectric’ effect responsible for the increased complex stability?

Abstract Due to contradictions in the literature we have redetermined the acid-base properties of riboflavin (ue5fbRiFl; vitamin B2), i.e. 7,8-dimethyl-10-ribityl-isoalloxazine, and of flavin mononucleotide (FMN2−), also known as riboflavin 5′-phosphate, via potentiometric pH titrations (I = 0.1 M, NaNO3; 25 °C). In contrast to various claims, the isoalloxazine ring cannot be protonated at pH > 1, a result in agreement with an early study (pKa = −0.2; L. Michaelis, M.P. Schubert and C.V. Smythe, J. Biol. Chem., 116 (1936) 587–607); deprotonation of the ring system occurs in both compounds with p K a ⋍ 10 . The pKa value of ∼ 0.7 determined for the deprotonation of H2(FMN) must be attributed to the release of the first proton from the fully protonated phosphate group; its second proton is released with pKa = 6.18 in agreement with the acidity constants of various other monoprotonated monophosphate esters. The stability constants of the 1:1 complexes formed between Mg2+, Ca2+, Sr2+, Ba2+, Mn2+, Co2+, Ni2+, Cu2+, Zn2+ or Cd2+ (ue5f8M2+) and FMN2− were determined by potentiometric pH titrations in aqueous solution (I = 0.1 M, NaNO3; 25 °C). The log stability constants of all these M(FMN) complexes are about 0.2 log units higher than expected from the basicity of the phosphate group. This slight stability increase cannot be attributed to the formation of a seven-membered chelate involving the ribit-hydroxy group at C-4′ as the stability constants for the M2+ 1:1 complexes of glycerol 1-phosphate (G1P2−) demonstrate: G1P2− contains the same structural unit which would also allow in this case the formation of the mentioned seven-membered chelate; however, the stability of the M(G1P) complexes is solely determined by the basicity of the phosphate group. Hence, in agreement with earlier conclusions (J. Bidwell, J. Thomas and J. Stuehr, J. Am. Chem. Soc., 108 (1986) 820–825) regarding Ni(FMN) one must conclude that the slight stability increase of the M(FMN) complexes has to be attributed to the isoalloxazine ring. The equality of the stability increase of the complexes for all the mentioned ten metal ions precludes its attribution to an interaction with an N site and makes a specific interaction with an O site also somewhat unlikely. In addition, carbonyl oxygens appear as not very favorable for the formation of macrochelates by a further interaction with already phosphate-coordinated metal ions. Therefore, we propose that the slight but significant stability increase originates from M(FMN) species (with a formation degree of about 30%) in which the hydrophobic flavin residue is close to the metal ion, thereby lowering the ‘effective’ dielectric constant in the microenvironment of the metal ion and thus indirectly promoting the −PO32−/M2+ interaction.

Intramolecular chelate formation involving the carbonyl oxygen of acetyl phosphate or acetonylphosphonate in mixed ligand copper(II) complexes containing also 2,2′-bipyridine or 1,10-phenanthroline. A decreased solvent polarity favours the metal ion–carbonyl oxygen recognition

The stability constants of the mixed ligand complexes formed by Cu2+, 2,2′-bipyridine or 1,10-phenanthroline (=xa0Arm) and acetyl phosphate (AcP2−) or acetonylphosphonate (AnP2−) were determined by potentiometric pH titrations in water and in water containing 30 or 50% (v/v) 1,4-dioxane (25xa0°C; Ixa0=xa00.1 M, NaNO3). Previous measurements with simple phosph(on)ate ligands, R-PO2−3 (R being a non-interacting residue), had established log KCu(Arm)Cu(Arm)(R-PO3)versus pKHH(R-PO3) straight-line plots and these were used now to prove that the Cu(Arm)(AcP) and Cu(Arm)(AnP) complexes possess a higher stability than is expected for a sole phosph(on)ate–Cu2+ coordination. This increased stability is attributed to the formation of six-membered chelates involving the carbonyl oxygen present in AcP2− and AnP2−. The formation degree of the six-membered chelates in the Cu(AcP), Cu(Bpy)(AcP), and Cu(Phen)(AcP) systems is very close to 75% in all three cases. For the corresponding systems with AnP2− it is shown that increasing amounts of 1,4-dioxane added to aqueous solutions favour the formation of the six-membered chelates in both the binary and the ternary complexes. It is concluded with regard to biological systems that such six-membered chelates will also be formed in mixed ligand complexes of other metal ions and that their formation degree will also be favoured by a reduced solvent polarity; both points are relevant for the situation in active-site cavities of enzymes.