Anna Gasowska

Complexes of copper(II) with spermine and non-covalent interactions in the systems including nucleosides or nucleotides

Abstract Taking into account a change in the acid-base properties of metal-free systems of spermine (Spm) and nucleoside (Nuc) or nucleotide (NMP), appearing as a result of non-covalent interactions between the bioligands, the composition of the molecular complexes formed and their overall stability constants were determined. The centres of ion–dipole interactions were established to be protonated amine groups of Spm and the nitrogen donor atoms of nucleosides as well as the phosphate residues and the nitrogen donor atoms of nucleotides. A distinct difference was found between the behavior of adenosine monophosphate and cytidine monophosphate. The presence of at least two reaction centers in the majority of relatively stable adducts was found which emphasizes the role of spatial arrangement in the species. The assumed model of interactions is supported by the fact that molecular complex formation is observed in the pH range of nucleoside or nucleotide deprotonation and polyamine protonation. The co-ordination nature of spermine in the systems with Cu(II) differs from that of polyamines of shorter chains. The stability constants of the mixed-ligand complexes formed, their stochiometry and mode of co-ordination were determined (the main co-ordination sites are the nucleotide phosphate residues as well as N(1) and N(7) atoms of purine or N(3) of pyrimidine rings). The interactions in nucleoside-containing systems are, however, essentially different from those in the systems which comprise nucleotides. The formation of Cu(AMP)H x (Spm) and Cu(CMP)H x (Spm) adducts, in which copper ions were coordinated only via oxygen atoms of phosphate groups, was established. In the case of nucleoside-containing systems, it was found that Cu(Nuc)(Spm) mixed-ligand complexes with a chromophore of N5-type are formed.

Interactions in binary and ternary systems including Cu(II), uridine, uridine 5′-monophosphate or diamine

Abstract Results of equilibrium and spectral studies have shown that, in the systems of uridine (Urd) or uridine 5′-monophosphate (UMP) with the diamines (PA) ethylenediamine, 1,3-diaminopropane or putrescine, molecular complexes of the type (Urd)Hx(PA) and (UMP)Hx(PA) are formed. Overall stability constants of the adducts and equilibrium constants of their formation have been determined. The tendency towards complex formation increases with growing length of the PA. The pH range of adduct formation is found to coincide with that in which the PA is protonated, whereas Urd or its monophosphate is deprotonated. The NH3+ groups from PA and N(3) atoms and phosphate groups from the nucleosides have been identified as the centres of non-covalent interactions. Overall stability constants of the Cu(II) complexes with Urd and UMP have been determined. It was found that, in the Cu(Urd)+ and Cu(Urd)(OH)x complexes, the reaction of metallation mainly involves N(3) atoms from the pyrimidine bases. Results of the spectral and equilibrium studies of the Cu/UMP system indicate coordination involving the N(3) atom and the phosphate groups from UMP, whereas in the complexes Cu(UMP)(OH)x, appearing at high pH, the involvement of the N(3) atom has been excluded and the main sites of metallation are oxygen atoms from carbonyl groups, besides those from hydroxyl groups. The mode of coordination of Cu(II) complexes with Urd or UMP, including diamines, was also determined.

Copper(II) ions as a factor interfering in the interaction between bioligands in systems with adenosine and polyamines

Abstract Noncovalent interactions were found to occur in metal-free adenosine-polyamine systems. Overall stability constants and equilibrium constants of the reaction of adduct formation were determined. The ranges in which the adducts occur overlap with the ranges in which nucleoside is deprotonated while polyamine is protonated. Stability constants and complex distribution in the ternary Cu/Ado/PA (PA = polyamine) systems were also identified. The coordination mode in the studied complexes in solution was determined. Unlike in 1,3-diaminopropane (tn), putrescine (Put), and 1,7-diamino-4-azaheptane (3,3-tri), in the systems containing spermidine (Spd), the coordination dichotomy between the N(1) and N(7) atoms of nucleoside was observed to disappear. In some complexes occurring in the systems with tn, 3,3-tri (but not with Put and Spd), a coordination with nitrogen atoms at axial position was detected in solution. Generally, however, a tendency to form square-planar structures dominates. Differences in the coordination mode of complexes in solution and solid complexes were determined.

Investigations of binding sites and stability of complexes formed in ternary Cu(II)/adenosine or cytidine/putrescine systems

Abstract In the adenosine-putrescine (1,4-diaminobutane) system, noncovalent interaction between bioligands was found to occur. The equilibrium constant of the adduct formation reaction is equal to log K = 1.51. The ligand-ligand interaction is not observed to occur in the cytidine/putrescine system. On the basis of computer analysis of potentiometric titration data for ternary systems: Cu(II)/adenosine (or cytidine)/putrescine, the stability constants of the complexes were determined and their distribution was presented. It was found that in the cytidine-containing systems, mixed-ligand complexes are not formed. Spectral studies indicate characteristic differences in the mode of coordination in the adenosine ternary systems relative to binary systems. A presence of putrescine contributes to the broadening (relative to the Cu(II)/Ado binary system) of pH range for the coordination dichotomy to occur. Differences in the coordination mode between the synthesized solid complexes and complexes in solution have been identified. Likewise in solution, cytidine does not form solid mixed-ligand complexes with Cu(II) and putrescine.

Mode of coordination and stability of Cu(II) and Zn(II) complexes with adenosine, deoxyadenosine, cytidine and deoxycytidine

SummaryStability constants of Cu(II) and Zn(II) complexes with nucleosides have been determined from a computer analysis of potentiometric titration results. Spectral investigations prove that in acidic solution adenosine coordinates to Cu(II)via its N1 or N7 atoms, while atpH>7 only N7 is involved. Similar interactions are observed for dAdo complexes. Spectral and potentiometric studies suggest that Zn does not form stable complexes with dAdo. In the case of cytidine and deoxycytidine, the preferred site of coordination is the N3 atom of the nucleoside. Oxygen atoms from the carbonyl groups are not involved in Cu(II) or Zn(II) coordination. The results of the spectral investigation have excluded the ribose and deoxyribose moieties of all studied ligands from participation in the interactions. In general, the mode of coordination of nucleosides and deoxynucleosides with Cu(II) and Zn(II) has been found analogous.ZusammenfassungMittels einer Computeranalyse von Ergebnissen aus potentiometrischen Titrationen wurden Stabilitätskonstanten für Komplexe aus Cu(II) bzw. Zn(II) und Nucleosiden bestimmt. Spektroskopische Untersuchungen zeigen, daß Adenosin in saurer Lösung über N1 oder N7 an Cu(II) koordinieren kann, während beipH>7 nur N7 reagiert. Analoges wird für die Komplexe mit dAdo beobachtet. Aus spektroskopischen und potentiometrischen Untersuchungen geht hervor, daß Zn mit dAdo keine stabilen Komplexe bildet. Im Fall von Cytidin und Deoxycytidin ist N3 die bevorzugte Koordinationsstelle des Nucleosids. Die Sauerstoffatome der Carbonylgruppen sind an der Bindung an Cu(II) und Zn(II) nicht beteiligt. Die spektroskopischen Ergebnisse schließen eine Beteiligung der Ribose- und Deoxyriboseeinheiten an den Wechselwirkungen aus. Allgemein wurde für Nucleoside und Deoxynucleoside ein analoger Koordinationsmodus gefunden.

Intermolecular and coordination reactions in the systems of copper(II) with adenosine 5′-monophosphate or cytidine 5′-monophosphate and triamines

Formation of molecular complexes as a result of non-covalent interactions between adenosine 5-monophosphate (AMP) or cytidine 5-monophosphate (CMP) and polyamines, 1,5-diamino-3-azapentane (dien) or 1,6-diamino-3-azahexane (2,3-tri), has been studied in metal-free systems. Based on the acid–base equilibrium changes, the composition and stability constants of the molecular complexes formed have been determined. Spectral analysis has revealed that the interaction centers in these adducts are protonated amine groups from the polyamine, phosphate groups and donor nitrogen atoms from the nucleotide. In the ternary systems of Cu(II) with AMP or CMP and polyamines, dien or 2,3-tri, the composition and stability constants of the heteroligand complexes formed have been determined. The presence of the following complexes has been detected: Cu(CMP)(dien), Cu(AMP)(dien), Cu(CMP)(2,3-tri), Cu(CMP)(2,3-tri)(OH). Results of the equilibrium and spectral studies (Vis, IR, EPR, 13 C, 31 P NMR) have shown that in the mixed complexes, all nitrogen atoms from the polyamine and oxygen atoms from the phosphate group of the nucleotide take part in the coordination. The donor nitrogen atoms N(1) and N(7) from AMP and N(3) from CMP are in the outer coordination sphere.

Spectroscopic and potentiometric investigation of the solution structure and stability of Ni(II) and Co(II) complexes with adenosine 5′-monophosphate and 1,12-diamino-4,9-diazadodecane (spermine) or 1,11-diamino-4,8-diazaundecane

Abstract The solution structures of nickel(II) and cobalt(II) mixed-ligand complexes with adenosine 5′-monophosphate and tetramines have been found. The nickel(II) ions were proved to coordinate the nitrogen atoms N(1) and N(7) from the nucleotide forming chromophore {N1} in the molecular complexes of type ML·····L′ and chromophore {N3} in the protonated complexes. In the mixed-ligand complexes with nickel(II) ions, a coordination dichotomy N1/N7 was observed. In the mixed complexes with cobalt(II) ions, the presence of a chromophore {N1,O}, with N(7) nitrogen atom and oxygen atoms from the AMP phosphate group, was found. On the other hand, in molecular complexes the non-covalent interactions between the totally protonated polyamine and nucleotide atoms of high electron density were established. The presence of interligand non-covalent interactions, additionally stabilising the complex, was discovered in the species Ni(AMP)H2(Spm). Results of the equilibrium study for the species Ni(AMP)H2(3,3,3-tet) indicated that only one nitrogen atom from the polyamine was involved in the coordination.

Noncovalent interactions in polyamine/nucleoside (or diaminocarboxylate)systems studied by potentiometric and NMR techniques

Noncovalent interactions and formation of molecular complexes have been found to occur between a number of polyamines and adenosine or cytidine. Since these observed interactions affect the acid–base character of particular components of the systems the determination of overall stability constants of the complexes was possible on the basis of a computer analysis of potentiometric data and then equilibrium constants of the reactions were calculated. The comparison of the constants and the changes in the position of 13C NMR signals provided grounds for a conclusion that mainly two (or three) –NHx+ groups of amine and electron-rich centres as well as the system of π electrons from purine and pyrimidine bases constitute sites for the interactions. The tendency of particular polyamines to form adducts depends on the number of nitrogen atoms as well as the length of the methylene chains in the molecules. Distributions of molecular complexes as a function of pH were calculated. The ranges of the occurrence of PA/Nuc molecular complexes overlap with those of nucleoside deprotonation and polyamine protonation, which confirms the validity of the assumed model of interactions. It was found that in the polyamine systems with diaminocarboxylates no adducts were formed.

Complexes of Cu(II) Ions and Noncovalent Interactions in Systems with L-Aspartic Acid and Cytidine-5'-Monophosphate

Interactions between aspartic acid (Asp) and cytidine-5-monophosphate (CMP) in metal-free systems as well as the coordination of Cu(II) ions with the above ligands were studied. The composition and overall stability constants of the species formed in those systems were determined by the potentiometric method, and the interaction centres in the ligands were identified by the spectral methods UV-Vis, EPR, NMR, and IR. In metal-free systems, the formation of adducts, in which each ligand has both positive and negative reaction centres, was established. The main reaction centres in Asp are the oxygen atoms of carboxyl groups and the nitrogen atom of the amine group, while the main reaction centre in CMP at low pH is the N(3) atom. With increasing pH, the efficiency of the phosphate group of the nucleotide in the interactions significantly increases, and the efficiency of carboxyl groups in Asp decreases. The noncovalent reaction centres in the ligands are simultaneously the potential sites of metal-ion coordination. The mode of coordination in the complexes formed in the ternary systems was established. The sites of coordination depend clearly on the solution pH. In the molecular complexes MLcdots, three dots, centeredL, metallation involves the oxygen atoms of the carboxyl groups of the amino acid, while the protonated nucleotide is in the outer coordination sphere and interacts noncovalently with the anchoring CuH(x)(Asp) species. The influence of the metal ions on the weak interactions between the biomolecules was established.

Interactions of diamines with adenosine-5′-triphosphate (ATP) in the systems including copper(II) ions

Interactions were studied in the systems ATP/tn and ATP/Put (tn=1,3-diaminopropane, Put=putrescine) whereas the complexation reactions in ternary systems Cu(II)/ATP/tn and Cu(II)/ATP/Put. Results of the potentiometric and spectroscopic studies evidenced the formation of adducts of the type (ATP)Hx(PA), where PA=diamine. The thermodynamic stability of the complexes and the mode of interactions were determined. On the basis of analysis of changes in the positions of NMR signals, in the pH range of (ATP)H3(Put) formation, the preferred centres of the interaction between ATP and Put are the endocyclic nitrogen atoms from the nucleotide. On the other hand, the shorter diamine tn in the entire pH range reacts with the phosphate groups from ATP. The positive centres of noncovalent interactions are the protonated NHx+ groups from amines. In both complexes Cu(ATP)H2(tn) and Cu(ATP)H3(Put) formed in ternary systems at pH<6.5, the amines are in the outer sphere of coordination with the noncovalent interaction with anchoring Cu(ATP). Only the phosphate groups from the nucleotide take part in metalation. At higher pH in the range of Cu(ATP)(PA) complex formation, significant differences in the reactions of the two amines appear. The shorter one (tn) binds Cu(II) ions with two nitrogen atoms, while putrescine coordinates in the monofunctional mode, which is undoubtedly related to the differences in lengths of methylene chain. This explains the considerable differences in the stability of Cu(ATP)(tn) and Cu(ATP)(Put). In both complexes the nucleotide is coordinated through phosphate groups. SYNOPSIS As a result of noncovalent interactions ATP forms molecular complexes with 1,3-diaminopropane and 1,4-diaminobutane (putrescine). Significant differences in the mode of interactions between the two diamines were observed in ATP/diamine binary systems and in ternary systems Cu(II)/ATP/diamine, at high pH.