Romualda Bregier-Jarzebowska

Coordination Reactions and Noncovalent Interactions of Polyamines with Nucleotides in Binary Systems and with Nucleotides and Copper(II) Ion in Ternary Systems

Interactions of nucleotides (AMP, CMP) and 1,2-diaminopropane (tn-1) or 2-methyl-1,2-diaminopropane (tn-2) in metal-free systems as well as in the systems including copper(II) ions were studied. The composition and overall stability constants of the complexes formed were determined by the potentiometric method, whereas the interaction centres and coordination sites were identified by spectroscopic methods. It was found that phosphate groups of nucleotides and the protonated amine groups of polyamines are the centres of interaction. The differences in the interactions with the polyamines which act as models of biogenic amines are impacted by the presence of lateral chains (methylene groups) in tn-1 and tn-2. In the ternary systems with Cu(II) ions, the heteroligand complexes are mainly of the ML⋯L type, in which the protonated polyamine is engaged in noncovalent interactions with the anchoring Cu(II)-nucleotide complex. The complexes formed in the Cu/NMP)/tn-1 system are more stable than those formed in the system with tn-2. The mode of coordination in the complex is realised mainly through the phosphate groups of the nucleotide with involvement of the endocyclic nitrogen atoms in a manner which depends upon the steric conditions and in particular on the number of the methylene groups in the polyamine molecule.

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.

Crystal and molecular structures of cadmium(II) nitrate complexes with triamines: 1,5-diamino-3-azapentane, 1,6-diamino-3-azahexane and 1,7-diamino-4-azaheptane

The following new complexes of Cd(II) nitrate with triamines have been prepared and characterized: [Cd(NH 2 (CH 2 ) 2 NH(CH 2 ) 2 NH 2 ) 2 ](NO 3 ) 2 ( 1 ), [Cd(NH 2 (CH 2 ) 2 NH(CH 2 ) 3 NH 2 ) 2 ](NO 3 ) 2 ( 2 ) and [Cd(NH 2 (CH 2 ) 3 NH(CH 2 ) 3 NH 2 ) 2 ](NO 3 ) 2 ( 3 ). Their structures have been determined by a single-crystal X-ray diffraction method. Because of the instability of the crystals 2 and 3 at room temperature, all complexes were examined at 100 K. In the complexes investigated all nitrogen atoms of the triamines coordinate the Cd(II) atom. All data sets showed {N6}-coordinated complexes. The stoichiometry of the complexes in the solid state is always 1:2, although the crystals were grown from solutions with different concentration ratios of the components (Cd–triamine: 1:1, 1:2 or 1:3). The Cd(II) atom of complex 1 is sandwiched between two triamines related by a twofold axis. Complexes 2 and 3 are characterized by a distorted octahedral coordination. The conclusions obtained correspond to the solution structures obtained from NMR, IR as well as equilibrium studies.

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.

Complexes of copper(II) with L-aspartic acid in systems with tetramines and non-covalent interactions between bioligands

In metal-free systems, interactions were studied between L-aspartic acid (Asp) and the tetramines 1,11-diamino-4,8-diazaundecane (3,3,3-tet) and 1,12-diamino-4,9-diazadodecane, spermine (Spm), and in the systems of both ligands with Cu(II). The formation of molecular complexes of the (Asp)H x (tetramine) type was evidenced by results from equilibrium and spectral studies. An increase in the efficiency of the reaction between the bioligands was observed with the increasing length of the polyamine chain. For aspartic acid, the centers of interaction are carboxyl and amine groups, whereas in tetramine molecules it is the amine groups. The effect of inversion was observed in the adducts (Asp)H4(tetramine) and (Asp)H3(tetramine). In ternary systems, the presence of molecular complexes of ML L′, protonated complexes MLH x L′, complexes MLL′, and hydroxo complexes of the MLL′(OH) x type were found, which were not detected in earlier systems with di- and triamines. In ML L′ complexes, where Lu2009=u2009L-aspartic acid and L′u2009=u2009polyamine, metallation involves the oxygens of carboxyl and amine of the amino acid, while the protonated tetramine is in the external coordination sphere, engaged in noncovalent interaction with the anchoring Cu(Asp). Moreover, in Cu(II)–Asp-tetramine in protonated species, noncovalent bonds were found between ligands which additionally stabilized the complex. At higher pH, hydroxyl groups were more effective in metallation than carboxyl groups from aspartic acid.

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.nnnSYNOPSISnAs 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.

Potentiometric and spectral studies of complex formation in the Cu(II), 3',5'-cyclic adenosine monophosphate, and tetramine systems

Reactions in the systems composed of copper(II), 3′,5′-cyclic adenosine monophosphate (cAMP), and tetramines (PA) were studied. On the basis of potentiometric and spectroscopic data in metal-free systems, formation of molecular complexes (cAMP)Hx(PA), xu2009=u20092–4, was found. Stabilities of the complexes were determined and their centers of interactions were identified. In Cu(II)/cAMP, formation of Cu(cAMP) and Cu(cAMP)(OH) was observed, with the phosphate as the main site of metallation, while in ternary systems, formation of Cu(cAMP)H4(Spm) and Cu(cAMP)(3,3,3-tet) was established. Characteristic differences in the coordination character of tetramines were found. In the Cu(II)/cAMP/Spm system, oxygens from the nucleotide phosphate are involved in metallation and protonated amines are engaged in noncovalent interaction with endocyclic nitrogens of nucleoside. In the Cu(II)/cAMP/3,3,3-tet system, a MLL′ complex is formed in which the inner coordination sphere includes polyamine nitrogens as well as the nucleotide phosphate.

Cadmium(II) and Mercury(II) Complexes in Ternary Systems with Cytidine and Diamines or Triamines

The mode of coordination of complexes formed in the systems Cd(II) or Hg(II)/cytidine/di- or triamine is proposed on the basis of equilibrium and spectroscopic studies. Mercury(II) binds much more strongly to cytidine and polyamine (PA) than cadmium. It was found from equilibrium and 13 C NMR studies that in the Hg(II) and Cd(II)/ Cyd /di- or triamine complexes, metallation mainly involves the N(3) atom of the pyrimidine base of the nucleoside and m NH x + groups from PA. In MLL complexes of both metals with diamines, all available donor nitrogen atoms of the polyamine are involved in coordination. In analogous systems with triamines, interaction of all nitrogen atoms is observed for Cd(II) systems as well as in the Hg( Cyd )(2,3- tri ) species. Only two nitrogen atoms of the polyamine coordinate in ternary Hg(II) complexes with dien, 3,3-tri and Spd .

Interactions of histone amino acid: lysine with copper(II) ions and adenosine 5′-triphosphate as well as in a metal-free system

Thermodynamic stability and mode of coordination were studied in the binary system of copper(II)/lysine, ternary system of copper(II)/ATP/lysine, and compared to the intermolecular interaction in the metal-free ATP/lysine system. In the system ATP/Lys, groups Pβ and Pγ from ATP, participate in the interaction with the amino acid, while group Pα from ATP is involved as reaction center only at high pH. The endocyclic nitrogens from the nucleotide N(1) and N(7) take part in the interactions only below physiological pH. In the binary complexes, oxygens from carboxylic group and nitrogen from the α-NH2 amino group are involved in coordination. However, introduction of the second ligand, ATP, into the system Cu(II)/Lys changes the amino acid coordination in alkaline medium. In protonated mixed-ligand complexes, the α, β, and γ oxygens of the phosphate from ATP coordinate, but at higher pH, only α oxygens coordinate in Cu(ATP)(Lys). Although Cu(II) ions do not coordinate nitrogen from ATP in the ternary system, the presence of metal ions excludes interaction of these atoms over the whole pH range studied. Graphical Abstract

Interactions of cadmium(II) ions with adenosine as well as adenosine-5′-monophosphate and diamine or triamines in the ternary systems

The mode of coordination in complexes formed in the systems Cd(II)/Ado/di- or triamine and Cd(II)/AMP/di- or triamine has been established on the basis of the equilibrium and spectral investigation. The overall stability constants (logu2009β) and equilibrium constants of formation (logu2009K e) of the complexes formed in the above systems have been determined. In the species, the main interaction centres are the nitrogen atoms N(1) or N(7) of the purine ring of Ado and AMP, while in the nucleotide also the oxygen atoms of the phosphate group and donor nitrogen atoms of the polyamine (PA) molecule. The effect of polyamine on the coordination dichotomy has been ascertained. For example, the presence of polyamine in the ternary system is responsible for involvement of only N(7) of the nucleoside in the metallation in Cd(Ado)H(Put), while in the binary system Cd(II)/Ado, the N(1)/N(7) dichotomy occurs in the whole pH range studied. Polyamine can also affect the character of the phosphate group of the nucleotide. The phosphate group, inactive in the binary system Cd(II)/AMP, after introduction of the polyamine becomes engaged in the interactions, e.g. in the complex Cd(AMP)H(dien). In Cd(AMP)H(en) and Cd(AMP)H(Put) no participation of the oxygen atom of the phosphate group has been found. This group is involved in weak interactions with a protonated amine group PA located in the outer coordination sphere. On the other hand, in the Cd(AMP)H(3,3-tri) complex the phosphate group is the only site of Cd(II) bonding. In this species the donor nitrogen atoms N(1) and N(7) of the nucleotide are outside the inner coordination sphere and involved in noncovalent interactions with protonated amine group from 3,3-tri.