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Metal-free systems of glutamic acid (Glu) with 3,3,3-tet or spermine (Spm) and ternary systems of Cu(II) ions with Glu and 3,3,3-tet or Spm were studied using the potentiometric and spectral methods: Vis, NMR and EPR. The composition, stability and mode of interaction in the formed (Glu)Hx(PA) and Cu(Glu)Hx(PA) species were established. Biogenic spermine interacts with Glu in a different way to its homologue 3,3,3-tet. In ternary systems Cu(II)/Glu/Spm, metallation involves all available nitrogen atoms from Spm, while in the form Cu(Glu)(3,3,3-tet) the uncoordinated –NH2 group species 3,3,3-tet can create a centre for potential interaction with other bioligands. In glassy state at 77 K EPR shows that only stable CuL2 type complexes exist with an axial symmetry. The geometrical structure of the complexes is discussed in the light of the results of alteration in complex structure when dynamic equilibrium at room temperature is changed during freezing. In this paper we have also quantitatively calculated how the change in the concentration of Cu(II) affects the level of molecular complexes. It was found that the introduction of Cu(II) into the studied binary ligand/ligand systems results in changes in the concentration of the molecular complexes in aqueous solution.

The mode of interaction and thermodynamic stability of complexes formed in binary and ternary Cu(II)/ATP/triamines systems were studied using potentiometric and spectroscopic (NMR, EPR, UV-Vis) methods. It was found that in binary metal-free systems ATP/HxPA species are formed (PA: Spd=spermidine or 3,3-tri=1,7-diamino-4-azaheptane) where the phosphate groups from nucleotides are preferred negative centers and protonated amine groups of amines are positive centers of reaction. In the ternary systems Cu/ATP/Hx(PA) as well as Cu/(ATP)(PA) species are formed. The type of the formed Cu(II) complexes depends on pH of the solution. For a low pH value the complexation appears between Cu(II) and ATP molecules via oxygen atoms of phosphate groups. For a very high pH value, where ATP is hydrolyzed, the Cu(II) ions are bound to the nitrogen atoms of polyamine molecules. We did not detect any direct coordination of the N7 nitrogen atom of adenosine to Cu(II) ions. It means that the CuN7 interaction is an indirect type and can be due to noncovalent interplay including water molecule. EPR studies were performed at glassy state (77K) after a fast freezing both for binary and ternary systems. The glassy state EPR spectra do not reflect species identified in titration studies indicating significant effect of rapid temperature decrease on equilibrium of Cu(II) complexes. We propose the molecular structure of all the studied complexes at the glassy state deduced from EPR and optical spectroscopy results.

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, ...

Complexation reactions of Cu(II) in the system with l -lysine as well as biogenic amines – PA (putrescine – Put, spermidine – Spd and spermine – Spm) were investigated. It was found that at low pH in Cu(II)/Lys/Put and Cu(II)/Lys/Spm systems molecular complexes of M(Lys)⋯PA type are formed with putrescine and spermine in the outer coordination sphere. In contrast to the above systems, molecular adducts do not occur in the spermidine systems. At higher pH, heteroligand species are formed with polyamines in the inner coordination sphere. In solution, the molecular composition, stability and mode of coordination in Cu(Lys)Hx(PA) species were established using potentiometric and spectral techniques. In the glassy state at 77 K, only stationary Cu(II)-complexes exist. According to the EPR spectra, lysine is a strongly coordinating molecule compared to the polyamines. The influence of metal ions on the formation of binary Lys/Pa molecular complexes was calculated. It was found for the binary Lys/Spm system, that the introduction of decreasing amounts of Cu(II) to the binary ligand1/ligand2 systems to the level of 0.01 mM resulted in changes in the concentration of the molecular complexes in aqueous solution. At the level of Cu(II) above 5 mM all molecular complexes disappear.

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), x = 2–4, 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 nucleoti...

Histamine–copper(II) complexes have been studied using experimental methods and density functional theory. Preferred coordination centres and possible structures of aqua complexes have been determined. On the basis of equilibrium and spectroscopic studies the endocyclic nitrogen atom has been confirmed to as a coordinating centre in the CuH(Hist), Cu(Hist) and Cu(Hist)(OH) complexes. The involvement of the amino group linked to the aliphatic chain in the Cu(II) coordination has been additionally proven by the detection of the Cu(Hist) and Cu(Hist)(OH) complexes. The computed stabilisation energies demonstrate that the Cu(H 2 O) 4 (Hist) and Cu(OH)(Hist)(H 2 O) 3 chelates as well as the CuH(H 2 O) 5 (Hist) compounds are the most energetically stable in the media studied. The most stable conformers of the neutral form of the histamine molecule are in the Cu(Hist) and Cu(Hist)(OH) species. These complexes have a gauche structure stabilized by an intramolecular hydrogen bond. The electronic Jahn–Teller effect is mainly responsible for the tetragonal distortion of the octahedral MHL–(H 2 O) 5 complex. Strong electrostatic interactions and polarisation effects contribute to the enhanced stability for all of the complexes studied. The results of the computations confirm that histamine is effective in coordinating to the Cu(II) ions in biological systems. The theoretical results fully confirm the coordination modes proposed in the experiment and predict the most reliable geometry and energetic stability of the aqua complexes.

Interactions of aspartic acid between 1,3-diaminopropane ( tn ) and 1,4-diaminobutane ( Put ) 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. The interaction centres and coordination sites were identified by spectroscopic methods. Each of the ligands has both negative and positive interaction centres. In aspartic acid such centres are carboxyl groups and amine group, while in the polyamine molecules – protonated amine groups. The centres are also the potential sites of the coordination of metal ions. Analysis of the log K e values of the adducts in the systems with polyamines has shown that the stability of the adducts in the metal-free systems depends on a significant degree on the steric factor that is the length of the polyamine. In some species the inversion effect, hitherto not reported in literature, was found. In the ternary systems including Cu(II) ions, only protonated species are formed, including molecular complexes with intermolecular interactions and metallation through the oxygen atoms of carboxyl groups and amine groups of the amino acid. In the adducts the protonated diamine is in the outer coordination sphere and is involved in noncovalent interactions with the anchoring CuH(Asp) or Cu(Asp) complexes.

Complexation reactions in the quaternary system Cu/ATP/3,3,3-tet/Urd have been studied. The stability constants of the complexes of the Cu(ATP)(3,3,3-tet)H(x)(Urd) type have been determined by computer analysis of the potentiometric titration. On the basis of the results of spectroscopic as well as equilibrium studies, the mode of interactions has been proposed. Metal ions coordinate phosphate groups of ATP and nitrogen atoms of polyamine. It has been established that in the conditions of the complex Cu(ATP)(3,3,3-tet) formation, uridine introduced into the Cu(II)/ATP/3,3,3-tet ternary system is involved in hydrogen bonding with the endocyclic nitrogen atoms N(1) and N(7) of the ATP purine ring and formation of the adduct Cu(ATP)(3,3,3-tet)H(Urd) is observed. Introduction of metal ions into the system changes substantially the mode of interactions between complementary base pairs relative to that proposed in the Watson and Crick model.

The interactions of Cu(II) ions with adenosine-5'-monophosphate (AMP), cytidine-5'-monophosphate (CMP) and 1,12-diamino-4,9-dioxadodecane (OSpm) were studied. A potentiometric method was applied to determine the composition and stability constants of complexes formed, while the mode of interactions was analysed by spectral methods (ultraviolet and visible spectroscopy (UV-Vis), electron paramagnetic resonance (EPR), (13)C NMR, (31)P NMR). In metal-free systems, molecular complexes nucleotide-polyamine (NMP)H(x)(OSpm) were formed. The endocyclic nitrogen atoms of the purine ring N(1), N(7), the nitrogen atom of the pyrimidine ring N(3), the oxygen atoms of the phosphate group of the nucleotide and the protonated nitrogen atoms of the polyamine were the reaction centres. The mode of interaction of the metal ion with OSpm and the nucleotides (AMP or CMP) in the coordination compounds was established. In the system Cu(II)/OSpm the dinuclear complex Cu(2)(OSpm) forms, while in the ternary systems Cu(II)/nucleotide/OSpm the species type MH(x)LL' and MLL' appear. In the MH(x)LL' type species, the main centres of copper (II) ion binding in the nucleotide are the phosphate groups. The protonated amino groups of OSpm are involved in non-covalent interaction with the nitrogen atoms N(1), N(7) or N(3) of the purine or pyrimidine ring, whereas at higher pH, deprotonated nitrogen atoms of polyamine are engaged in metallation in MLL' species.

Interactions between the nucleotides: adenosine-5′-diphosphate (ADP) and adenosine-5′-triphosphate (ATP) with NiII and CoII ions, as well as with spermine (Spm) and 1,11-diamine-4,8-diazaundecane (3,3,3-tet) are the subject of this study. Composition and stability constants of mixed complexes thus formed have been determined on the basis of the potentiometric measurements, whereas interaction centres in ligands have been identified by VIS and NMR spectral parameter analysis. Mixed tetraprotonated complexes with NiII, i.e. Ni(ADP)H4(Spm), Ni(ATP)H4(Spm), Ni(ADP)H4(3,3,3-tet) and Ni(ATP)H4(333-tet), are identified as ML·······L′ type adducts, in which the main coordination centre is the nucleotide nitrogen N(1) or N(7) donor atom, and the fully protonated polyamine is engaged in noncovalent interactions with nucleotide phosphate group oxygen atoms. Ni(ADP)H2(Spm), Ni(ATP)H2(Spm), Ni(ADP)H2(3,3,3-tet) and Ni(ATP)H2(3,3,3-tet) complexes represent the {N3} coordination type In diprotonated mixed complexes of NiII with spermine are weak noncovalent interligand interactions, providing an additional stabilising effect. Formation of ML·······L′ type molecular complexes has been observed in systems with CoII: Co(ADP)H4(Spm), Co(ATP)H4(Spm), Co(ADP)H4(3,3,3-tet) and Co(ATP)H4(3,3,3-tet), in which the N(7) atom and oxygen atoms of the phosphate group are involved in coordination and the fully protonated polyamine is engaged in noncovalent interactions with the nucleotide N(1).

Metal ions and polyvalent organic cations take part in many processes proceeding in living organisms. These processes are associated with the formation of coordination compounds and molecular complexes. An important group of bioligands is made up of biogenic amines, which occur in practically all forms of organisms and their reactions with nucleic acids play an essential role in processes of genetic information transfer. Metals present in cells should be considered as interfering agents, which change the character of interactions. Reactions, including the formation of molecular complexes and metallation of a number of polyamines, have been described. The effectiveness of non-covalent interactions of amines, besides charge, is determined by structural factors (this fact elucidates reaction specificity) and these interactions are of an ion–ion, ion–dipole type, both in binary and ternary systems, that include fragments of nucleic acids (nucleosides, nucleotides) and metal ions, as well. Differences in the character of the interactions can elucidate different biological activity of biogenic amines compared to their analogues, not occurring in living organisms. Principal metallation sites of discussed bioligands in ternary sysytems, including fragments of nucleic acids, are amino groups of polyamines and endocyclic nitrogen atoms N(1), N(7) and N(3) of purine and pyrimidine rings of nucleosides as well as phosphate groups of nucleotides, respectively.

The interactions of adenosine 5'-diphosphate (ADP) with some polyamines (PA) (1,3-diaminopropane (tn), 1,4-diaminobutane (Put), 1,7-diamino-4-azaheptane (3,3-tri) and 1,8-diamino-4-azaoctane (Spd)) both in presence and in the absence of metal ions (Cu(II), Cd(II) and Hg(II)) have been studied. In the metal-free systems the formation of adducts (ADP)Hx(PA) has been observed, in which the main reaction centres are the endocyclic nitrogen atoms of the purine ring, the phosphate group of the nucleotide and the protonated nitrogen atoms of the polyamine. The effectiveness of the phosphate group in formation of adducts has been found to decrease in the series Put > Spd > Spm and to be lower than in the reactions with shorter homologues of biogenic amines. In the ternary systems with metal ions the formation of molecular complexes (ML L' type) has been evidenced in which the protonated polyamine interacts with the nitrogen atoms N(1) or N(7) of the purine ring of the nucleotide. In the ternary systems Cu(II)/ADP/polyamine the coordination dichotomy observed in the binary system Cu(II)/ADP disappears. In the systems with Hg(II) ions the pH range of the dichotomy is extended, while for the systems Cd(II)/ADP/polyamine no changes of the range relative to the binary system Cd(II)/ADP have been noted.

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 .

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.

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. © 2001 Published by Elsevier Science Ltd.

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.

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.

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.

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.

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.

The occurrence of non-covalent interactions and formation of molecular complexes between adenosine 5′-monophosphate (AMP) or cytidine 5′-monophosphate (CMP) and the polyamines, putrescine, 1,7-diamino-4-azaheptane (3,3-tri), spermidine and 1,11-diamino-4,8-diazaundecane (3,3,3-tet), were detected in metal-free systems. The stoichiometric composition of the adducts and their stability constants were determined on the basis of computer analysis of the titration data, taking into account the fact that the acid–base properties of the system change as a result of these interactions. Spectral analysis allowed an identification of the interaction centers in the adducts as protonated amine groups of polyamines, phosphate groups as well as nitrogen atoms of high electron density from nucleotides. Unexpectedly, no participation of the phosphate group from AMP in the formation of molecular complexes with tetramine-3,3,3-tet was detected. The stoichiometric composition and stability constants of mixed-ligand complexes in the systems of Cu(II) with AMP or CMP and polyamines were obtained. Analysis of the results of equilibrium studies and 13 C, 31 P NMR, UV–Vis, IR and EPR data permitted determination of the mode of coordination. In the systems with metal ions, the formation of molecular complexes Cu(CMP)H 4 (3,3-tri) was found, apart from heteroligand complexes of the MLL′ and MLL′H x type. In protonated complexes the occurrence of non-covalent interactions leading to stabilization of the coordination compounds was observed. The differences in the character of coordination biogenic amines and their biologically inactive analogs were identified.