Non-covalent and coordination interactions in Cu(II) systems with uridine, uridine 5'-monophosphate and triamine or tetramine as biogenic amine analogues in aqueous solutions

Reactions of metallation and non-covalent interactions have been studied in ternary systems of Cu(II) ions with uridine, uridine 5'-monophosphate and diamines or triamines. It has been found that in metal-free systems the reaction centres of the nucleoside with the polyamine are the donor nitrogen atoms N(3) and protonated -NH(x) groups of the amines. In comparison to systems with adenosine or cytidine, the pH range of complex formation is shifted towards higher values. It is a consequence of significantly higher basicity of uridine and in agreement with the ion-ion, ion-dipole interaction model assumed. Formation of molecular complexes of uridine 5'-monophosphate with polyamines at a low pH is the result of activity of the phosphate group which plays the role of a negatively charged reaction site. Non-covalent interactions interfere in processes of bioligand metallation. Centres of weak interactions are simultaneously binding sites of metal ions. In protonated Cu(Urd)(PA)H(x) complexes, coordination has been found to involve the N(3) atom from the nucleoside and two donor nitrogen atoms from the polyamine (PA). In the heteroligand species Cu(Urd)(PA), despite deprotonation of all amine groups, one of these groups is located outside the inner coordination sphere. In complexes with uridine-5'-monophosphate, the phosphate group is active in metallation. Moreover, in certain coordination compounds this group is engaged in non-covalent interactions with PA molecules, despite binding Cu ions, as has been shown on the basis of equilibrium and spectral studies.     

Coordination mode of adenosine 5'-diphosphate in ternary systems containing Cu(II), Cd(II) or Hg(II) ions and polyamines

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.     

Mixed-ligand complexes of copper(II) ions with AMP and CMP in the systems with polyamines and non-covalent interaction between bioligands

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 13C, 31PNMR, 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)H4(3,3-tri) was found, apart from heteroligand complexes of the MLL' and MLL'Hx 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.     

Interactions of 1,12-diamino-4,9-dioxadodecane (OSpm) and Cu(II) ions with pyrimidine and purine nucleotides: adenosine-5'-monophosphate (AMP) and cytidine-5'-monophosphate (CMP)

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.     

Copper(II) complexes with uridine,uridine 5'-monophosphate,spermidine, or spermine in aqueous solution

Molecular complexes of the types (Urd)H(x)(PA) and (UMP)H(x)(PA) are formed in the uridine (Urd) or uridine 5'-monophosphate (UMP) plus spermidine or spermine systems, as shown by the results of equilibrium and spectral studies. Overall stability constants of the adducts and equilibrium constants of their formation have been determined. An increase in the efficiency of the reaction between the bioligands is observed with increasing length of the polyamine. The pH range of adduct formation is found to coincide with that in which the polyamine is protonated while uridine or its monophosphate is deprotonated. The -NH(x)(+) groups from PA and the N(3) atom of the purine base as well as phosphate groups from the nucleotides have been identified as the significant centres of non-covalent interactions. Compared to cytidine, the pH range of Urd adduct formation is shifted significantly higher due to differences in the protonation constants of the endocyclic N(3) donor atoms of particular nucleosides. Overall stability constants of the Cu(II) complexes with uridine and uridine 5'-monophosphate in ternary systems with spermidine or spermine have been determined. It has been found from spectral data that in the Cu(II) ternary complexes with nucleosides and polyamines the reaction of metallation involves mainly N(3) atoms from the pyrimidine bases, as well as the amine groups of PA. This unexpected type of interaction has been evidenced in the coordination mode of the complexes forming in the Cu-UMP systems including spermidine or spermine. Results of spectral and equilibrium studies indicate that the phosphate groups taking part in metallation are at the same time involved in non-covalent interaction with the protonated polyamine.     

Interaction centres of purine nucleotides: adenosine-5'-diphosphate and adenosine-5'-triphosphate in their reactions with tetramines and Cu(II) ions

The interactions between the nucleotides: adenosine-5'-diphosphate (ADP) and adenosine-5'-triphosphate (ATP) with spermine (Spm) and 1,11-diamine-4,8-diazaundecane (3,3,3-tet), as well as Cu(II) ions are studied. In the metal-free systems nucleotide-polyamine molecular complexes have been found to form, in which the interaction centres are the nitrogen atoms of the purine ring N(1) and N(7), oxygen atoms of the phosphate group of the nucleotide (for 3,3,3-tet) and protonated nitrogen atoms of the polyamine. Significant differences in the mode of metallation between the systems with Spm and 3,3,3-tet have been established. In the systems with Spm, the main products are protonated species with [N(7),O] chromophore and the nitrogen N(1) is involved in the intramolecular interaction additionally stabilising the complex. In the systems with 3,3,3-tet the formation of metal-ligand-ligand (MLL) species has been observed, in which the oxygen atoms from the phosphate group and the nitrogen atoms from the polyamine are involved in the metallation, while the N(1) and N(7) atoms from the purine ring of the nucleotide remain outside the inner coordination sphere of the copper ion. The main centre of metallation in the nucleotide, both with Spm and 3,3,3-tet, is the phosphate group of the nucleotide.     

The effect of spermine concentration on the solution structure of complexes formed in copper(II)/adenosine 5′-triphosphate/phosphoserine system

Quaternary systems of copper(II) complexes with adenosine 5′-triphosphate, O-phospho l-serine and with equimolar or excessive amount of spermine have been investigated. The studies have been performed in aqueous solution. Types of complexes and the overall stability constants have been determined using the potentiometric method with computer analysis of the data. On the basis of the results of spectroscopic studies (nuclear magnetic resonance, visible, circular dichroism, Raman, infrared and electron paramagnetic resonance spectroscopies) as well as equilibrium studies, the mode of interactions has been proposed. The reaction centers in the systems studied are the phosphate, carboxyl and amine groups from phosphorylated serine, heterocyclic nitrogen atom from purine ring and phosphate groups from adenosine 5′-triphosphate as well as amine groups from polyamine. The influence of change in the concentration of the polyamine (spermine) on the mode of coordination is discussed. It has been shown that in the physiological conditions an increase in the polyamine concentration changes the mode of metal bonding in the CuH₃(ATP)(Ser-P)(Spm) complexes (isomer I — coordination {2 N,O_x}, isomer II — coordination {3 N,O_x} and significant differences in sites of interaction).     

Interaction centres of pyrimidine nucleotides: cytidine-5'-diphosphate (CDP) and cytidine-5'-triphosphate (CTP) in their reactions with tetramines and Cu(II) ions

The interactions between pyrimidine nucleotides: cytidine-5'-diphosphate (CDP) and cytidine-5'-triphosphate (CTP) and Cu(II) ions, spermine (Spm) and 1,11-diamino-4,8-diazaundecane (3,3,3-tet) have been studied. The composition and stability constants of the complexes formed have been determined by means of the potentiometric method, while the centres of interactions in the ligands have been identified by the spectral methods (UV-Vis, Ultraviolet and Visible spectroscopy; EPR, electron spin resonance; NMR). In the systems without metal, formation of the molecular complexes nucleotide-polyamine with the interaction centres at the endocyclic nitrogen atom of purine ring N3, the oxygen atoms of the phosphate group from the nucleotide and protonated nitrogen atoms of the polyamine have been detected. Significant differences have been found in the metallation between the systems with Spm and with 3,3,3-tet. In the systems with spermine, mainly protonated species are formed with the phosphate group of the nucleotide and deprotonated nitrogen atoms of the polyamine making the coordination centres, while the donor nitrogen atom of the nucleotide N3 is involved in the intramolecular interligand interactions, additionally stabilising the complex. In the systems with 3,3,3-tet, the MLL' type species are formed in which the oxygen atoms of the phosphate group and nitrogen atoms of the polyamine are involved in metallation, whereas the N3 atom from the pyrimidine ring of the nucleotide is located outside the inner coordination sphere of copper ion. The main centre of Cu(II) interaction in the nucleotide, both in the system with Spm and 3,3,3-tet is the phosphate group of the nucleotide.     

Density functional theory study on the interaction between keto-9H guanine and aspartic acid

A theoretical study was performed using density functional theory (DFT) to investigate hydrogen bonding interactions in signature complexes formed between keto-9H guanine (Gua) and aspartic acid (Asp) at neutral pH. Optimized geometries, binding energies and the theoretical IR spectra of guanine, aspartic acid and their corresponding complexes (Gua-Asp) were calculated using the B3LYP method and the 6-31+G(d) basis set. Stationary points found to be at local minima on the potential energy surface were verified by second derivative harmonic vibrational frequency calculations at the same level of theory. AIM theory was used to analyze the hydrogen bonding characteristics of these DNA base complex systems. Our results show that the binding motif for the most stable complex is strikingly similar to a Watson-Crick motif observed in the guanine-cytosine base pair. We have found a range of hydrogen bonding interactions between guanine and aspartic acid in the six complexes. This was further verified by theoretical IR spectra of ω(C-H---O-H) cm⁻¹ stretches for the Gua-Asp complexes. The electron density plot indicates strong hydrogen bonding as shown by the 2p _z dominant HOMO orbital character.     

Electrostatic calculations for assignment of infrared difference bands to carboxyl groups getting protonated during protein reactions

Fourier transform infrared (FTIR) difference spectroscopy is predestined to monitor the protonation of carboxyl groups during protein reactions, making glutamic and aspartic amino acids unique to follow proton pathways. The absorption of the corresponding vibrations are clearly distinguishable from the absorption of other amino acids. However, the assignment to specific groups within the protein needs additional information, e.g., from induced spectral changes due to isotopic labeling or mutation. Here, the capability of electrostatic calculations to assign IR difference bands to specific carboxyl groups getting protonated is demonstrated by the ion pump mechanism of the sarcoplasmic reticulum Ca(2+)-ATPase. Active Ca(2+) transport is coupled to the hydrolysis of ATP. Two Ca(2+) ions are transported per ATP hydrolysed and two or three H(+) ions are countertransported. FTIR difference spectra show that during the Ca(2+) release step, carboxyl groups become protonated. Multiconformation continuum electrostatic calculations (MCCE) have been carried out to determine the equilibrium distribution of residue ionization and side chain conformation in dependence of pH. Available structural X-ray data from the calcium-bound and the calcium-free state allows us to simulate the transition between the two states monitored in the IR difference spectra. Exemplarily for Asp 800, ligand of both calcium ions, it is shown that MCCE calculations can identify this specific Asp to contribute to the IR bands and therefore to take part in the proton countertransport of the Ca(2+)-ATPase. In addition, an energy analysis can be performed to understand what interactions shift the pK(a).     

Synthesis and characterization of new ternary Cu(II)-polyamines-ATP complexes

Four new complexes of Cu(II) of stoichiometry [Cu(ATP)(polyamine)] containing as ligands the polyamines (PA) ethylenediamine, 1,3-diaminopropane, spermidine or spermine and adenosine 5′triphosphate were prepared from aqueous solution at pH 6. The synthesis, characterization, thermogravimetric, vibrational spectroscopy, electron paramagnetic resonance analyses are described and show that these complexes have similar molecular structures. The infrared spectra and the thermal analysis are briefly discussed based on the peculiarities of the complexes. The IR spectra of the ligands and their copper complexes were used to assign the various groups and compare the shifts due to complexation. The EPR parameters values for the complexes show that Cu(II) is complexed in a similar way in the four complexes. Similarity in the coordination mode of complexes in solid state has been determined and discussed. The data obtained suggest that the four complexes present one water molecule of hydration and are complexed through two oxygen atoms from ATP and through two nitrogen atoms of each polyamine.     

A Combined Quantum/Classical Molecular Dynamics Study of the Catalytic Mechanism of HIV Protease

Based on available three-dimensional structures of enzyme-inhibitor complexes, the mechanism of the reaction catalysed by HIV protease is studied using molecular dynamics simulations with molecular mechanics and combined quantum-mechanics/molecular-mechanics potential energy functions. The results support the general acid/general base catalysis mechanism, with Asp25′ protonated in the enzyme-substrate complex. In the enzyme-substrate complex, the lytic water molecule binds at a position different from the positions of the hydroxyl groups in various aspartic protease-inhibitor complexes. The carboxyl groups at the active site also adopt a different orientation. However, when the lytic water molecule approaches the scissile peptide, the reaction centre changes gradually to a conformation close to that derived from X-ray diffraction studies of various enzyme-inhibitor complexes. The proton transfer processes can take place only after the lytic water molecule has approached the scissile peptide bond to a certain degree. Qualitatively, the free-energy barrier associated with the nucleophilic attack step, which takes place at physiological pH, is comparable with the acid or base-catalysed reactions of model systems. The structure of the tetrahedral intermediate resulting from the nucleophilic attack step also indicates a straightforward pathway of the next reaction step, i.e. the breaking of the C-N bond.     

Phosphoserine and specific types of its coordination in copper(II) and adenosine nucleotides systems - Potentiometric and spectroscopic studies

Ternary systems of copper(II) complexes with phosphoserine and adenosine 5′-monophosphate or adenosine 5′-diphosphate or adenosine 5′-triphosphate have been investigated. The studies have been performed in aqueous solution using the potentiometric method with computer analysis of the data, ¹³C and ³¹P nuclear magnetic resonance, visible and electron paramagnetic resonance spectroscopies. The overall stability constants of the complexes have been determined. Analysis of the equilibrium constants of the reaction have allowed determination of the effectiveness of the phosphate groups and donor atoms of heterocyclic rings in the process of complex formation. The potential reaction centres are the nitrogen atoms N(1) and N(7) and the phosphate group of the nucleotides as well as phosphate, carboxyl and amine groups from phosphorylated serine. Coordination sites of investigated ligands have been identified on the basis of the equilibrium constants analysis and spectroscopic studies.     

Metal dependent coordination of biomolecular ligand: X-ray crystal structures of copper, cobalt and calcium complexes of (3-hydroxy-5-(hydroxymethyl)-2-methylisonicotinic acid) 5-phosphate, an oxidized pyridoxal 5-phosphate

X-ray crystal analyses of divalent copper, cobalt and calcium complexes of monoanionic (3-hydroxy-5-(hydroxymethyl)-2-methylisonicotinic acid) 5-phosphate (L₁C₈H₉NO₇P⁻) revealed the chemical compositions of Cu ---L·3H₂O(1), Co ---L·5H₂O(2) and Ca·L₂·7H₂O (3) and the coordination structures which depend on the coordination abilities and chemical properties of the respective metal ions. Although 1 and 2 crystals showed similar features, i.e., presence of the metal ion at the crystallographic center of symmetry and octahedral six-coordination, the patterns of coordination with the ligand molecules differed. While direct coordination to the L carboxyl oxygen was observed in 1 crystals, all ligation positions in 2 crystals were occupied by water molecules. On the other hand, 3 crystals formed a pentagonal bipyramidal structure (seven-coordination), where oxygens of L phosphates and water molecules coordinated to the calcium ion. Each of the complex structures showed characteristic molecular packing depending on the pattern of coordination to the respective metal ion. L is monoanionic in all complex crystals, where the phosphate and carboxyl groups are deprotonated and pyridine nitrogen is protonated, and is neutralized by each metal ion. Crystal data: 1, monoclinic, space group P2₁/c, A = 5.4129(6), B = 10.515(2), C = 22.770(2) Å, β = 91.853(9)°, Z = 4, R = 0.0404 for 1834 observed reflections; 2, triclinic, space group

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, c = 6.789(3) Å, α = 96.84(3), β = 109.10(3), γ = 100.50(2)°, Z = 2, R = 0.0684 for 1605 observed reflections; 3, triclinic, , a = 10.069(2), B = 14.501(3), c = 10.051(1) Å, α = 100.75(1), β = 97.28(2), γ = 76.18(2)°, Z = 2, R = 0.0540 for 3637 observed reflections.     

Re-evaluating the effects of organic ligands on copper toxicity to barley root elongation in culture solution

Abstract

In the presence of weak ligands, both free ion activity and organic complexes of Cu should b considered when predicting Cu toxicity in aquatic and soil-plant systems. However, there is littl information about the quantitative contribution of Cu that is organically complexed to Cu toxicity. In thi study, a bioassay using barley root elongation in culture solution was used to investigate the effects o organic ligands with different conditional stability constants on Cu toxicity and the quantitativ contribution of the organically complexed Cu to the Cu toxicity. The results indicated that a significan decrease (p<0.05) in Cu toxicity, assessed by barley root elongation, was observed in response to th addition of organic ligands. The decrease differed, to some extent, with different organic ligands o disodium ethylenediaminetetraacetic acid (EDTA), nitrilotriacetic acid (NTA), oxalate and malate at low and constant free Cu²⁺ activity. Addition of EDTA or NTA resulted in strong reduction of Cu toxicity while modest reduction of Cu toxicity was observed for the addition of malate as the relatively wea ligand. Furthermore, the results of the present study revealed that the CuNTA^? and CuEDTA^2? complexes were not toxic, while the Cu–malate complexes were mildly toxic to barley root elongation More importantly, it was found that the toxicity of Cu–malate complexes were nearly 0.5-fold less than that of free Cu²⁺ ions.     

Robust building blocks for inorganic crystal engineering

We have prepared two ligands, 4- and 5-carboxylic acid pyrimidine, and synthesized and crystallographically characterized seven coordination complexes thereof. The need for potentially structurally disruptive counterions is eliminated by deprotonation of the carboxylic acid moieties; the carboxylates present in each structure act as counterions and balance the charge on the divalent metal ions leading to charge-neutral complex ions. The four new M(II)-complexes with 4-carboxylic acid pyrimidine (M = Ni, Cu, Zn, and Co) are isostructural as are the three M(II) complexes with 3-carboxylic acid pyrimidine (M = Ni, Cu, and Zn), indicating robust and reliable coordination modes for both ligands.     

Binding abilities of dehydropeptides towards Cu(II) and Ni(II) ions. Impact of Z–E isomerization on metal ion binding

The study on the binding ability of dehydro-tri- and tetrapeptides has shown that the α,β-double bond has a critical effect on the peptide coordination to metal ions. It may affect the binding of the vicinal amide nitrogens by the electronic effect and stabilize the complex due to steric effects. The (Z) isomer is the most effective in stabilizing of the complexes formed. The presence of large side chain in the dehydroamino acid residue may also be critical for the coordination mode in the metallopeptide systems.     

Probing the Cu and Zn binding affinity of histidine-rich glycoprotein

The zinc(II) and copper(II) binding ability of two oligopeptide fragments, Ac-HHPHG-NH₂ and Ac-HHPHGHHPHG-NH₂, derived from the repeat-region of the His-Pro-rich domain of histidine-rich glycoprotein (HRG) and the structure of the formed complexes have been investigated by potentiometry, NMR-, UV-visible-, CD-, SRCD- and EPR spectroscopy. Exclusive coordination of the side-chain imidazoles of the peptides has been observed with both metal ions in the acidic and neutral pH range. While the three His units of the pentapeptide resulted in a modest stability of the ML complexes, the decapeptide with its increased number of His residues offered a high-affinity metal binding site for both metal ions with the participation of at least four nitrogen donors. Due to the high number of potential donor groups, the formation of binding isomers of the protonated and parent complexes is very likely. Both peptides show a synchrotron radiation (SR) CD-pattern resembling to that of the polyproline II structure, similarly to that of the His-Pro-rich domain of the HRG protein. The longer sequence was shown to bind a second metal ion in the slightly acidic pH-range. The determined stability data suggest a remarkable extra stabilization emerging in the decapeptide for the coordination of the second metal ions, as compared to the ML complexes of the pentapeptide. Whether the observed cooperativity has similarities to the cooperative metal binding feature of HRG or the two phenomena have different sources is a question yet to be clarified.     

Utilization of (18‐Crown‐6)‐2,3,11,12‐tetracarboxylic Acid as a Chiral NMR Solvating Agent for Diamines and β‐Amino Acids

The compound (18‐crown‐6)‐2,3,11,12‐tetracarboxylic acid was evaluated as a chiral nuclear magnetic resonance (NMR) solvating agent for a series of diamines and bicyclic β‐amino acids. The amine must be protonated for strong association with the crown ether. An advantage of (18‐crown‐6)‐2,3,11,12‐tetracarboxylic acid over many other crown ethers is that it undergoes a neutralization reaction with neutral amines to form the protonated species needed for binding. Twelve primary diamines in neutral and protonated forms were evaluated. Diamines with aryl and aliphatic groups were examined. Some are atropisomers with equivalent amine groups. Others have two nonequivalent amine groups. Association equilibria for these systems are complex, given the potential formation of 2:1, 1:1, and 1:2 crown‐amine complexes and given the various charged species in solution for mixtures of the crown ether with the neutral amine. The crown ether produced enantiomeric differentiation in the ¹H NMR spectrum of one or more resonances for every diamine substrate. Also, a series of five bicyclic β‐amino acids were examined and (18‐crown‐6)‐2,3,11,12‐tetracarboxylic acid caused enantiomeric differentiation in the ¹H NMR spectrum of three or more resonances of each compound. Chirality 27:708–715, 2015. © 2015 Wiley Periodicals, Inc.     

The interactions of square platinum(II) complexes with guanine and adenine: a quantum-chemical ab initio study of metalated tautomeric forms

The influence of binding of square planar platinum complexes on tautomeric equilibria of the DNA bases guanine and adenine was investigated using the density functional B3LYP method. Neutral trans-dichloro(amine)-, +1 charged chloro(diamine)-, and +2 charged triamine-platinum(II) species were chosen for coordination to bases. Only the N₇ interaction site of the bases was considered. The calculations demonstrate that the neutral platinum adduct does not change the tautomeric equilibria of the bases. Furthermore, N₇ binding of the neutral Pt adduct moderately reduces the probability of protonation of the N₁ position of adenine. Larger effects can be observed for +1 and mainly +2 adducts, but these can be rationalized by electrostatic effects. Since the electrostatic effects are expected to be efficiently compensated for by a charged backbone of DNA and counterions in a polar solvent, no dramatic increase in mispair formation is predicted for Pt(II) adducts, which is in agreement with experiment. The interaction energies between Pt adducts and the nucleobases were also evaluated. These interaction energies range from ca. 210 kJ/mol for neutral adducts, interacting with both bases and their tautomers, up to 500 kJ/mol for the +2 charged adducts, interacting with the keto-guanine tautomer and the anti-imino-adenine tautomer. The surprisingly large interaction energy for the latter structure is due to the strong H-bond between the NH₃ ligand group of the metal adduct and the N₆ nitrogen atom of the base. Received: 6 July 1999 / Accepted: 7 December 1999