Nucleobase Complexes Research Articles

A comparative DFT study of some N-based aromatic ligand metal complexes as anticancer agents and analysis of their mode of interaction with DNA base pair

Metal complexed anticancer agents interact with DNA nucleobase pairs (AT and GC) through different types of binding mode such as intercalation, groove binding, covalent binding, etc. Minor and major groove binding mechanism of DNA base pair is the key factor for all kinds of anticancer agent; as metal complexes have a great affinity to bind with DNA nucleobase either through minor or major groove. Ligands in metal complexes also play a vital role during the interaction with DNA base pairs; these ligands directly interact with DNA through different interacting modes. Generally, anticancer agents with less sterically hindered N-based aromatic and planar ligands are the key component for DNA binding; as the structure of such ligands are quite compatible for following intercalation and groove binding mechanism. Since, the experimental investigation for drug-DNA nucleobase complexes are extremely complicated, therefore; quantum mechanical calculations might be very helpful for computing the actual interactions in drug-DNA complexes. Quantum mechanical approaches such as density functional theory (DFT) might be a very important and useful tool to investigate the actual mode of interaction of metal complexed antitumor agents with DNA nucleobase. Herein, we have taken some metal complexes with N-based aromatic ligands as antitumor agents to investigate the proper mode of interaction between drug-DNA complexes.

Cover Picture: Hydrogen‐Bonded Metal–Nucleobase Frameworks for Efficient Separation of Xenon and Krypton (Angew. Chem. Int. Ed. 11/2022)

Hydrogen-bonded frameworks self-assembled from metal–nucleobase complexes and hexafluoro anions are reported by Wei Zhou, Zongbi Bao et al. in their Research Article (e202117609). Amino-rich ligands provide multiple H-bonding sites to stabilize the frameworks. In the confined channels, the electron-rich anions combined with the electron-deficient purine rings generate a micro-electric field to polarize and lock Xe atoms, thus achieving highly efficient Xe/Kr separation under ambient conditions.

Quantum Mechanical Study of some Intercalating and Groove Binding Anticancer Drugs with AT and GC Base Pair of DNA Nucleobase

Anticancer drugs bind with DNA nucleobase pairs (AT and GC) through different binding modes such as intercalation, groove binding, covalent binding etc. Quantum mechanical DFT method is quite useful for computing the interaction energy value for anticancer drug-DNA nucleobase complexes. In our study, we have taken some of the anticancer drugs to investigate the interaction energy for drug-DNA complexes. Among the different binding modes of anticancer drugs; minor and major groove binding in DNA base pair is also an important aspect for anticancer drugs; therefore some anticancer drugs may be minor groove specific and some may be major groove specific. Since, such sequence-specific experimental studies for drug-DNA nucleobase complexes are very complicated and hence this may be investigated by using quantum mechanical theoretical studies, using M062X basis set. Our studies reveal that the stacked models of anticancer drugs-DNA nucleobase (AT and GC) complexes always show negative interaction energy values and among all such complexes the most negative interaction energy value results the most stable and favoured stacked systems. The stacking interaction energies for anticancer drugs-DNA nucleobase (AT and GC) complexes can easily be reflected in the interaction of energy plots.

Understanding structural and molecular properties of complexes of nucleobases and Au13 golden nanocluster by DFT calculations and DFT-MD simulation

The characterization of the complexes of biomolecules and nanostructures is highly interesting and benefits the rational development and design of nano-materials and nano-devices in nano-biotechnology. In this work, we have used dispersion corrected density functional theory (DFT-D) as well as DFT based molecular dynamics simulations to provide an atomistic understanding of interaction properties of DNA nucleobases and Au13 nanocluster. Various active sites of interacting molecules considering their relative orientation and distance are explored. Our goal is to stimulate the binding characteristics between two entities and evaluate this through the interaction energy, the charge transfer, the electronic structure, and the specific role of the molecular properties of the nucleobase–Au13 system. The primary outcomes of this comprehensive research illuminated that nucleic bases have potent affinity for binding to the Au cluster being chemisorption type and following the trend: Adenine > Cytosine > Guanine > Thymine. The AIM analysis indicated that the binding nature of the interacting species was predominantly partial covalent and high polar. We discuss the bearing of our findings in view of gene-nanocarrier, biosensing applications as well as nanodevices for sequencing of DNA.

Investigating the mapping of chromophore excitations onto the electron detachment spectrum: photodissociation spectroscopy of iodide ion-thiouracil clusters.

Laser photodissociation spectroscopy (3.1-5.7 eV) has been applied to iodide complexes of the non-native nucleobases, 2-thiouracil (2-TU), 4-thiouracil (4-TU) and 2,4-thiouracil (2,4-TU), to probe the excited states and intracluster electron transfer as a function of sulphur atom substitution. Photodepletion is strong for all clusters (I-·2-TU, I-·4-TU and I-·2,4-TU) and is dominated by electron detachment processes. For I-·4-TU and I-·2,4-TU, photodecay is accompanied by formation of the respective molecular anions, 4-TU- and 2,4-TU-, behaviour that is not found for other nucleobases. Notably, the I-·2TU complex does not fragment with formation of its molecular anion. We attribute the novel formation of 4-TU- and 2,4-TU- to the fact that these valence anions are significantly more stable than 2-TU-. We observe further similar behaviour for I-·4-TU and I-·2,4-TU relating to the general profile of their photodepletion spectra, since both strongly resemble the intrinsic absorption spectra of the respective uncomplexed thiouracil molecule. This indicates that the nucleobase chromophore excitations are determining the clusters' spectral profile. In contrast, the I-·2-TU photodepletion spectrum is dominated by the electron detachment profile, with the near-threshold dipole-bound excited state being the only distinct spectral feature. We discuss these observations in the context of differences in the dipole moments of the thionucleobases, and their impact on the coupling of nucleobase-centred transitions onto the electron detachment spectrum.

Templated Polymerization of Nucleobase Complexes via Molecular Recognition.

Macromolecules have a strong tendency to interact with each other in solution to form a supramolecular structure through various secondary binding forces. In this study, nucleobase-containing templates poly(9-(4-vinylbenzyl)adenine) (PS AH) and poly(1-(4-vinylbenzyl)cytosine) (PS CH) are prepared by reversible addition-fragmentation chain transfer (RAFT) polymerization. Vinylbenzyl thymine (MS T) is polymerized in the presence of these two nucleobase-containing templates. MS T shows higher affinities toward the template PS AH compared with the template PS CH. In accordance with the Watson-Crick pairing principle, thymine forms hydrogen bonding (H-bonding) with adenine, but not between thymine and cytosine. A complex is formed when PS AH is used as template which indicates that there is a template polymerization of nucleobase complexes via molecular recognition.

Effect of Alkali Metal Cations on Length and Strength of Hydrogen Bonds in DNA Base Pairs.

For many years, non-covalently bonded complexes of nucleobases have attracted considerable interest. However, there is a lack of information about the nature of hydrogen bonding between nucleobases when the bonding is affected by metal coordination to one of the nucleobases, and how the individual hydrogen bonds and aromaticity of nucleobases respond to the presence of the metal cation. Here we report a DFT computational study of nucleobase pairs interacting with alkali metal cations. The metal cations contribute to the stabilization of the base pairs to varying degrees depending on their position. The energy decomposition analysis revealed that the nature of bonding between nucleobases does not change much upon metal coordination. The effect of the cations on individual hydrogen bonds were described by changes in VDD charges on frontier atoms, H-bond length, bond energy from NBO analysis, and the delocalization index from QTAIM calculations. The aromaticity changes were determined by a HOMA index.

Theoretical studies on the electronic and optoelectronic properties of [A.2AP(w)/A*.2AP(WC)/C.2AP(w)/C*.2AP(WC)/C.A(w)/C*.A(WC)]–Au8 mismatch nucleobase complexes

ABSTRACTThe electronic and optoelectronic properties of [A.2AP(w)/A*.2AP(WC)/C.2AP(w)/C*.2AP(WC)/C.A(w)/ C*.A(WC)]–Au8 metal-mismatch nucleobase complexes are investigated by means of density functional theory and time-dependent methods. We selected these mispairs as 2-aminopurine (2AP) produces incorporation errors when binding with cytosine (C) into the wobble (w) C·2AP(w) mispair, and is tautomerised into Watson–Crick (WC)-like base mispair C*·2AP(WC) and less effectively produces A.2AP(w)/A*.2AP(WC) mispairs. The vertical ionisation potential, vertical electron affinity, hardness and electrophilicity index of these complexes have also been discussed. The modifications of energy levels and charge density distributions of the frontier orbitals are also analysed. The absorption spectra of these complexes lie in the visible region, which suggests their application in fluorescent-bio imaging. The mechanism of cooperativity effect is studied by molecular orbital potential (MEP), atoms-in-molecules (AIM) and natural bond orbital analyses. Most metalated pairs have smaller HOMO–LUMO band gaps than the isolated mismatch nucleobases which suggest interesting consequences for electron transfer through DNA duplexes.

Defect-Based Modulation of Optoelectronic Properties for Biofunctionalized Hexagonal Boron Nitride Nanosheets.

Defect engineering potentially allows for dramatic tuning of the optoelectronic properties of two-dimensional materials. With the help of DFT calculations, a systematic study of DNA nucleobases adsorbed on hexagonal boron-nitride nanoflakes (h-BNNFs) with boron (VB ) and nitrogen (VN ) monovacancies is presented. The presence of VN and VB defects increases the binding strength of nucleobases by 9 and 34 kcal mol-1 , respectively (h-BNNF-VB >h-BNNF-VN >h-BNNF). A more negative electrostatic potential at the VB site makes the h-BNNF-VB surface more reactive than that of h-BNNF-VN , enabling H-bonding interactions with nucleobases. This binding energy difference affects the recovery time-a significant factor for developing DNA biosensors-of the surfaces in the order h-BNNF-VB >h-BNNF-VN >h-BNNF. The presence of VB and VN defect sites increases the electrical conductivity of the h-BNNF surface, VN defects being more favorable than VB sites. The blueshift of absorption peaks of the h-BNNF-VB -nucleobase complexes, in contrast to the redshift observed for h-BNNF-VN -nucleobase complexes, is attributed to their observed differences in binding energies, the HOMO-LUMO energy gap and other optoelectronic properties. Time-dependent DFT calculations reveal that the monovacant boron-nitride-sheet-nucleobase composites absorb visible light in the range 300-800 nm, thus making them suitable for light-emitting devices and sensing nucleobases in the visible region.

Biomarkers of cigarette smoking and DNA methylating agents: Raman, SERS and DFT study of 3-methyladenine and 7-methyladenine

3-Methyladenine and 7-methyladenine are biomarkers of DNA damage from exposure to methylating agents. For example, the concentration of 3-methyladenine increases significantly in the urine of cigarette smokers. Surface-enhanced Raman spectroscopy (SERS) has shown much potential for detection of biomolecules, including DNA. Much work has been dedicated to the canonical nucleobases, with comparatively fewer investigations of modified DNA and modified DNA nucleobases. Herein, Raman spectroscopy and SERS are used to examine the adsorption orientations of 3-methyladenine and 7-methyladenine on Ag nanoparticles. Density functional theory (DFT) calculations at the B3LYP level are used to support the conclusions via simulated spectra of the nucleobases and of Ag+/nucleobase complexes. The results herein show that 7-methyladenine adsorbs upright via its N3 and N9 atoms side, similarly to adenine. 3-Methyladenine adsorbs in a very tilted or flat orientation on the Ag nanoparticles. These findings will be useful for future SERS or other nanoparticle-based bioanalytical assays for detection of these methyladenines or other modified nucleobases.

Metal Complexes of Mixed Nucleobases. Part I: Synthesis and Characterization of Copper(II), Zinc(II), Cadmium(II) and Mercury(II) Complexes of Adenine and Uracil

The complexes of Cu(II), Zn(II), Cd(II) and Hg(II) with adenine (AdeH) and uracil (UraH) have been synthesized and characterized by a combination of metal contents estimation, IR, UV-vis spectral data, thermogravimetric analysis (QSTG, TG and DSC) and magnetic susceptibility measurement. All the complexes are micro-crystalline, slightly soluble in water and decompose at high temperature. Both adenine and uracil deprotonated under experimental condition and then ligated to the metal ions as bidentate ligands through N(3) and N(9) of adeninato (Ade), and through N(3) and C(2)=O of uracilato (Ura) anions. On the basis of the metal contents, the complexes are formulated as [M(C5H4N5O)(C5H4N5)(H2O)2] [M = Cu(II), Zn(II) and Hg(II)] and [Cd(C5H4N5)(C4H3N2O2)(H2O)2].2H2O. The redox properties of copper and cadmium complexes were examined in aqueous solution by cyclic voltammetry. The voltammograms show quasi-reversible behavior for both the complexes. The X-ray powder diffraction study of the copper complex indicates that it is poorly crystalline in nature.
 Dhaka Univ. J. Sci. 64(2): 127-133, 2016 (July)

Binding energies of nucleobase complexes: Relevance to homology recognition of DNA.

The binding energies of complexes of DNA nucleobase pairs are evaluated using quantum mechanical calculations at the level of dispersion corrected density functional theory. We begin with Watson-Crick base pairs of singlets, duplets, and triplets and calculate their binding energies. At a second step, mismatches are incorporated into the Watson-Crick complexes in order to evaluate the variation in the binding energy with respect to the canonical Watson-Crick pairs. A linear variation of this binding energy with the degree of mismatching is observed. The binding energies for the duplets and triplets containing mismatches are further compared to the energies of the respective singlets in order to assess the degree of collectivity in these complexes. This study also suggests that mismatches do not considerably affect the energetics of canonical base pairs. Our work is highly relevant to the recognition process in DNA promoted through the RecA protein and suggests a clear distinction between recognition in singlets, and recognition in duplets or triplets. Our work assesses the importance of collectivity in the homology recognition of DNA.

NIMS: a database on nucleobase compounds and their interactions in macromolecular structures

The intense exploration of nucleotide-binding protein structures has created a whirlwind in the field of structural biology and bioinformatics. This has led to the conception and birth of NIMS. This database is a collection of detailed data on the nucleobases, nucleosides and nucleotides, along with their analogues as well as the protein structures to which they bind. Interaction details such as the interacting residues and all associated values have been made available. As a pioneering step, the diffraction precision index for protein structures, the atomic uncertainty for each atom, and the computed errors on the interatomic distances and angles are available in the database. Apart from the above, provision has been made to visualize the three-dimensional structures of both ligands and protein–ligand structures and their interactions inJmolas well asJSmol. One of the salient features of NIMS is that it has been interfaced with a user-friendly and query-based efficient search engine. It was conceived and developed with the aim of serving a significant section of researchers working in the area of protein and nucleobase complexes. NIMS is freely available online at http://iris.physics.iisc.ernet.in/nims and it is hoped that it will prove to be an invaluable asset.

Photoelectron spectroscopy of hexachloroplatinate-nucleobase complexes: Nucleobase excited state decay observed via delayed electron emission.

We report low-temperature photoelectron spectra of isolated gas-phase complexes of the hexachloroplatinate dianion bound to the nucleobases uracil, thymine, cytosine, and adenine. The spectra display well-resolved, distinct peaks that are consistent with complexes where the hexachloroplatinate dianion is largely intact. Adiabatic electron detachment energies for the hexachloroplatinate-nucleobase complexes are measured as 2.26-2.36 eV. The magnitudes of the repulsive Coulomb barriers (RCBs) of the complexes are all ∼1.7 eV, values that are lower than the RCB of the uncomplexed PtCl6 (2-) dianion as a result of charge solvation by the nucleobases. In addition to the resolved spectral features, broad featureless bands indicative of delayed electron detachment are observed in the 193 nm photoelectron spectra of the four clusters. The 266 nm spectra of the PtCl6 (2-) ⋅ thymine and PtCl6 (2-) ⋅ adenine complexes also display very prominent delayed electron emission bands. These results mirror recent results on the related Pt(CN)4 (2-) ⋅ nucleobase complexes [A. Sen et al., J. Phys. Chem. B 119, 11626 (2015)]. The observation of delayed electron emission bands in the PtCl6 (2-) ⋅ nucleobase spectra obtained in this work, as for the previously studied Pt(CN)4 (2-) ⋅ nucleobase complexes, is attributed to one-photon excitation of nucleobase-centred excited states that can effectively couple to the electron detachment continuum, producing strong electron detachment. Moreover, the selective, strong excitation of the delayed emission bands in the 266 nm spectra is linked to fundamental differences in the individual nucleobase photophysics at this excitation energy. This strongly supports our previous suggestion that the dianion within these clusters can be viewed as a "dynamic tag" which has the propensity to emit electrons when the attached nucleobase decays over a time scale long enough to allow autodetachment.

Analogues of Cis- and Transplatin with a Rich Solution Chemistry: cis-[PtCl2 (NH3 )(1-MeC-N3)] and trans-[PtI2 (NH3 )(1-MeC-N3)

Mono(nucleobase) complexes of the general composition cis-[PtCl2 (NH3 )L] with L=1-methylcytosine, 1-MeC (1 a) and L=1-ethyl-5-methylcytosine, as well as trans-[PtX2 (NH3 )(1-MeC)] with X=I (5 a) and X=Br (5 b) have been isolated and were characterized by X-ray crystallography. The Pt coordination occurs through the N3 atom of the cytosine in all cases. The diaqua complexes of compounds 1 a and 5 a, cis-[Pt(H2 O)2 (NH3 )(1-MeC)](2+) and trans-[Pt(H2 O)2 (NH3 )(1-MeC)](2+) , display a rich chemistry in aqueous solution, which is dominated by extensive condensation reactions leading to μ-OH- and μ-(1-MeC(-) -N3,N4)-bridged species and ready oxidation of Pt to mixed-valence state complexes as well as diplatinum(III) compounds, one of which was characterized by X-ray crystallography: h,t-[{Pt(NH3 )2 (OH)(1-MeC(-) -N3,N4)}2 ](NO3 )2 ⋅2 [NH4 ](NO3 )⋅2 H2 O. A combination of (1) H NMR spectroscopy and ESI mass spectrometry was applied to identify some of the various species present in solution and the gas phase, respectively. As it turned out, mass spectrometry did not permit an unambiguous assignment of the structures of +1 cations due to the possibilities of realizing multiple bridging patterns in isomeric species, the occurrence of different tautomers, and uncertainties regarding the Pt oxidation states. Additionally, compound 1 a was found to have selective and moderate antiproliferative activity for a human cervix cancer line (SISO) compared to six other human cancer cell lines.

Formation of polynuclear copper complexes of guanine-based nucleobases in the gas phase studied by ESI-MS

Electrospray ionization of water/methanol solutions containing the DNA nucleoside deoxyguanosine and Cu(II) sulphate provide direct experimental evidence for the formation of a series of charged clusters containing up to four Cu(II) ions and up to three sulphate anion plus a variable number of deoxyguanosine ligands, which we refer to as polynuclear copper complexes. The complexes are of the type [Cum(dGuo)n(SO4)m−1]2+ with m=2–4 and n=4–11. Complexes containing two and three Cu(II) ions have relative abundances in the range 1–13%, thus representing a significant fraction of all the Cu-containing ion species. Their chemical composition is determined by high resolution mass measurements and confirmed by comparison of experimental and simulated isotope patterns. Complex stabilities and some structural information are assessed by collision induced fragmentation experiments. In some specific cases ion mobility measurements have been exploited to resolve the contribution of singly and doubly charge ions overlapping in the same m/z region. Some feasible structures are proposed in which two Cu moieties are bridged by a sulphate anion. In addition, singly charged ions formally corresponding to a complex between a protonated ligand and a CuSO4 moiety ([Cu(dGuo+H)(dGuo)n−1SO4]+, n=2–5) are observed. Finally, the effect of the counter-anion in the stabilization of the polynuclear Cu complexes is studied in a series of experiments preformed using Cu(II) nitrate and chloride salts to replace CuSO4, and the latter is found to have the highest propensity for polynuclear copper cluster generation.

A computational proposal for the experimentally observed discriminatory behavior of hypoxanthine, a weak universal nucleobase

A computational model composed of six nucleobases was used to investigate why hypoxanthine does not yield duplexes of equal stability when paired opposite each of the natural DNA nucleobases. The magnitudes of all nearest-neighbor interactions in a DNA helix were calculated, including hydrogen-bonding, intra- and interstrand stacking interactions, as well as 1-3 intrastrand stacking interactions. Although the stacking interactions in DNA relevant arrangements are significant and account for at least one third of the total stabilization energy in our nucleobase complexes, the trends in the magnitude of the stacking interactions cannot explain the relative experimental melting temperatures previously reported in the literature. Furthermore, although the total hydrogen-bonding interactions explain why hypoxanthine preferentially pairs with cytosine, the experimental trend for the remaining nucleobases (A, T, G) is not explained. In fact, the calculated pairing preference of hypoxanthine matches that determined experimentally only when the sum of all types of nearest-neighbor interactions is considered. This finding highlights a strong correlation between the relative magnitude of the total nucleobase-nucleobase interactions and measured melting temperatures for DNA strands containing hypoxanthine despite the potential role of other factors (including hydration, temperature, sugar-phosphate backbone). By considering a large range of sequence combinations, we reveal that the binding preference of hypoxanthine is strongly dependent on the nucleobase sequence, which may explain the varied ability of hypoxanthine to universally bind to the natural bases. As a result, we propose that future work should closely examine the interplay between the dominant nucleobase-nucleobase interactions and the overall strand stability to fully understand how sequence context affects the universal binding properties of modified bases and to aid the design of new molecules with ambiguous pairing properties.

Quantum Mechanical Study of Physisorption of Nucleobases on Carbon Materials: Graphene versus Carbon Nanotubes

Quantum chemical calculations reveal that the binding energy of the carbon nanotube (CNT) and DNA/RNA nucleobase complexes is controlled by the curvature of the carbon nanotube. Graphene not only has higher affinity but also appears to be best suited to differentiate various nucleobases compared with carbon nanotubes. The dispersion-corrected DFT and M06-2X functionals are in excellent agreement with the experimental observations. Interestingly, nucleus-independent chemical shift (NICS) calculations indicate substantial enhancement of aromaticity for all nucleobases upon binding to graphene and CNT.

ChemInform Abstract: Synthesis and Characterization of Nickel(II) Complexes of Purine and Pyrimidine Bases. Crystal and Molecular Structure of trans-Bis( cytosine-O2)bis(ethylenediamine)nickel(II) Bis(tetraphenylborate). An Unusual Metal Binding Mode of C

Three nucleobase complexes [Ni(en) 2 (Ade)]Cl 2 , [Ni(en) 2 (Hyp)] Cl.0.5CH 3 OH.H 2 O and [Ni(en) 2 (Cyt) 2 ] [B(C 6 H 5 ) 4 ] 2 (en=ethylenediamine; Ade=adenine; Hyp=hypoxanthine; Cyt=cytosine) have prepared by reaction of Ni(en) 2 Cl 2 and the corresponding purine or pyrimidine base in a methanol or an ethanol-water medium. The cytosine complex was obtained in the form of suitable crystals for X-ray crystallography. The complex crystallizes in the monoclinic space group P2 1 /a

Irreversible Insertion of Benzonitrile into Platinum(II)−Nitrogen Bonds of Nucleobase Complexes. Synthesis and Structural Characterization of Stable Azametallacycle Compounds

Deprotonation of 1-methylcytosine (1-MeCy) and 9-methyladenine (9-MeAd) promoted by cis-[L(2)Pt(mu-OH)](2)(NO(3))(2) (L = PPh(3), PMePh(2), (1)/(2)dppe) in PhCN causes the irreversible insertion of a nitrile molecule into the Pt-N4 and Pt-N6 bonds of the cytosinate and adeninate ligands, respectively, to form the stable azametallacycle complexes cis-[L(2)PtNH=C(Ph){1-MeCy(-2H)}]NO(3) (L = PPh(3), 1; PMePh(2), 2; (1)/(2)dppe, 3) and cis-[L(2)PtNH=C(Ph){9-MeAd(-2H)}]NO(3) (L = PPh(3), 4; PMePh(2), 5) containing the deprotonated form of the molecules (Z)-9-N-(1-methyl-2-oxo-2,3-dihydropyrimidin-4(1H)-ylidene)benzimidamide and (Z)-N-(9-methyl-1H-purin-6(9H)-ylidene)benzimidamide. Single-crystal X-ray analyses of 2 and 4 show the metal coordinated to the N3 cytosine site [Pt-N3 = 2.112(7) A] and to the N1 site of adenine [Pt-N1 = 2.116(6) A] and to the nitrogen atom of the inserted benzonitrile [Pt-N2 = 2.043(6) and 2.010(6) A in 2 and 4, respectively], with the exocyclic nucleobase amino nitrogen bound to the carbon atom of the CN group. Complex 2, in solution, undergoes a dynamic process related to a partially restricted rotation around Pt-P bonds, arising from a steric interaction of the oxygen atom of the cytosine with one ring of the phosphine ligands. The reaction of 4 with acetylacetone (Hacac) causes the quantitative protonation of the anionic ligand, affording the acetylacetonate complex cis-[(PPh(3))(2)Pt(acac)]NO(3) and the free benzimidamide NH=C(Ph){9-MeAd(-H)}. In the same experimental conditions, complex 3 reacts with Hacac only partially.