Studies of the reaction products of adenosine with [Pt(NH3)3Cl]Cl and cis-Pt(NH3)2Cl2 by high performance liquid chromatography

The reaction products of adenosine with [Pt(NH₃)₃Cl]Cl or cis-Pt(NH₃)₂Cl₂ have been studied using high performance liquid chromatography and uv spectroscopy. The reaction of [Pt(NH₃)₃Cl]Cl with adenosine (pH = 7.0, Pt/base = 0.5) gives four products. Two of them, mononuclear complexes in which platinum is bound to adenosine through N(7) or N(1), comprise more than 90% of all the products. The N(1) and N(7) sites on adenosine indicate almost equal binding affinity for [Pt(NH₃)₃Cl]Cl. The reaction of cis-Pt(NH₃)₂Cl₂ with adenosine has been studied in the presence of a large excess of adenosine (Pt/base ? 0.05). The reaction gives four products. One is the monomeric 2:1 complex with cis-Pt(NH₃)₂²⁺ bound to two adenosine molecules through the N(7) site and the N(1) site, and another is the monomeric 2:1 complex with cis-Pt(NH₃)₂²⁺ bound to two adenosine molecules through the N(7) sites. cis-Pt(NH₃)₂Cl₂ is stronger affinity to the N(7) site than of adenosine to the N(1) site.     

Platinum(II) triammine antitumour complexes: structure-activity relationship with guanosine 5′-monophosphate (5′-GMP)

The multinuclear (¹H, ¹⁵N, ³¹P and ¹⁹⁵Pt) NMR spectroscopies, ES-MS and HPLC have been employed to investigate the structure-activity relationship for the reactions between guanosine 5′-monophosphate (5′-GMP) and the platinum(II)-triamine complexes of the general formulation cis-[Pt(NH₃)₂(Am)Cl]NO₃ (where Am represents a substituted pyridine). The order of reaction rate of the reactions was found to be: 3-phpy > 4-phpy > py > 4-mepy > 3-mepy > 2-mepy. The two basic factors, steric and electronic, were attributed to the order of the binding rate constants. A possible mechanism of the reaction of cis-[Pt(NH₃)₂(Am)Cl]⁺ with 5′-GMP suggested that the reactions proceed via direct nucleophilic attack and no loss of ammonia. cis-[Pt(NH₃)₂(Am)Cl]⁺ binds to the N7 nitrogen of the guanine residue of 5′-GMP to form a coordinate bond with the Pt metal centre. This mechanism is apparently different from that of cisplatin. The pK_a value of cis-[Pt(NH₃)₂(4-mepy)(H₂O)](NO₃)₂ (5.63) has been determined at 298 K by the use of distortionless enhancement by polarization transfer (DEPT) ¹⁵N NMR spectroscopy and compared to the pK_a value of cis-[PtCl(H₂O)(NH₃)₂]⁺.     

Coordination of 9-methyladenine to [cis-Pt(NH3)2]2+ and [Pt(dien)]2+ as studied by proton NMR

Reaction products of 9-methyladenine (mAde) with [Pt(dien)Cl]Cl and cis-Pt(NH₃)₂Cl₂ have been separated using CM-Sephadex C25 cation exchange chromatography. NMR and UV characteristics are presented; the platinum binding sites were established by studying the pH dependence of the ¹H-NMR chemical shifts and of UV difference absorption. It is shown that the N 1 atom of the ligand can be protonated in Pt(mAde-N7) adducts, while the N7 atom can be protonated in Pt(mAde-N1).     

Synthesis and X-ray crystal structure analysis of 1:1 and 1:2 complexes of cisplatin with the model nucleobase 9-methyladenine in its protonated form and a unique HNO3 adduct of cis-[(NH3)2Pt(9-MeAH-N7)2]

The 1:1 and 1:2 complexes of cis-(NH₃)₂Pt^II with 9-methyladeninium cations, 9-MeAH⁺, have been prepared and characterized by X-ray crystallography: cis-[(NH₃)₂Pt(9-MeAH-N7)Cl](NO₃)₂ (1) and cis-[(NH₃)₂Pt(9-MeAH-N7)₂](NO₃)₄ · 2HNO₃ · 2H₂O (2). The pK_a values for 9-MeAH⁺ in H₂O are 1.7 in 1 as well as 0.4 (pK_a1) and 1.3 (pK_a2) for 2, as determined by pD dependent ¹H NMR spectroscopy. Compound 2 is special in that it crystallizes with two equivalents of HNO₃ per Pt entity. The HNO₃ molecules are stacked in rectangular channels provided by cis-(NH₃)₂Pt^II units, 9-methyladeninium ligands and nitrate anions, which form a porous network of hydrogen bonds.     

Study of Pt(II)-cyclic amines complexes of the types cis- and trans-Pt(amine)2I2 and cis- and trans-Pt(amine)2(NO3)2 and their aqueous products by

Complexes of the types cis- and trans-Pt(amine)₂I₂ containing cyclic amines were synthesized and studied mainly by IR and multinuclear NMR spectroscopies. The compounds were converted to cis- and trans-Pt(amine)₂(NO₃)₂, which were also investigated. The hydrolysis and the aquation reactions of the latter compounds were then studied in D₂O in different conditions of pH. In acidic medium, the aqueous product is [Pt(amine)₂(D₂O)₂]²⁺ and for a few amines, [Pt(amine)₂(D₂O)(NO₃)]⁺ was detected. In basic pH, the main product is Pt(amine)₂(OD)₂ and Pt(amine)₂(OD)(NO₃) was detected for several compounds. In neutral pH, the cis isomers form between two and four species in fresh solutions. The most shielded species in ¹⁹⁵Pt NMR is the monoaqua-monohydroxo complex cis-[Pt(amine)₂(D₂O)(OD)]⁺ and the less shielded compound is the dihydroxo-bridged dimer [Pt(amine)₂(μ-OD)₂Pt(amine)₂]²⁺, which were observed for all the compounds. For a few amines, the monohydroxo-bridged dimer [Pt(D₂O)(amine)₂(μ-OD)Pt(OD)(amine)₂]²⁺ was detected and for cyclohexylamine, a fourth signal was assigned to a cyclic hydroxo-bridged trimer [(Pt(amine)₂(μ-OD))₃]³⁺. ¹⁹⁵Pt NMR spectroscopy has shown that the concentration of the monomer decreases with time, while the concentration of the dimers increases. Only one product was observed for the trans isomers in neutral pH. The signal was assigned to the monoaqua-monohydroxo species trans-[Pt(amine)₂(D₂O)(OD)]⁺. The ¹³C and ¹H NMR spectra of most of the complexes were measured. All the coupling constants ^2,3J(¹⁹⁵Pt-¹H) and ^2,3J(¹⁹⁵Pt-¹³C) are larger in the cis compounds than in the trans isomers.     

The structure of a platinum(II) complex of cytidine-3'-monophosphate.

The structure of the cis-[Pt(NH₃)₂(3′-CMP)₂]^2? ion, isolated in a partially protonated form as its cesium salt, has been analyzed by single-crystal x-ray diffraction methods. The 3′-CMP ligands bind in a monodentate fashion through their N(3) atoms: in contrast to the structure of [Pt(en)(5′-CMP)]₂, no covalent platinum-phosphate bonding is found. This compound represents the first example of a 1:2 cis-metal/cytosine complex structurally characterized.     

Synthesis and multinuclear magnetic resonance spectroscopy of the novel ionic Pt(II) mixed-ligands complexes cis- and trans-[Pt(amine)2(pyrimidine)2](NO3)2

Novel ionic mixed-ligands complexes of the types cis- and trans-[Pt(amine)₂(pm)₂](NO₃)₂ (where pm = pyrimidine) were synthesized and studied in the solid state by IR spectroscopy and in aqueous solution by multinuclear (¹⁹⁵Pt, ¹H and ¹³C) magnetic resonance spectroscopy. The results of the solution NMR characterization have shown that the isolated compounds are pure. In ¹⁹⁵Pt NMR, the cis RNH₂ complexes were observed at slightly lower fields (ave. −2441 ppm) than the equivalent trans analogues (ave. −2448 ppm). For Me₂NH, the difference between the two isomers is larger (29 ppm). The complexes are observed at lower fields (difference of 100 ppm) than the corresponding [Pt(amine)₄]²⁺ complexes, which might indicate the presence of π-backdonation in the Pt-pm bond. In ¹H NMR, the coupling constants ³J(¹⁹⁵Pt-¹H_amine) are larger in the cis compounds (38-48 Hz) than in the trans analogues (30-36 Hz). The ³J(¹⁹⁵Pt-¹H_pm) values are also larger for the cis isomers. In ¹³C NMR spectroscopy, the coupling constants ³J(¹⁹⁵Pt-¹³C_amine) are 36 Hz (ave.) for the cis complexes and 26 Hz (ave.) for the trans isomers, while the ²J(¹⁹⁵Pt-¹³C_amine) are 18 Hz (cis) and 14 Hz (trans), respectively. The ³J(¹⁹⁵Pt-¹³C_5(pm)) values are 36 Hz (cis) and 28 Hz (trans). A few ²J(¹⁹⁵Pt-¹³C_pm) couplings were observed (7-10 Hz).     

Synthesis and study of Pt(II)-aromatic amines complexes of the types cis- and trans-Pt(amine)2(NO3)2 and cis-Pt(amine)2(R(COO)2)

Complexes of the types cis- and trans-Pt(amine)₂(NO₃)₂ with amines containing a phenyl group were synthesized and studied mainly by IR and multinuclear magnetic resonance spectroscopies. The cis complexes could be synthesized pure only with the amines of the type Ph-R-NH₂ (R = alkyl), while pure trans compounds were synthesized with all the studied amines. In ¹⁹⁵Pt NMR spectroscopy, the dinitrato complexes of the amines Ph-R-NH₂ were observed around −1700 ppm for the cis isomers and at about −1580 for the trans complexes. For the other amines, where a phenyl ring is directly attached to the amino group, the signals were observed at lower fields, −1528 ppm for cis-Pt(PhNH₂)(NO₃)₂ and around −1450 ppm for all the trans isomers. There is a linear relationship between the δ(Pt) of the Pt(amine)₂(NO₃)₂ complexes and the pK_a of the protonated amines. The coupling constants ²J(¹⁹⁵Pt-¹HN) are larger in the cis compounds (ave. 76 Hz) than in the trans isomers (ave. 63 Hz). The complexes cis-Pt(amine)₂(R(COO)₂) with bidentate dicarboxylato ligands were also synthesized and characterized mainly by IR spectroscopy. The compounds apparently decompose in DMF and are too insoluble in other solvents for solution studies.     

Multinuclear magnetic resonance studies of the reactions of the antitumor complexes cis-Pt(L)2X2 and cis-Pt(NH3)(L)X2 (L = cyclobutylamine and cyclopentylamine) with guanosine and other bases and crystal structures of Pt(cyclopentylamine)2I2

The crystal structures of two Pt(cyclopentylamine)₂I₂ compounds were determined by X-ray diffraction methods. Both crystals contain disordered cyclopentylamine ligands. Crystal I contains two independent trans-Pt(cyclopentylamine)₂I₂ molecules and all the C atoms are disordered on two positions. The second crystal (II) is most interesting since it contains both cis- and trans-Pt(cyclopentylamine)₂I₂ isomers in the same unit cell. It was prepared from the recrystallization of the cis isomer in acetone. The C atoms of the trans molecule in crystal II are disordered on two positions, while only one position was determined in the cis molecule, although some of the C thermal factors are quite high. The reactions of cis-Pt(amine)₂X₂ and cis-Pt(NH₃)(amine)X₂ (amine = cyclobutylamine and cyclopentylamine) with guanosine in water were studied in different Pt:guanosine proportions by multinuclear (¹H, ¹⁹⁵Pt and ¹⁵N) magnetic resonance spectroscopy. The presence of several species in solution was observed. For the mixed-cyclobutylamine compound, ¹⁵N NMR has shown that some of the NH₃ ligands have been displaced from the coordination sphere in the presence of an excess of guanosine. The reactions of the two mixed-ligand complexes cis-Pt(NH₃)(amine)Cl₂ with 9-methylguanine, inosine and 9-methylhypoxanthine were also studied in water and the results are discussed.     

X-ray structure of a mono(1-methylthyminato) complex of cisplatin,chloro-(1-methylthyminato-N3)-cis-diammineplatinum(II) monohydrate

The crystal structure of chloro-(1-methyltyminato- N3)-cis-diammineplatinum(II) monohydrate, cis- (NH₃)₂Pt(C₆H₇N₂O₂)Cl·H₂O, is reported. The compound crystallizes in space group P$\text{1}$ with a = 6.911(2) Å, b = 8.598(3) Å, c = 11.464(4) Å, α = 100.13(3)°, β = 120.03(3)°, γ = 93.16(3)°, Z = 2. The structure was refined to R = 0.048 and R_w = 0.057. The compound contains the deprotonated 1-methylthymine ligand coordinated to Pt through N3 (1.973(10) Å). This distance represents the shortest Pt-N3(pyrimidine-2.4-dione) bond reported so far. The two PtNH₃ bond lengths differ significantly: PtNH₃ (trans to Cl) is longer (2.052(10) Å) than PtNH₃ (trans to N3 of 1-MeT) (2.002(11) Å). The PtCl distance (2.326(3) Å) is normal, as is the large dihedral angle between the Pt coordination plane and the nucleobase (76.5°).     

Multinuclear magnetic resonance study of Pt(II) compounds with sulfoxide ligands and crystal structures of complexes of the types [Pt(R2SO)X3] and Pt(R2SO)2Cl2

Pt(II) complexes of the types K[Pt(R₂SO)X₃], NR₄[Pt(R₂SO)X₃] and Pt(R₂SO)₂Cl₂ (where X = Cl or Br) were characterized by multinuclear magnetic resonance spectroscopy (¹⁹⁵Pt, ¹H and ¹³C). In ¹⁹⁵Pt NMR, the chloro ionic compounds have shown signals between −2979 and −3106 ppm, while the cis disubstituted complexes were observed at higher fields, between −3450 and −3546 ppm. The signal of the compound trans-Pt(DPrSO)₂Cl₂ was found at higher field (−3666 ppm) than its cis analogue (−3517 ppm), since π-back-donation is considerably less effective in the trans geometry. In ¹H NMR, a single signal was observed for the sulfoxide in [Pt(DMSO)Cl₃]⁻, but for the other more sterically hindered ligands, two series of resonances were observed for the protons in α and β positions. The coupling constant ³J(¹⁹⁵Pt-¹H) are between 15 and 33 Hz. The ¹³C NMR results were interpreted in relation to the concept of inversed polarization of the π sulfoxide bond. The ²J(¹⁹⁵Pt-¹³C) values vary between 35 and 66 Hz, while a few ³J(¹⁹⁵Pt-¹³C) couplings were observed (13-26 Hz). The crystal structures of five monosubstituted ionic compounds N(n-Bu)₄[Pt(TMSO)Cl₃], N(Me)₄[Pt(DPrSO)Cl₃], K[Pt(EMSO)Cl₃], K[Pt(TMSO)Br₃] · H₂O and N(Et)₄[Pt(DPrSO)Br₃] and one disubstituted complex cis-Pt(DBuSO)₂Cl₂ were determined. The trans influence of the different ligands is discussed.     

Complex of cis-(NH3)2PtCl2 with guanylyl(3′-5′)-cytidine

The predominant complex formed by the reaction of cis-(NH₃)₂PtCl₂ and guanylyl(3′-5′)cytidine has been isolated. The molar ratio of the binding of cis-(NH₃)₂PtCl₂ to guanylyl(3′-5′)-cytidine is 1:2. The values of proton dissociation constant due to guanine and cytosine bases provide useful information for determining the binding site of the isolated complex. In addition, nmr and ir spectral data were used to determine the binding site. cis-(NH₃)₂PtCl₂ coordinates to guanylyl(3′-5′)cytidine through N(7) position of the guanine base, but cytosine base does not participate in the binding to cis-(NH₃)₂Pt²⁺. Interbase crosslink has not been detected. The binding specificity of cis-(NH₃)₂PtCl₂ to guanine base is discussed.     

Novel palladium(II) and platinum(II) complexes of biocidal benzisothiazolinone (Bit); X-ray crystal structures of co-crystallised Bit/BitO and cis-Pd(en)(Bit−1H)2·H2O

Reaction of benzisothiazolinone (Bit), a well-known biocide, with the Pd(II) and Pt(II) am(m)ine precursors cis-[Pd(en)(H₂O)₂](NO₃)₂ and cis-[Pt(NH₃)₂(H₂O)₂](NO₃)₂ yielded cis-Pd(en)(Bit_−1H)₂ and cis-Pt(NH₃)₂(Bit_−1H)₂, respectively. Bit is bound to the metal centres in both cases through the deprotonated isothiazolinone N. The crystal structures of a Bit/BitO co-crystal and cis-Pd(en)(Bit_−1H)₂·H₂O are also described.     

Chelate ring size and effect of N-substituents as limiting factors for the formation of cationic chloro-diamine-η2-ethene-platinum(II) complexes

The nature of the diamine plays a very critical role in stabilizing the cationic species [Pt(η²-C₂H₄)Cl(diamine)]⁺ containing a highly reactive olefin. Hence while N,N,N′,N′-tetramethyl-1,2-diaminoethane (tmen) gave a species isolatable in a pure form, N,N,N′,N′-tetramethyl-1,3-diaminopropane (tmpm) and unsubstituted 1,2-diaminoethane (en) were unable to act as bidentate and gave, as isolatable species, only complexes of the type cis-[Pt(η²-C²H⁴)Cl²(Hdiamine)]⁺ in which the diamine is protonated and acts as monodentate towards platinum. These results are explained in terms of greater conformational stability of five- versus six-membered chelate rings and of gem-dimethyl substituted towards unsubstituted ring systems (Thorpe-Ingold effect).     

FT-IR and 1H NMR spectroscopic evidence of sugar ring conformational change in NH4GpG on complexation to form cis-[Pt(NH3)2(GpG)]+

The conformational change of the ribose ring in NH₄GpG and cis-[Pt(NH₃)₂(GpG)]⁺ was confirmed by FT-IR spectroscopic evidence as being C2′-endo, C3′-endo, anti, gg sugar ring pucker in the solid state. These results were compared with ¹H NMR spectral data in aqueous solution. The FT-IR spectrum of NH₄GpG shows marker bands at 802 cm^?1 and 797 cm^?1 which are assigned to the C3′-endo, anti, gg sugar-phosphate vibrations of ribose (?pG) and ribose (Gp?), respectively. The FT-IR spectrum of cis-[Pt(NH₃)₂(GpG)]⁺ (with N7N7 chelation in the GpG sequence) shows a marker band at 800 cm^?1 which is assigned to the C3′-endo, and a new shoulder band at 820 cm^?1 related to a C2′-endo ring pucker. The ribose conformation of (?pG) moiety in NH₄-GpG, C3′-endo, anti, gg changes into C2′-endo, anti, gg when a platinum atom is chelated to N7N7 in the GpG sequence.     

Trichloroamine complexes of platinum: preparation,crystal structure and solution behavior of cytosinium trichlorocytosineplatinate(II)

A complex containing a protonated and N3-platinated cytosine (C), [CH][Cl₃Pt(C)] (1a) has been prepared, converted into its K[Cl₃Pt(C)] (1b) and NH₄[Cl₃]Pt(C)]·H₂O (1c) analogs, and structurally characterized (X-ray, Raman, NMR). Reaction of 1b with L = 1-methylcytosine and with L = Me₂SO gave the neutral mixed-ligand complexes cis-Cl₂Pt(C)L. Excess NH₃ was used to convert the anion of 1b into the cation [(NH₃)₃Pt(C)]²⁺ (3a). The pK_a of the N(1)H proton in 3a is 9.4, as determined by UV spectroscopy. The N(1)H is displaced by Pt(II) electrophiles even at neutral pH to give N3,N1-diplatinated cytosinato complexes, as shown by ¹H NMR (³J coupling or ¹⁹⁵Pt at N(1) with H6, 29 Hz, and ⁴J coupling of ¹⁹⁵Pt at N(3) with H5, 14Hz). The results of the X-ray structure determination of 1a (R = 0.031, R_w = 0.034) are of relevance in that they permit a direct comparison of the effect of a proton as opposed to that of a Pt electrophile on the nucleobase geometry. Moreover, the expected decrease in CO(2) bond length as a consequence of Pt binding is observed.     

NMR studies of the interaction of cis-diamminedichloro-platinum(II) and corresponding hydrolysis products with adenosine phosphates

Complexes formed in aqueous solution between cisplatin or hydrolysis species and 5′ adenosine monophosphate (AMP) or 5′ adenosine triphosphate (ATP), the latter with and without chloride ions, have been determined using ¹⁹⁵Pt, ³¹P, ¹³C and ¹H NMR. The present results lead to the conclusion that the only monodentate complexes with AMP are cis-Pt(NH₃)₂(AMP-N7)Cl at acid pH and cis-Pt(NH₃)₂(AMP-N7)OH at neutral and basic pH. Other bidentate complexes were identified as cis-Pt(NH₃)₂(AMP-N7)₂ and cis-Pt(NH₃)₂(AMP-N7)(AMP-PO). Also discussed herein are the binding of platinum to the phosphate group Pγ with ATP and at acid pH, and the formation of the [cis-Pt(NH₃)₂(ATP-N7)H₂O]⁺ complex. In neutral and basic pH ranges, the phosphate moiety of ATP is the most reactive site. In the presence of an excess of chloride ions, the complexation rates between the ATP and the cisplatin are decreased. Furthermore, in the experimental conditions used neither the ATP nor the AMP have shown binding to N1.     

Synthesis and characterization of cis-[(PPh3)2Pt{9-MeAd(-H),NN}]X (X = NO3, PF6): The first example of a platinum(II) complex containing the N,N-chelated 9-methyladenine anion

Reaction between the binuclear hydroxo complex cis-[(PPh₃)₂Pt(μ-OH)]₂X₂ (X⁻ = NO₃, 1a; , 1b) and the model DNA base 9-methyladenine (9-MeAd) leads to the formation of the mononuclear species cis-[(PPh₃)₂Pt{9-MeAd(-H),N⁶N⁷}]X (X⁻ = NO₃, 2a; PF₆, 2b), in which the nucleobase chelates the Pt(II) ion with the N6 and N7 atoms. The coordination mode of the nucleobase has been determinated through a multinuclear (¹H, ³¹P, ¹³C, ¹⁵N and ¹⁹⁵Pt) NMR analysis and the nuclearity of the complex has been obtained by E.S.I. mass spectrometry. 2 represents the first example of an isolated platinum complex in which the NH₂-deprotonated adenine exhibits this binding mode.     

Studies on the reactions of PtCl2en,cis-Pt(NH3)2Cl2 and their aqua species with adenosine,deoxyadenosine and adenine using ion-pair HPLC

The reactions of PtCl₂en or cis-Pt(NH₃)₂Cl₂ and their aqua species with adenine and adenosine were studied by means of ion-pair HPLC. From the chromatograms, it was found that the first binding site of Pt(II) was the N(7) site of adenine under both acidic and neutral conditions. The rates of Pt(II) binding at the (N7) site of adenosine and deoxyadenosine were measured. The rate constants, k₁, were obtained for the reactions of PtCl₂en or cis-Pt(NH₃)₂Cl₂ with adenosine and deoxyadenosine at pH 3 and 7 over the temperature range 9–25 °C. The k₁ values were 6.8–7.7 × 10⁻⁴ dm³ mol⁻¹ s⁻¹ at 25 °C. For the aqua species, the rate of [cis-Pt(NH₃)₂ClH₂O]⁺ with adenosine N(7) was measured. The rate constants, k₂ which were found to be smaller than those of hydrolysis, k_h, were calculated at pH 3 over the temperature range 25–40 °C. The k₂ value obtained at 25 °C was 1.1 × 10⁻² dm³ mol⁻¹ s⁻¹, 15 time larger than k¹. The activation parameters were also calculated.     

Stabilisation of the iminooxo tautomer of 1-methylcytosine in Pt complexes: Role of the ancillary ligands

Reaction of cis-[L₂Pt(μ-OH)]₂(NO₃)₂ (L = PPh₃) with 1-methylthymine (1-MeTy), in DMF, leads to the formation of the mononuclear neutral adduct cis-L₂Pt{1-MeTy(-H)}(ONO₂) (1) whose structure in the solid state has been obtained by single crystal X-ray diffraction. The deprotonated nucleobase is bounded at the N(3) site, with the pyrimidinic ring almost perpendicular (78.0(1)°) to the metal coordination plane. The fourth ligand is a monodentate nitrate group. Addition of 1 equiv. of 1-methylcytosine (1-MeCy) causes the immediate replacement of the nitrato ligand to form the cationic complex cis-[L₂Pt{1-MeTy(-H)}(1-MeCy,N³)]NO₃ (2) in which both the nucleobases are N(3)-platinated. In CD₂Cl₂ at −40 °C 2 exists as a mixture of two conformers (2:1 molar ratio) arising from the different orientation of the nucleobases with respect to the metal coordination plane.In solution of DMSO, DMF or chlorinated solvents, 2 slowly converts into the isomer cis-[L₂Pt{1-MeTy(-H)}(1-MeCy,N⁴)]NO₃ (3), containing the tautomeric form of the cytosine stabilised through the coordination at the N(4) atom, as a mixture of conformers whose relative abundance is dependent on the solvent and the temperature.In contrast, the analogous complex of 2 containing the phosphine PMe₃, cis-[(PMe₃)₂Pt{1-MeTy(-H)}(1-MeCy,N³)]NO₃ (4), also isolated as pure compound, in DMSO solution slowly rearranges leading to the elimination of the neutral 1-MeTy, with the formation of the dinuclear cytosinate complex cis-[(PMe₃)₂Pt{1-MeCy(-H),N³N⁴}]₂(NO₃)₂, previously characterised by us.