Platinum(II)-Mediated Coupling Reactions of Acetonitrile with the Exocyclic Nitrogen of 9-Methyladenine and 1-Methylcytosine. Synthesis, NMR Characterization, and X-ray Structures of New Azametallacycle Complexes

Abstract

The hydroxo complex cis-[L 2 Pt(µ-OH)] 2 (NO 3 ) 2 , (L ) PMePh 2 , 1a), in CH 3 CN solution, deprotonates the NH 2 group of 9-methyladenine (9-MeAd) to give the cyclic trinuclear species cis-[L 2 Pt{9-MeAd(−H)}] 3 (NO 3 ) 3 , (L ) PMePh 2 , 2a), in which the nucleobase binds the metal centers through the N(1), N(6) atoms. In solution at room temperature, 2a slowly reacts with the solvent to form quantitatively the mononuclear azametallacycle cis-[L 2 PtNHdC(Me){9-MeAd(−2H)}]NO 3 (L ) PMePh 2 , 3a), containing as anionic ligand the deprotonated form of molecule N-(9-methyl-1,9-dihydro-purin-6-ylidene)-acetamidine. In the same experimental conditions, the hydroxo complex with PPh 3 (1b) forms immediately the insertion product 3b. Single-crystal X-ray analyses of 3a and 3b show the coordination of the platinum cation at the N(1) site of the purine moiety and to the N atom of the inserted acetonitrile, whereas the exocyclic amino nitrogen binds the carbon atom of the same CN group. The resulting six-membered ring is slightly distorted from planarity, with carbon−nitrogen bond distances for the inserted nitrile typical of a double bond [C(3)− N(2) ) 1.292(7) Å in 3a and 1.279(11) Å in 3b], while the remaining CN bonds of the metallocycle are in the range of 1.335(8)−1.397(10) Å. A detailed multinuclear 1 H, 31 P, 13 C, and 15 N NMR study shows that the nitrogen atom of the inserted acetonitrile molecule binds a proton suggesting for 3a,b an imino structure in solution. In DMSO and chlorinated solvents, 3a slowly releases the nitrile reforming the trinuclear species 2a, whereas 3b forms the mononuclear derivative cis-[L 2 Pt{9-MeAd(−H)}]NO 3 (L ) PPh 3 , 4b), in which the adeninate ion chelates the metal center through the N(6) and N(7) atoms. Complex 4b is quantitatively obtained when 1b reacts with 9-MeAd in DMSO and can be easily isolated if the reaction is carried out in CH 2 Cl 2 . In CH 3 CN solution, at room temperature, 4b slowly converts into 3b indicating that the insertion of acetonitrile is a reversible process. A similar metalmediated coupling reaction occurs when 1a,b react with 1-methylcytosine (1-MeCy) in CH 3 CN. The resulting complexes, cis-[L 2 PtNHdC(Me){1-MeCy(−2H)}]NO 3 , (L ) PMePh 2 , 5a and PPh 3 , 5b), contain the deprotonated form of the ligand N-(1-methyl-2-oxo-2,3-dihydro-1H-pyrimidin-4-ylidene)-acetamidine. The X-ray analysis of 5a shows the coordination of the metal at the N(3) site of the pyrimidine cycle and to the nitrogen atom of the acetonitrile, with features of the six-membered metallocycle only slightly different from those found in 3a and 3b. In CD 3 CN/ CH 3 13 CN solution complexes 5a,b undergo exchange of the inserted nitrile, while in DMSO or chlorinated solvents they irreversibly release CH 3 CN to form species not yet fully characterized. No insertion of CH 3 CN occurs when the hydroxo complexes are stabilized by PMe 3 and PMe 2 Ph.

Synthesis, characterization and cytotoxic properties of platinum(II) complexes containing the nucleosides adenosine and cytidine

“…The 1 H and 31 P NMR data are very similar to those exhibited by the nucleobase analogs [20,21], cis-[(PPh 3 ) 2 PtNH=C(R){1-MeCy (−2H)}]NO 3 (R = Me, 7a: R = Ph, 7b), cis-[(PPh 3 ) 2 PtNH=C(R){9-MeAd(−2H)}]NO 3 (R = Me, 8a: R = Ph, 8b) previously characterized. In Table 2 selected 31 P and 1 H NMR of these complexes are collected.…”

“…Adenosine, cytidine and all the solvents (MeOH, Et 2 O, PhCN, CH 3 [20], cis-[(PMe 3 ) 2 Pt(μ-OH)] 2 (NO 3 ) 2 [22], cis-[(PPh 3 ) 2 PtHN=C(Me){1-MeCy(−2H)}]NO 3 (7a) [20], cis-[(PPh 3 ) 2 PtHN=C(Ph){1-MeCy(−2H)}]NO 3 (7b) [21], cis-[(PPh 3 ) 2 PtHN=C(Me) {9-MeAd(−2H)}]NO 3 (8a) [20], cis-[(PPh 3 ) 2 PtHN=C(Me){9-MeAd (−2H)}]NO 3 (8b) [21] were synthesized as previously reported.…”

“…As an example, the reaction of the hydroxo complex cis-[L 2 Pt(μ-OH)] 2 (NO 3 ) 2 with 1-methylcytosine (1-MeCy) causes the deprotonation of the nucleobase leading to cis-[L 2 Pt{μ-1-MeCy(−H),N 3 ,N 4 }] 3 (NO 3 ) 3 when L is PMe 3 [18] and to the mononuclear complex cis-[L 2 Pt{1-MeCy(−H),N 4 } (1-MeCy,N 3 )]NO 3 with L = PPh 3 [19]. In addition, the trinuclear species is stable in solution of nitriles (MeCN, PhCN), whereas the mononuclear species reacts with the solvent to give the amidine derivatives cis-[(PPh 3 ) 2 PtNH=C(R){1-MeCy(−2H)}]NO 3 (R=Me, Ph) [20,21].…”

Synthesis and characterization of cis-[(PPh3)2Pt{9-MeAd(-H),N6N7}]X (X−= NO3, PF6): The first example of a platinum(II) complex containing the N6,N7-chelated 9-methyladenine anion

“…More recently, we reported the structural characterization of the azametallacycle cis-[L 2 PtNH@C(Me){9-MeAd(-2H)}] + (L = PPh 3 ) depicted in Chart 1 [8]. This acetamidine complex releases in chlorinated solvents the inserted CH 3 characterization of this complex, isolated as nitrate (2a) and hexafluorophosphate (2b) salts.…”

Solvent Effects on Nitrogen Chemical Shifts

“…Pt(II) complexes with nitrogen donors trans to Cl have smaller jΔ 15N coord j than those having nitrogen trans to another nitrogen, reflecting the trans effect. Pt(II) complexes of phosphorous-containing trans ligands coordinate either at the pyrimidinic N1 or at the pyrazolic N7 [110,[113][114][115][116]. The jΔ 15N coord j of these complexes are in the range of $50-65 ppm, suggesting the nitrogen donor to be in trans to phosphorous.…”