Synthesis and structures of novel 1-methylcytosinato-bridged (ethylenediamine)platinum(ii) and platinum(<scp>iii</scp>) dinuclear complexes

Lippert

2011

Pyrimidine (pym) ligands with their two endocyclic N-donor atoms provide 120° angles for molecular constructs, which, with the 90° angle metal fragments cis-a(2)M(II) (M=Pt, Pd; a=NH(3) or a(2)=diamine), form cyclic complexes known as metallacalix[n]arenes (with n=3, 4, 6, 8, …). The number of possible isomers of these species depends on the symmetry of the pym ligand. Although highly symmetrical (C(2v)) pym ligands form a single linkage isomer for any n and can adopt different conformations (e.g., cone, partial cone, 1,3-alternate, and 1,2-alternate in the case of n=4), low-symmetry pym ligands (C(s)) can produce a higher number of linkage isomers (e.g., four in the case of n=4) and a large number of different conformers. In the absence of any self-sorting bias, the number of possible species derived from a self-assembly process between cis-a(2)M(II) and a C(s)-symmetrical pym ligand can thus be very high. By using the C(s)-symmetric pym nucleobase cytosine, we have demonstrated that the number of feasible isomers for n=4 can be reduced to one by applying preformed building blocks such as cis-[a(2)M(cytosine-N3)(2)](n+) or cis-[a(2)M(cytosinate-N1)(2)] (for the latter, see the accompanying paper: A. Khutia, P. J. Sanz Miguel, B. Lippert, Chem. Eur. J. 2011, 17, DOI: 10.1002/chem.2010002723) and treating them with additional cis-a(2)M(II) . Moreover, intramolecular hydrogen-bonding interactions between the O2 and N4H(2) sites of the cytosine ligands reduce the number of possible rotamers to one. This approach of the "directed" assembly of a defined metallacalix[4]arene is demonstrated.

Section: Hemi-deprotonated and Fully Deprotonated Derivatives Ofmentioning

confidence: 57%

“Directed” Assembly of Metallacalix[n]arenes with Pyrimidine Nucleobase Ligands of Low Symmetry: Metallacalix[n]arene Derivatives ofcis‐[a₂M(cytosine‐N3)₂]²⁺(M=Pt^II, Pd^II;n=4 and 6)

Khutia

Lippert

2011

“…The situation thus is similar to that seen in the reaction of compound 7 with the amino acid glycine, which also yields a diplatinum(III) product with the carboxylate O atom bonded in plane and the amino group positioned in the apical position 9. It differs from the situation seen in the asymmetrical diplatinum(III) complex h , t ‐[(H 2 O)(en)Pt(1‐MeC − ) 2 Pt(en)(OH)](ClO 4 ) 3 ,42 in which one of the two en ligands chelates in a mixed apical/equatorial fashion, with the hydroxido ligand at one of the two Pt ions is trans to the N3 atom of 1‐MeC − , however. The water molecule at the second Pt is in axial position.…”

Section: Resultsmentioning

confidence: 95%

“…Salient structural features are as follows: Both metal ions are hexa‐coordinated and are connected by a short PtPt bond. The bond lengths of 2.5406(6) Å makes it the second shortest bond in diplatinum(III) complexes containing bridging 1‐methylcytosinato ligands,9, 41, 42 surpassed only by the complex with chelating glycinato ligands at either end of the dinuclear cation 9. Apart from the PtPt bond lengths, there are several additional differences between compound 9 on one hand and the diplatinum(III) complexes containing equatorial NH 3 or ethylenediamine (en) ligands on the other hand.…”

Section: Resultsmentioning

confidence: 99%

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

Siebel

Dammann

et al. 2015

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.

“…Its assignment is based on the rather similar 1 H NMR chemical shifts of its 1‐MeC ‐H resonances with those of the species “ X ” in the corresponding Pt,Pd systems . The way of the formation of compound 1 a′′′ used here, is thus an alternative to its synthesis through the reaction of the cis‐ [(NH 3 ) 2 Pt(OH) 2 Pt(NH 3 ) 2 ] 2+ species, which is the route commonly pursued to produce dinuclear Pt complexes containing a single hydroxide bridge and a single bridge of a heterocyclic ligand …”

Section: Resultsmentioning

confidence: 98%

“…We have used these compounds as precursor for the synthesis of bis(nucleobase) or mixed nucleobase/amino acid species as possible models for DNA or DNA/protein adducts of the antitumor agent cisplatin, for the preparation of the head–tail dinuclear 1‐methylcytosinato complex cis‐ [{Pt(NH 3 ) 2 (1‐MeC ‐H ‐N3,N4)} 2 ] 2+ ( 1 c ), and their diplatinum(III) oxidation products, and finally also for the synthesis of tris(nucleobase) complexes of Pt II . More recently, some basic coordination chemistry of the analogous complex [Pt(en)(1‐MeC‐N3)Cl]NO 3 has been reported by the group of Keppler et al . Interestingly, the closely related complex cis‐ [Pt(NH 3 ) 2 (C‐N3)Cl] + , with C being the unsubstituted parent nucleobase cytosine, proved to be the first monofunctional, cationic Pt II complex to show pronounced antitumor activity…”

Section: Resultsmentioning

confidence: 99%

Multiple Condensation Reactions Involving Pt^II/Pd^II−OH₂, Pt−NH₃, and Cytosine−NH₂ Groups: New Twists in Cisplatin−Nucleobase Chemistry

Yin-Bandur

Rodrı́guez-Santiago

et al. 2016

The coordination chemistry of the antitumor agent cisplatin and related complexes with DNA and its constituents, that is, the nucleobases, appears to be dominated by 1:1 and 1:2 adducts of the types cis-[Pta2 (nucleobase)X] and cis-[Pta2 (nucleobase)2 ] (a=NH3 or amine; a2 =diamine or diimine; X=Cl, OH or OH2 ). Here, we have studied the interactions of the putative 1:1 adducts cis-[Pta2 (1-MeC-N3)(OH2 )](2+) (with a=NH3 , a2 =2,2'-bpy (2,2'-bipyridine), 1-MeC=model nucleobase 1-methylcytosine) with additional cis-[Pt(NH3 )2 (OH2 )2 ](2+) or its kinetically superior analogues [Pd(en)(OH2 )2 ](2+) (en=ethylenediamine) and [Pd(2,2'-bpy)(OH2 )2 ](2+) . Depending upon the conditions applied different compounds of different nuclearity are formed. Without exception they represent condensation products of the components, containing μ-1-MeC-H , μ-OH(-) , as well as μ-NH2 (-) bridges. In the presence of Ag(+) ions, the isolated products in several cases display additionally Pt→Ag dative bonds. On the basis of the cytosine-containing structures established by X-ray crystallography, it is proposed that any of the feasible initial 1:1 nucleobase adducts of cisplatin could form dinuclear Pt complexes upon reaction with additional hydrolyzed cisplatin, thereby generating nucleobase adducts other than the presently established ones. Two findings appear to be of particular significance: First, hydrolyzed cisplatin can have a moderately accelerating effect on the formation of a secondary nucleobase product. Second, NH3 ligands of the cisplatin moiety can be converted into bridging amido ligands following condensation with the diaqua species of cisplatin.