Iwona Łakomska

The X-ray structure and spectroscopy of platinum(II) complexes with 1,2,4-triazolo[1,5-a]pyrimidines and dimethylsulfoxide

Abstract Platinum(II) complexes with 1,2,4-triazolo[1,5-a]pyrimidines of general formula trans-[PtCl2(dmso)(L)], where L=1,2,4-triazolo[1,5-a]pyrimidine (tp), 5,7-dimethyl-1,2,4-triazolo[1,5-a]pyrimidine (dmtp), 5,7-diphenyl-1,2,4-triazolo[1,5-a]pyrimidine (dptp), 5,7-ditertbutyl-1,2,4-triazolo[1,5-a]pyrimidine (dbtp) have been prepared by direct reaction between cis-[PtCl2(dmso)2] and respective 1,2,4-triazolo[1,5-a]pyrimidine in molar ratio M:L=1:1. All new platinum(II) compounds were characterized by 1H, 13C, 15N, 195Pt NMR and IR. Significant 15N NMR upfield shifts (75–87 ppm) were observed for N(3) atom indicating this nitrogen atom as a coordination site. Crystal structure of trans-[PtCl2(dmso)(dmtp)] (2) has been determinated. The molecular structure indicates that Pt(II) ion has the square-planar geometry with N(3) bonded dmtp, S-bonded dimethylsulfoxide and two trans chloride anions.

Synthesis, characterization and antitumor properties of two highly cytotoxic ruthenium(III) complexes with bulky triazolopyrimidine ligands

Two ruthenium(III) complexes composed of 5,7-ditertbutyl-1,2,4-triazolo[1,5-a]pyrimidine (dbtp) ligands were prepared and structurally characterized by X-ray crystallography, IR, UV-Vis, EPR spectroscopies and cyclic voltammetry (CV). The crystal structures of trans-[RuCl(3)(H(2)O)(dbtp)(2)] 1 and mer-[RuCl(3)(dbtp)(3)]·0.815OCMe(2) 2 showed slightly distorted octahedral geometries with two 1 or three 2 monodentate dbtp ligands bound in a head-to-head orientation. In both complexes, the heterocyclic dbtp ligands were bound to the ruthenium(III) ion through the N3 nitrogen atom. A cytotoxicity assay of both ruthenium(III) compounds against two human cell lines (A549 - non-small cell lung carcinoma and T47D - breast carcinoma) was performed. The ruthenium(III) complexes showed excellent cytotoxicity with IC(50) values in the range of 0.02-2.4 μM against both cancer cell lines. In addition, the in vitro cytotoxic values of the ruthenium(III) compounds were 35-times for 1 and 172-times for 2 higher against T47D than the clinically used antitumor drug cisplatin.

Cytotoxic malonate platinum(II) complexes with 1,2,4-triazolo(1,5-a) pyrimidine derivatives: Structural characterization and mechanism of the suppression of tumor cell growth

A series of malonate (mal) platinum(II) complexes of the general formula [Pt(mal)(L)2], where L=5,7-dimethyl-1,2,4-triazolo[1,5-a]pyrimidine (dmtp) (1), 7-isobutyl-5-methyl-1,2,4-triazolo[1,5-a]pyrimidine (ibmtp) (2) or 5,7-ditertbutyl-1,2,4-triazolo[1,5-a]pyrimidine (dbtp) (3), has been prepared and characterized using multinuclear ((1)H, (13)C, (15)N, (195)Pt) NMR, IR and electrospray ionization mass spectrometry (ESIMS). Furthermore, the crystal structures of [Pt(mal)(dmtp)2]∙4H2O (1a) and [Pt(mal)(dbtp)2]∙CHCl3 (3a) have been determined using single-crystal X-ray diffraction. The spectroscopic characterization unambiguously confirmed the square-planar geometry of Pt(II) with two monodentate N3-bonded 5,7-disubstituted-1,2,4-triazolo[1,5-a]pyrimidines and one O-chelating malonate. The antiproliferative activities of the compounds against the human cell lines T47D (cisplatin-resistant human ductal breast epithelial tumor cell line) and A549 (lung adenocarcinoma epithelial cell line) and the mouse cell line 4T1 (mouse breast tumor model) were assessed using an in vitro screening assay. Compounds (2) and (3) exhibited substantial antigrowth properties against T47D cells, whereas only (3) exhibited an IC50 value that was lower than cisplatin and carboplatin against the 4T1 cell line. Additionally, compounds (2, 3) are capable of arresting the cell cycle of A549 cells at the G0/G1 phase, whereas cisplatin and carboplatin arrested the cells at the G2/M phase, indicating differences in the mechanism of the suppression of tumor cell growth. Finally, in the quest for low toxicity platinum drugs, the in vitro antiproliferative activity against normal mouse fibroblast cells (BALB/3T3) was evaluated. The inhibition of BALB/3T3 cell proliferation by the evaluated Pt(II) complexes increased in the order (1)<(2)<<carboplatin<<(3)

Structure-cytotoxicity relationship for different types of mononuclear platinum(II) complexes with 5,7-ditertbutyl-1,2,4-triazolo[1,5-a]pyrimidine.

To compare the in vitro cytotoxicity of platinum(II) complexes with 5,7-ditertbutyl-1,2,4-triazolo[1,5-a]pyrimidine (dbtp), three complexes were prepared: cis-[PtI(2)(dbtp)(2)] (1), cis-[Pt(NO(3))(2)(dbtp)(2)] (2) and cis-[Pt(C(4)H(4)O(5))(dbtp)(2)] (3). The coordination compounds have been structurally characterized by IR; (1)H, (13)C, (15)N, (195)Pt NMR and single-crystal X-ray diffraction (1). Spectroscopic studies reveal the monodentate coordination of the heterocycle ligand (dbtp) via N(3) to platinum(II) ions. In addition, the crystal structure of (1) shows that the platinum(II) ion is located in nearly square-planar PtI(2)N(2) environments with two heterocycle ligands (dbtp) arranged in a head-to-head orientation. The complexes have been screened for their cytotoxicity against two human cells: non-small cell lung carcinoma (A549) and breast cancer (T47D). All of the complexes demonstrated a significant antiproliferative activity against both cell lines. On the basis of these results, it is concluded that the cytotoxicity of the studied compounds against T47D follows the order: (3)<(1)<(2).

Thermal and spectroscopic studies of the Ag(I) salts with fluorinated carboxylic and sulfonic acid residues

Abstract Silver(I) salts with RCOOH, where R is CF 3 CF 2 ) 2 , CF 3 (CF 2 ) 6 , CF 3 (CF 2 ) 8 C 6 F 5 , C 6 F 5 CH 2 , with RSO 3 H, where R is CF 3 , CF 3 (CF 2 ) 3 , and with HOOC(CF 2 ) 3 COOH were synthesized. The thermal decomposition processes were studied and the activation energies calculated from thermal data. The decomposition mechanisms and thermal stabilities are discussed. From the IR, and 13 C and 19 F NMR measurements, it is proposed that the carboxylic acid residues have monodentate bonding.

Platinum(II) complexes with 5,7-disubstituted-1,2,4-triazolo [1,5-a]pyrimidines: spectroscopical characterization and cytotoxic activity in vitro.

Complexes of the types: cis-[PtI(2)(dptp)(2)] (1), cis-[PtI(2)(NH(3))(dptp)] (2), trans-[PtI(2)(dptp)(dmso)] (3) and trans-[PtI(2)(dbtp)(dmso)] (4), where dptp=5,7-diphenyl-1,2,4-triazolo[1,5-a]pyrimidine (dptp), dbtp=5,7-ditertbutyl-1,2,4-triazolo[1,5-a]pyrimidine have been synthesized and characterized by infrared and multinuclear magnetic resonance spectroscopic techniques ((1)H, (13)C, (15)N, (195)Pt). In (195)Pt NMR, the cis-diiodo complexes were observed between -2601 ppm and -3261 ppm, while the trans coordination compounds were found at higher field (ca. -4389 ppm). In all cases significant (15)N NMR shielding (92-95 ppm) were observed for N(3) atom indicating this nitrogen atom as a coordination site. The cis complexes have been assayed for antitumor activity in vitro against two human cell lines: A549 (non-small cell lung carcinoma) and T47D (breast cancer). The results indicate a moderate antiproliferative activity of (2) against human cancer lines.

Acetate platinum(II) compound with 5,7-ditertbutyl-1,2,4-triazolo[1,5-a]pyrimidine that overcomes cisplatin resistance: structural characterization, in vitro cytotoxicity, and kinetic studies

The reaction of silver acetate with cis-[PtI2(dbtp)2], where dbtp = 5,7-ditertbutyl-1,2,4-triazolo-[1,5-a]pyrimidine, yielded cis-[Pt(OOCCH3)2(dbtp)2]·dmf (1). The complex has been analyzed by multinuclear magnetic resonance (1H, 13C, 15N), IR, and Raman. The compound formed two rotamers in CDCl3 and its spatial structures have been optimized using computational calculation. It was found that head-to-tail rotamer (1a) is more stable than its head-to-head counterpart (1b). In vitro antiproliferative activity against four tumor cell lines (A549, T47D, FaDu, and A2780cis) revealed in all cases significant cytotoxicity (IC50 = 0.26–1.80 μM), possessing IC50 values at least fivefold lower than cisplatin, carboplatin, and oxaliplatin (except A2780cis). The remarkable in vitro activity against T47D and A2780cis suggested the ability to overcome cisplatin resistance in these types of tumor cells. In addition, in vitro toxicity was evaluated against BALB/3T3 and has shown that the lipophilic platinum(II) complex (1) inhibits cell proliferation weaker than cisplatin and oxaliplatin. Additionally, cis-[Pt(OOCCH3)2(dbtp)2]·dmf exhibited selective activity, in contrast to cisplatin or oxaliplatin. Graphical abstract

The bonding of ribavirin to platinum(II) ion.: The X-ray and spectroscopy of Pt(II) complexes with 1-β-d-ribofuranosyl-1,2,4-triazole-3-carboxamide and dimethylsulfoxide

Abstract A platinum(II) complex with 1-β- d -ribofuranosyl-1,2,4-triazole-3-carboxamide is obtained and characterised spectroscopically with 1H, 13C, 15N, 195Pt NMR and IR. Significant 15N NMR coordination shifts (−92.7 and +18.4 ppm) were observed, respectively for N(4) and N(7) indicating these nitrogen atoms as a metallation sites. The X-ray crystal structures of two hydrates [PtCl(dmso)(N4N7-rib)]·H2O (1) and [PtCl(dmso)(N4N7-rib)]·2H2O (2) have been solved. Both complexes revealed square-planar coordination geometry for the Pt atoms with chelate ribavirin, S-bonded dimethylsulfoxide and chloride anion, the distances being as follows: PtN(4) 2.009(4), PtN(7) 2.041(4), PtS 2.218(1), PtCl 2.304(1) A for 1 and PtN(4) 2.032(7), PtN(7) 2.028(7), PtS 2.212(2), PtCl 2.290(2) A for 2.

1H{15N} heteronuclear correlation and 15N cross-polarized magic angle spinning NMR studies of the coordination modes in Zn(II) chloride complexes with purine and methylpurines

Abstract The 1 H{ 15 N} heteronuclear correlation and 15 N cross-polarized magic angle spinning NMR spectra of purine ( 1 ) were measured. The Zn(II) chloride complexes with 1 , 7-methylpurine ( 2 ) and 9-methylpurine ( 3 ) were synthesised and studied by analytical methods, far-IR and 15 N NMR. The formulae of ZnL 2 Cl 2 (L= 1 ) and [ZnLCl 2 ] n (L= 2 , 3 ) were found. The formation of Zn(II)N coordination bonds resulted in 3–15 ppm low-frequency shifts of the respective 15 N NMR signals: N-7 for 1 ; N-1, N-9 for 2 ; N-1, N-7 for 3 .

Thermal studies of Ag(I) complexes with triethylphosphine and perfluorinated carboxylates

Abstract Silver(I) complexes with triethylphosphine and perfluorinated carboxylic acids residues of general formula [Et 3 PAgOOCR] 2 , where R=C 2 F 5 , C 3 F 7 , C 6 F 13 , C 7 F 15 , C 8 F 17 , C 9 F 19 , C 6 F 5 and Et 3 PAgOOC(CF 2 ) 3 COOAgPEt 3 , were synthesized. Thermal decomposition proceeded in two stages – both exothermic processes corresponding to the elimination of carboxylate and triethylphosphine residues. The final product of the thermal decomposition was metallic silver. Analyses by 13 C, 19 F, 31 P NMR spectroscopy and vibrational spectra suggest trigonal coordination of Ag(I), the coordination sphere consisting of unidentate triethylphosphine and bidentate carboxylates forming bridges between metal ions.