cis-[PtCl2(NH3){2-(2-hydroxyethyl)pyridine}] − an Analogue of the Anticancer Drug AMD473: Unusual Hydrolysis Rates and pKa Values for the Diaqua Adduct

Hotze, Anna C. G.; Chen, Yu; Hambley, Trevor W.; Parsons, Simon; Kratochwil, Nicole A.; Parkinson, John; Munk, Vivienne P.; Sadler, Peter J.

doi:10.1002/1099-0682(200205)2002:5<1035::aid-ejic1035>3.0.co;2-i

Cited by 28 publications

(13 citation statements)

References 17 publications

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“…Although the aqua ligand trans to the 1‐MeC ligand can be expected to be slightly more acidic than the one trans to the NH 3 ligand,8b differences in the p K a values of the two species 2 a and 2 a′ cannot be expected to be readily seen in the 1 H NMR spectra, as they represent tautomers 13. The pD value‐dependent 1 H NMR spectra of compound 2 in the range δ =1.8–8.0 ppm reveal the following: The 1‐MeC resonances of compound 2 (i.e., species 2 a and 2 a′ ) display virtually no pD value dependence in the range mentioned.…”

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

Miguel

et al. 2015

Chemistry A European J

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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.

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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

Miguel

et al. 2015

Chemistry A European J

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“…Addition of a primary amine to commercially available 2-pyridinecarboxaldehyde affords the corresponding pyridin-2-ylcarboxaldimine ligand in high yield (11)(12)(13)(14)(15)(16)(17)(18)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31). Variation of the amine allows for the facile design of ligands and platinum complexes with different physical and chemical properties.…”

Section: Resultsmentioning

confidence: 67%

“…1) shows considerable cytotoxicity in cisplatin-resistant cell lines (15,16). Steric crowding from the methyl group is believed to decrease the rates of hydrolysis and substitution reactions of AMD473 thereby permitting high selectivity in binding with DNA (17). Toward this goal, we have begun to develop AMD473 analogues by replacing the NH 3 group with a pendant imine group.…”

Section: Introductionmentioning

confidence: 99%

Synthesis and in vitro reactivity of cis-dichloro-(pyridin-2-ylcarboxaldimine)platinum(II) complexes with DNA

Nikolcheva¹,

Vogels²,

Stefan³

et al. 2003

Can. J. Chem.

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Five platinum pyridin-2-ylcarboxaldimine complexes of the type cis-[PtCl 2 (2-C 5 H 4 NCH=NR)] (R = CH 2 CH 2 OH (1); R = N(CH 2 CH 2 ) 2 O (2); R = C 6 H 5 (3); R = 1-C 10 H 7 (4); R = (CH 2 ) 8 CH=CH(CH 2 ) 7 CH 3 (5)) were prepared and their in vitro reactivity towards a 20-base pair (single-and double-stranded) DNA determined using nuclease digest studies and RP-HPLC. Variation of the imine functionality allowed for the design of compounds with different physical and chemical properties. Complexes 1 and 3 showed binding to both single-and double-stranded DNA comparable to that of cisplatin (cis-[PtCl 2 (NH 3 ) 2 ]). Crystals of 1 were monoclinic, space group P2(1)/n, a = 9.6612 (15), b = 12.9678 (19), c = 9.7004(13) Å, β = 117.73(3)°, Z = 4. Résumé : On a préparé cinq complexes de pyridin-2-carboxaldimine et de platine du type cis-[PtCl 2 (2-C 5 H 4 NCH=NR)] (R = CH 2 CH 2 OH (1); R = N(CH 2 CH 2 ) 2 O (2); R = C 6 H 5 (3); R = 1-C 10 H 7 (4); R = (CH 2 ) 8 CH=CH(CH 2 ) 7 CH 3 (5)) et, faisant appel à des études de « RP-HPLC » et de digestion par une nucléase, on a évalué leur réactivité in vitro une molécule d'ADN à vingt paires de bases (à simple et à double brin). La variation de la fonction imine a permis de mettre au point des composés ayant des propriétés physiques et chimiques différentes. La fixation des complexes 1 et 3 à l'ADN à simple et à double brin semble être comparable à celle du cisplatine, cis-[PtCl 2 (NH 3 ) 2 ]. Les cristaux du composé 1 sont monocliniques, groupe d'espace P2(1)/n, avec a = 9,6612(15), b = 12,9678(19) et c = 9,7004(13) Å, β = 117,73(3)°et Z = 4.

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“…All complexes studied are of identical charge (+2) and differ by the L ligand only. There is no influence of the microenvironment in stabilizing either the H 2 O or the OH − ligand [6,29], and consequently the observed differences in pK a values of the aqua ligand essentially reflect the transmission of electronic effects from L via Pt to H 2 O. The expected qualitative trend, that a higher basicity of the pyridine ligand L lowers the acidity of the aqua ligand, is confirmed.…”

Section: Discussionmentioning

confidence: 99%

AquaGroupAcidity in Complexes of theType trans-[Pt(NH3 )2(L)(H2O)]2+ (with L = Substituted Pyridines). Linear, yetWeak Dependence of pKa of the Aqua Ligand from L Basicity

Galstyan

Shen

Lippert

2009

Zeitschrift Für Naturforschung B

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The pK a of the aqua ligand in complexes of the type trans-[Pt(NH 3 ) 2 (L)(H 2 O)] n+ depends on the nature of the ligand trans to H 2 O, as expected. With L = NH 3 or NH 2 R and n = 2, the pK a is around 6.0 -6.4. With L = N-heterocyclic ligands generally higher acidities of the aqua ligands are observed, with pK a values being in the range of 4.7 -5.4. These values are between those for L = H 2 O, n = 2 (4.4) and L = Cl − , n = 1 (5.7). For differently substituted pyridine ligands L a linear relationship exists between the pK a of the H 2 O ligand and the basicity of the heterocyclic ligand L, which is relatively weak, however.

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cis-[PtCl2(NH3){2-(2-hydroxyethyl)pyridine}] − an Analogue of the Anticancer Drug AMD473: Unusual Hydrolysis Rates and pKa Values for the Diaqua Adduct

Cited by 28 publications

References 17 publications

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

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

Synthesis and in vitro reactivity of cis-dichloro-(pyridin-2-ylcarboxaldimine)platinum(II) complexes with DNA

AquaGroupAcidity in Complexes of theType trans-[Pt(NH3 )2(L)(H2O)]2+ (with L = Substituted Pyridines). Linear, yetWeak Dependence of pKa of the Aqua Ligand from L Basicity

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cis-[PtCl2(NH3){2-(2-hydroxyethyl)pyridine}] − an Analogue of the Anticancer Drug AMD473: Unusual Hydrolysis Rates and pKa Values for the Diaqua Adduct

Cited by 28 publications

References 17 publications

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

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

Synthesis and in vitro reactivity of cis-dichloro-(pyridin-2-ylcarboxaldimine)platinum(II) complexes with DNA

AquaGroupAcidity in Complexes of theType trans-[Pt(NH3 )2(L)(H2O)]2+ (with L = Substituted Pyridines). Linear, yetWeak Dependence of pKa of the Aqua Ligand from L Basicity

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Product

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

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