Chloro half-sandwich osmium(II) complexes: Influence of chelated N,N-ligands on hydrolysis, guanine binding, and cytotoxicity

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Chloro half-sandwich osmium(II) complexes: Influence of chelated N,N-ligands on hydrolysis, guanine binding, and cytotoxicity. / Peacock, Anna; Habtemariam, A; Moggach, SA; Prescimone, A; Parsons, S; Sadler, PJ.

In: Inorganic Chemistry, Vol. 46, No. 10, 14.05.2007, p. 4049-4059.

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Peacock, Anna ; Habtemariam, A ; Moggach, SA ; Prescimone, A ; Parsons, S ; Sadler, PJ. / Chloro half-sandwich osmium(II) complexes: Influence of chelated N,N-ligands on hydrolysis, guanine binding, and cytotoxicity. In: Inorganic Chemistry. 2007 ; Vol. 46, No. 10. pp. 4049-4059.

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@article{342087e5de574817a678cd4d46971bd3,
title = "Chloro half-sandwich osmium(II) complexes: Influence of chelated N,N-ligands on hydrolysis, guanine binding, and cytotoxicity",
abstract = "Relatively little is known about the kinetics or the pharmacological potential of organometallic complexes of osmium compared to its lighter congeners, iron and ruthenium. We report the synthesis of seven new complexes, [(eta(6)-arene)Os(NN)Cl](+), containing different bidentate nitrogen (N,N) chelators, and a dichlorido complex, [(eta(6)-arene)Os(N)Cl-2]. The X-ray crystal structures of seven complexes are reported: [(eta(6)-bip)Os(en)Cl]PF6 (1PF(6)), [(eta(6)-THA)Os(en)Cl]BF4 (2BF(4)), [(eta(6)-p-cym)Os(phen)Cl]PF6 (5PF(6)), [(eta(6)-bip)Os(dppz)Cl]PF6 (6PF(6)), [(eta(6)-bip)Os(azpy-NMe2)Cl]PF6 (7PF(6)), [(eta(6)-p-cym)Os(azpy-NMe2)Cl]PF6 (8PF(6)), and [(eta(6)-bip)Os(NCCH3-N)Cl-2] (9), where THA = tetrahydroanthracene, en = ethylenediamine, p-cym = p-cymene, phen = phenanthroline, bip = biphenyl, dppz = [3,2-a: 2',3'-c]phenazine and azpy-NMe2 = 4-(2-pyridylazo)-N,N-dimethylaniline. The chelating ligand was found to play a crucial role in enhancing aqueous stability. The rates of hydrolysis at acidic pH* decreased when the primary amine N-donors (NN = en, t(1/2) = 0.6 h at 318 K) are replaced with pi-accepting pyridine groups (e.g., NN = phen, t(1/2) = 9.5 h at 318 K). The Os-II complexes hydrolyze up to 100 times more slowly than their Ru-II analogues. The pK*(a) of the aqua adducts decreased with a similar trend (pK*(a) = 6.3 and 5.8 for en and phen adducts, respectively). [(eta(6)-bip)Os(en)Cl]PF6/BF4 (1PF(6)/BF4) and [(eta(6)-THA)Os(en)Cl]BF4 (2BF(4)) were cytotoxic toward both the human A549 lung and A2780 ovarian cancer cell lines, with IC50 values of 6-10 mu M, comparable to the anticancer drug carboplatin. 1BF(4) binds to both the N7 and phosphate of 5'-GMP (ratio of 2:1). The formation constant for the 9-ethylguanine (9EtG) adduct [(eta(6)-bip)M(en)(9EtG)](2+) was lower for Os-II (log K = 3.13) than Ru-II (log K = 4.78), although the Os-II adduct showed some kinetic stability. DNA intercalation of the dppz ligand in 6PF(6) may play a role in its cytotoxicity. This work demonstrates that the nature of the chelating ligand can play a crucial role in tuning the chemical and biological properties of [(eta(6)-arene)Os(NN)Cl](+) complexes.",
author = "Anna Peacock and A Habtemariam and SA Moggach and A Prescimone and S Parsons and PJ Sadler",
year = "2007",
month = may
day = "14",
doi = "10.1021/ic062350d",
language = "English",
volume = "46",
pages = "4049--4059",
journal = "Inorganic Chemistry",
issn = "0020-1669",
publisher = "American Chemical Society",
number = "10",

}

RIS

TY - JOUR

T1 - Chloro half-sandwich osmium(II) complexes: Influence of chelated N,N-ligands on hydrolysis, guanine binding, and cytotoxicity

AU - Peacock, Anna

AU - Habtemariam, A

AU - Moggach, SA

AU - Prescimone, A

AU - Parsons, S

AU - Sadler, PJ

PY - 2007/5/14

Y1 - 2007/5/14

N2 - Relatively little is known about the kinetics or the pharmacological potential of organometallic complexes of osmium compared to its lighter congeners, iron and ruthenium. We report the synthesis of seven new complexes, [(eta(6)-arene)Os(NN)Cl](+), containing different bidentate nitrogen (N,N) chelators, and a dichlorido complex, [(eta(6)-arene)Os(N)Cl-2]. The X-ray crystal structures of seven complexes are reported: [(eta(6)-bip)Os(en)Cl]PF6 (1PF(6)), [(eta(6)-THA)Os(en)Cl]BF4 (2BF(4)), [(eta(6)-p-cym)Os(phen)Cl]PF6 (5PF(6)), [(eta(6)-bip)Os(dppz)Cl]PF6 (6PF(6)), [(eta(6)-bip)Os(azpy-NMe2)Cl]PF6 (7PF(6)), [(eta(6)-p-cym)Os(azpy-NMe2)Cl]PF6 (8PF(6)), and [(eta(6)-bip)Os(NCCH3-N)Cl-2] (9), where THA = tetrahydroanthracene, en = ethylenediamine, p-cym = p-cymene, phen = phenanthroline, bip = biphenyl, dppz = [3,2-a: 2',3'-c]phenazine and azpy-NMe2 = 4-(2-pyridylazo)-N,N-dimethylaniline. The chelating ligand was found to play a crucial role in enhancing aqueous stability. The rates of hydrolysis at acidic pH* decreased when the primary amine N-donors (NN = en, t(1/2) = 0.6 h at 318 K) are replaced with pi-accepting pyridine groups (e.g., NN = phen, t(1/2) = 9.5 h at 318 K). The Os-II complexes hydrolyze up to 100 times more slowly than their Ru-II analogues. The pK*(a) of the aqua adducts decreased with a similar trend (pK*(a) = 6.3 and 5.8 for en and phen adducts, respectively). [(eta(6)-bip)Os(en)Cl]PF6/BF4 (1PF(6)/BF4) and [(eta(6)-THA)Os(en)Cl]BF4 (2BF(4)) were cytotoxic toward both the human A549 lung and A2780 ovarian cancer cell lines, with IC50 values of 6-10 mu M, comparable to the anticancer drug carboplatin. 1BF(4) binds to both the N7 and phosphate of 5'-GMP (ratio of 2:1). The formation constant for the 9-ethylguanine (9EtG) adduct [(eta(6)-bip)M(en)(9EtG)](2+) was lower for Os-II (log K = 3.13) than Ru-II (log K = 4.78), although the Os-II adduct showed some kinetic stability. DNA intercalation of the dppz ligand in 6PF(6) may play a role in its cytotoxicity. This work demonstrates that the nature of the chelating ligand can play a crucial role in tuning the chemical and biological properties of [(eta(6)-arene)Os(NN)Cl](+) complexes.

AB - Relatively little is known about the kinetics or the pharmacological potential of organometallic complexes of osmium compared to its lighter congeners, iron and ruthenium. We report the synthesis of seven new complexes, [(eta(6)-arene)Os(NN)Cl](+), containing different bidentate nitrogen (N,N) chelators, and a dichlorido complex, [(eta(6)-arene)Os(N)Cl-2]. The X-ray crystal structures of seven complexes are reported: [(eta(6)-bip)Os(en)Cl]PF6 (1PF(6)), [(eta(6)-THA)Os(en)Cl]BF4 (2BF(4)), [(eta(6)-p-cym)Os(phen)Cl]PF6 (5PF(6)), [(eta(6)-bip)Os(dppz)Cl]PF6 (6PF(6)), [(eta(6)-bip)Os(azpy-NMe2)Cl]PF6 (7PF(6)), [(eta(6)-p-cym)Os(azpy-NMe2)Cl]PF6 (8PF(6)), and [(eta(6)-bip)Os(NCCH3-N)Cl-2] (9), where THA = tetrahydroanthracene, en = ethylenediamine, p-cym = p-cymene, phen = phenanthroline, bip = biphenyl, dppz = [3,2-a: 2',3'-c]phenazine and azpy-NMe2 = 4-(2-pyridylazo)-N,N-dimethylaniline. The chelating ligand was found to play a crucial role in enhancing aqueous stability. The rates of hydrolysis at acidic pH* decreased when the primary amine N-donors (NN = en, t(1/2) = 0.6 h at 318 K) are replaced with pi-accepting pyridine groups (e.g., NN = phen, t(1/2) = 9.5 h at 318 K). The Os-II complexes hydrolyze up to 100 times more slowly than their Ru-II analogues. The pK*(a) of the aqua adducts decreased with a similar trend (pK*(a) = 6.3 and 5.8 for en and phen adducts, respectively). [(eta(6)-bip)Os(en)Cl]PF6/BF4 (1PF(6)/BF4) and [(eta(6)-THA)Os(en)Cl]BF4 (2BF(4)) were cytotoxic toward both the human A549 lung and A2780 ovarian cancer cell lines, with IC50 values of 6-10 mu M, comparable to the anticancer drug carboplatin. 1BF(4) binds to both the N7 and phosphate of 5'-GMP (ratio of 2:1). The formation constant for the 9-ethylguanine (9EtG) adduct [(eta(6)-bip)M(en)(9EtG)](2+) was lower for Os-II (log K = 3.13) than Ru-II (log K = 4.78), although the Os-II adduct showed some kinetic stability. DNA intercalation of the dppz ligand in 6PF(6) may play a role in its cytotoxicity. This work demonstrates that the nature of the chelating ligand can play a crucial role in tuning the chemical and biological properties of [(eta(6)-arene)Os(NN)Cl](+) complexes.

U2 - 10.1021/ic062350d

DO - 10.1021/ic062350d

M3 - Article

C2 - 17441712

VL - 46

SP - 4049

EP - 4059

JO - Inorganic Chemistry

JF - Inorganic Chemistry

SN - 0020-1669

IS - 10

ER -