RT Journal Article
T1 Diruthenium complexes as pH-responsive delivery systems: a quantitative assessment
A1 Coloma Manjón-Cabeza, Isabel
A1 Cortijo Montes, Miguel
A1 Mancheño Real, María José
A1 León González, María Eugenia De
A1 Gutierrez, Crisanto
A1 Desvoyes, Bénédicte
A1 Herrero Domínguez, Santiago
A2 ROYAL SOCIETY OF CHEMISTRY, 
AB The controlled release of biologically active species from diruthenium compounds is crucial for the development of selective drug delivery systems based on such complexes, which in addition display antineoplastic properties by themselves. In the present work, we analyse in detail the kinetics of the pH-triggered release of the auxin-related hormones 2,4-D (2,4-dichlorophenoxyacetate) and NAA (1-naphthaleneacetate) from the metal–metal bonded tris(formamidinato) Ru25+ complexes [Ru2Cl(μ-DPhF)3(μ-2,4-D)](Ru2,4-D), [Ru2Cl(μ-DPhF)3(μ-NAA)] (RuNAA), [Ru2Cl(μ-DAniF)3(μ-2,4-D)] (Ru’2,4-D) and [Ru2Cl(μ-DAniF)3(μ-NAA)] (Ru’NAA) (DPhF = N,N’-diphenylformamidinate, DAniF = N,N’-bis(p-methoxy)phenylformamidinate).Moreover, the synthesis and complete characterisation of [Ru2Cl(μ-DAniF)3(μ-IAA)] (Ru’IAA, IAA = indole-3-acetate), Ru’2,4-D and Ru’NAA, including the crystal structure of the two latter ones, is reported. The release of auxins is studied through a fluorimetric quantitative assay, which allows determining the influence of different formamidinate ancillary ligands and the nature of the outgoing auxin ligand in the release process. Chemometrics is employed to evaluate the statistical significance of the variables. The release of auxins is slower at physiological pH and occurs faster at slightly acidic pH values.Compounds containing DPhF ancillary ligands and NAA outgoing ligand present a slower dissociation of the auxin, which is not complete in the first 24 h. The release rate is also correlated with the bond distance O1(auxin)–Ru1(hexacoordinated). A mechanism of the substitution reaction is tentatively proposed based on these findings. Overall, these results pave the way towards new systems for the controlled delivery of antineoplastic drugs under mild-acidic conditions like those surrounding solid tumours.
PB Royal Society of Chemistry
SN 2052-1553
YR 2023
FD 2023
LK https://hdl.handle.net/20.500.14352/92750
UL https://hdl.handle.net/20.500.14352/92750
LA eng
NO Coloma, I; Cortijo, M; Mancheño, MJ; León-González, ME; Gutierrez, C; Desvoyes, B; Herrero, S, Diruthenium complexes as pH-responsive delivery systems: a quantitative assessment. 2023, 10(15):4402
NO Comunidad de Madrid
NO Ministerio de Ciencia e Innovación (España)
NO Universidad Complutense de Madrid
DS Docta Complutense
RD 24 jul 2024