Polynuclear palladium complexes with biogenic polyamines: AFM and voltammetric characterization

Abstract

Polynuclear Pd(II) complexes with biogenic polyamines present great potential clinical importance, due to their antiproliferative and cytotoxic activity coupled to less severe side-effects. The adsorption process and the redox behaviour of two polynuclear palladium chelates with spermine (Spm) and spermidine (Spd), Pd(II)-Spm and Pd(II)-Spd, as well as of their ligands Spm and Spd, were studied using atomic force microscopy (AFM) and voltammetry at highly oriented pyrolytic graphite and glassy carbon electrodes. AFM revealed different adsorption patterns and degree of surface coverage, correlated with the chelate structure, concentration of the solution, applied potential and voltammetric behaviour of the Spm, Spd, Pd(II)-Spm and Pd(II)-Spd systems. The voltammetric study of Spm and Spd showed that these biogenic polyamines undergo an irreversible and pH-dependent oxidation. In acid medium the polyamines are fully protonated, rendering their oxidation more difficult. With increasing pH the oxidation potential for both Spm and Spd is shifted to less positive values, indicating a greater ease of oxidation in alkaline medium. The Pd(II)-Spm and Pd(II)-Spd complexes dissociate at high negative or high positive potentials. The application of a positive potential induced the oxidation of these Pd complexes and the formation of mixed layers of palladium oxides, Spm/Spd and Pd(II)-Spm/Pd(II)-Spd.

Chemotherapeutic response to cisplatin-like drugs in human breast cancer cells probed by vibrational microspectroscopy

“…Following previous biological studies by the authors on the effect of the tested Pt(II) and Pd(II) spermine complexes on the growth and viability of several human cancer cells, [14][15][16]22,26,27,40,41,43,45 including the hormone-unresponsive breast carcinoma currently investigated, a cellular response at the biochemical level is presently sought, through analysis of the vibrational pattern of drug-treated and untreated cells. This multidisciplinary approach aims to link biological response to changes in cellular chemistry and metabolism, thus identifying the spectral markers of drug activity and paving the way for an understanding of the drug mode of action at the molecular level, hopefully helping to predict drug efficacy under specic conditions.…”

“…The data obtained within this work, coupled to conformational analysis of the metal complexes and cytological assays (for evaluation of growth-inhibition, cytotoxic and anti-metastatic activities) previously carried out at QFM-UC, [14][15][16]22,[25][26][27][40][41][42][43][44][45] will pave the way for future studies on other platinum and palladium-based polyamine agents prepared by the authors. This approach should provide valuable clues for the rational design of novel cisplatin-like drugs, displaying a higher efficiency, lower toxicity, decreased acquired resistance and possible oral administration.…”

“…glutathione) and pharmacodynamics, has been attained through vibrational spectroscopy (Raman, FTIR and Inelastic Neutron Scattering (INS)) [18][19][20][21][22][23][24] coupled to synchrotron-based Extended X-ray Absorption Fine Structure (EXAFS), 23 as well as by NMR metabolomics 22,25 and electrochemical techniques. 26,27 In order to design such effective chemotherapeutic agents, it is essential not only to determine their effect on cellular growth, metabolism and function, but also to understand the mechanisms (at a molecular level) associated with this biological impact. This can be accomplished through in vitro experiments in cells, followed by ex vivo and in vivo studies, coupled to high resolution spectroscopic techniques.…”

Anticancer drug impact on DNA – a study by neutron spectroscopy coupled with synchrotron-based FTIR and EXAFS

“…[4][5][6] Among these, polynuclear multifunctional Pt(II) and Pd(II) chelates with flexible biogenic polyamines as bridging ligands have been synthetized by the authors and evaluated as to their effect on several types of human neoplasias, namely the low prognosis, highly metastatic triple negative breast cancer against which a Pd(II) agent (Pd 2 Spm, Spm = spermine, H 2 N(CH 2 ) 3 NH(CH 2 ) 4 NH(CH 2 ) 3 NH 2 ) has yielded particularly promising results. 7 A number of studies have been conducted in the last few years on these Pt-and Pd-based complexes, reporting conformational profiles [8][9][10][11] and pharmacokinetic/pharmacodynamic behaviour, 12,13 and the effect on different human cancers 7,[14][15][16][17][18][19][20][21][22] including their impact on the cellular biochemical profile. [23][24][25] Unconventional pathways of cytotoxicity were disclosed, which are recognized to lead to an improved therapeutic efficiency coupled with a lower toxicity.…”

Anticancer Drug Impact on DNA – A Study by Neutron Spectrocopy, Synchrotron-based FTIR and EXAFS

“…(Kelland, 2007, Marques, 2013, Wheate, Walker et al, 2010 Among these, polynuclear multifunctional Pt(II) and Pd(II) chelates with flexible biogenic polyamines as bridging ligands have been synthetized by the authors and evaluated as to their effect on several types of human neoplasias, namely the low prognosis, highly metastatic triple negative breast cancer against which a Pd(II) agent (Pd 2 Spm, Spm=spermine, H 2 N(CH 2 ) 3 NH(CH 2 ) 4 NH(CH 2 ) 3 NH 2 ) has yielded particularly promising results. (Fiuza, Holy et al, 2011) A number of studies have been conducted in the last few years on these Pt-and Pd-based complexes, reporting conformational profiles (Batista de Carvalho, Parker et al, 2018, Fiuza, Amado et al, 2015, Marques, Valero et al, 2013 and pharmacokinetic/pharmacodynamic behaviour, (Corduneanu, Chiorcea-Paquim et al, 2010, Marques, Gianolio et al, 2015 and the effect on different human cancers(Batista de Carvalho, Medeiros et al, 2016a, Fiuza, Amado et al, 2006, Fiuza et al, 2011, Marques, Girao et al, 2002, Silva, Andersson et al, 2013, Silva, Fiuza et al, 2014, Soares, Fiuza et al, 2007, Tassoni, Bagni et al, 2010, Teixeira, Seabra et al, 2004, Tummala, Diegelman et al, 2010 including their impact on cellular biochemical profile. (Batista de Carvalho, Pilling et al, 2016b, Lamego, Marques et al, 2017, Marques, Batista de Carvalho et al, 2017 Unconventional pathways of cytotoxicity were disclosed, which are recognized to lead to an improved therapeutic efficiency coupled to a lower toxicity.…”