Thermodynamics of sorption of platinum on superparamagnetic nanoparticles functionalized with mercapto groups

The adsorption of Pt(IV) by iron oxide (Fe₃O₄) superparamagnetic nanoparticles (SPION) functionalized with 3-mercaptopropionic acid (3-MPA) is investigated by means of inductively coupled plasma optical emission spectrometry and isothermal titration calorimetry. Experimental ICP data are better fitted by Langmuir rather than Freundlich isotherms. The whole thermodynamic parameters and maximum loading capacity for the adsorption process of Pt(IV) on the functionalized SPION nanoparticles (SPION@3-MPA) are obtained. The process is enthalpy-driven, while entropy is largely unfavourable suggesting that some other interaction should be present in addition to the electrostatic ones with the coverage surface. When compared to other thiol-functionalized materials, the SPION@3-MPA can be considered an interesting adsorbent for Pt(IV), especially with respect to the short contact time evidenced

Using Theory to Reinterpret the Kinetics of Monofunctional Platinum Anticancer Drugs: Stacking Matters

The monofunctional platinum drug phenanthriplatin (phenPt) blocks the replication of cancer cells even if it reacts with only one guanine base. However, there is still insufficient experimental data to improve its cytotoxicity and all previously proposed chemical modifications of the parent structure have resulted in a loss of activity. We use theoretical tools to illustrate the key steps in the biological mechanisms of phenPt; that is, its activation in water and the subsequent attack on DNA. Our simulations suggest that the measured kinetic parameters, which are based on free nucleobases in solution, need to be reinterpreted because the self-assembled stacked reactive adduct formed in the reaction is inaccessible in real DNA. The constants reported here will help guide future work in the synthesis of anticancer platinum drugs

Eu(iii) and Tb(iii) complexes of 6-fold coordinating ligands showing high affinity for the hydrogen carbonate ion: A spectroscopic and thermodynamic study

In the present contribution, four classes of Ln(iii) complexes (Ln = Eu and Tb) have been synthesized and characterized in aqueous solution. They differ by charge, Ln(bpcd)+ [bpcd2- = N,N'-bis(2-pyridylmethyl)-trans-1,2-diaminocyclohexane N,N'-diacetate] and Ln(bQcd)+ (bQcd2- = N,N'-bis(2-quinolinmethyl)-trans-1,2-diaminocyclohexane N,N'-diacetate) being positively charged and Ln(PyC3A) (PyC3A3- = N-picolyl-N,N',N'-trans-l,2-cyclohexylenediaminetriacetate) and Ln(QC3A) (QC3A3- = N-quinolyl-N,N',N'-trans-l,2-cyclohexylenediaminetriacetate) being neutral. Combined DFT, spectrophotometric and potentiometric studies reveal the presence, under physiological conditions (pH 7.4), of a couple of equally and highly stable isomers differing by the stereochemistry of the ligands (trans-N,N and trans-O,O for bpcd2- and bQcd2-; trans-O,O and trans-N,O for PyC3A3- and QC3A3-). Their high log\u2009\u3b2 values (9.97 < log\u2009\u3b2 < 15.68), the presence of an efficient antenna effect and the strong increase of the Ln(iii) luminescence intensity as a function of the hydrogen carbonate concentration in physiological solution, render these complexes as very promising optical probes for a selective detection of HCO3-in cellulo or in extracellular fluid. This particularly applies to the cationic Eu(bpcd)+, Tb(bpcd)+ and Eu(bQcd)+ complexes, which are capable of guesting up to two hydrogen carbonate anions in the inner coordination sphere of the metal ion, so that they show an unprecedented affinity towards HCO3- (log\u2009K for the formation of the adduct in the 4.6-5.9 range)

Effect of the Heteroaromatic Antenna on the Binding of Chiral Eu(III) Complexes to Bovine Serum Albumin

The cationic enantiopure R) and luminescent Eu(III) complex [Eu(bisoQcd)(H2O)(2)] OTf (with bisoQcd = N,N'-bis(2-isaquinolinmethyl)-trarts-1,2diaminocyclohexane N/N1 -diacetate and OTf = triflate) was synthesized and characterized. At physiological pH, the 1:1 [Eu(bisoQcd)(H2O)(2)](+) species, possessing two water molecules in the inner coordination sphere, is largely dominant. The interaction with bovine serum albumin (BSA) was studied by means of several experimental techniques, such as luminescence spectroscopy, isothermal titration calorimeti-y (ITC), molecular docking (MD), and molecular dynamics simulations M11.-.)S). In this direction, a ligand competition study was also performed by using three clinically established drugs (i.e., ibuprofen, warfarin, and digito)cin). The nature of this interaction is strongly affected by the type of the involved heteroaromatic antenna in the complexes. In fact, the presence of isoqiiinolirie rings drives the corresponding complex toward the protein superficial area containing the tryptophan residue 134 (Trp134). As the main consequence, the metal center undergoes the loss of one water molecule upon interaction with the side chain of a glutamic acid residue. On the other hand, the similar complex containing pyridine rings f[Eti(bpcd)(H2O)(2)]Cl with bpcd = N,N'-bis(2-pytidylmethyl)-trans-1,2-diaminocyclohexane N,N'-diacetate)interacts more weakly with the protein in a different superficial cavity, without losing the coordinated water molecules

Cu(i) and Ag(i) complex formation with the hydrophilic phosphine 1,3,5-triaza-7-phosphadamantane in different ionic media. How to estimate the effect of a complexing medium

The complexes of Cu(i) and Ag(i) with 1,3,5-triaza-7-phosphadamantane (PTA) are currently studied for their potential clinical use as anticancer agents, given the cytotoxicity they exhibited in vitro towards a panel of several human tumor cell lines. These metallodrugs are prepared in the form of [M(PTA)4]+ (M = Cu+, Ag+) compounds and dissolved in physiological solution for their administration. However, the nature of the species involved in the cytotoxic activity of the compounds is often unknown. In the present work, the thermodynamics of formation of the complexes of Cu(i) and Ag(i) with PTA in aqueous solution is investigated by means of potentiometric, spectrophotometric and microcalorimetric methods. The results show that both metal(i) ions form up to four successive complexes with PTA. The formation of Ag(i) complexes is studied at 298.15 K in 0.1 M NaNO3 whereas the formation of the Cu(i) one is studied in 1 M NaCl, where Cu(i) is stabilized by the formation of three successive chloro-complexes. Therefore, for this latter system, conditional stability constants and thermodynamic data are obtained. To estimate the affinity of Cu(i) for PTA in the absence of chloride, Density Functional Theory (DFT) calculations have been done to obtain the stoichiometry and the relative stability of the possible Cu/PTA/Cl species. Results indicate that one chloride ion is involved in the formation of the first two complexes of Cu(i) ([CuCl(PTA)] and [CuCl(PTA)2]) whereas it is absent in the successive ones ([Cu(PTA)3]+ and [Cu(PTA)4]+). The combination of DFT results and thermodynamic experimental data has been used to estimate the stability constants of the four [Cu(PTA)n]+ (n = 1-4) complexes in an ideal non-complexing medium. The calculated stability constants are higher than the corresponding conditional values and show that PTA prefers Cu(i) to the Ag(i) ion. The approach used here to estimate the hidden role of chloride on the conditional stability constants of Cu(i) complexes may be applied to any Cu(i)/ligand system, provided that the stoichiometry of the species in NaCl solution is known. The speciation for the two systems shows that the [M(PTA)4]+ (M = Cu+, Ag+) complexes present in the metallodrugs are dissociated into lower stoichiometry species when diluted to the micromolar concentration range, typical of the in vitro biological testing. Accordingly, [Cu(PTA)2]+, [Cu(PTA)3]+ and [Ag(PTA)2]+ are predicted to be the species actually involved in the cytotoxic activity of these compounds. \ua9 2017 The Royal Society of Chemistry

A chiral lactate reporter based on total and circularly polarized Tb(iii) luminescence

The coordination features and signaling of a l-lactate ion by a [Tb(bpcd)]+(bpcd = N,N′-bis(2-pyridylmethyl)-trans-1,2-diaminocyclohexane-N,N′-diacetate) complex have been investigated by means of a combination of techniques, including total luminescence, calorimetry and circularly polarized luminescence. The l-lactate/[Tb(bpcd)]+association constant, determined by both luminescence titration and isothermal titration calorimetry, indicates a weak interaction (log K = 1.3-1.45) between the analyte and both enantiomers of the complex. The theoretical DFT calculations suggest that the most likely coordination of l-lactate to the possible stereoisomers of the [Tb(S,S-bpcd)]+complex (trans-O,O or trans-Npy,Npy) is one involving a hydroxyl group. The results of [Tb(rac-bpcd)]+as a chiroptical luminescent probe of l-lactate underline the peculiar role of the chiral 1,2-diaminocyclohexane (DACH) backbone. Indeed, the target anion is capable of inducing CPL activity in the racemic mixture of Tb complexes containing DACH-based ligands. The same is not observed for the achiral analogue [Tb(bped)]+(bped = N,N′-bis(2-pyridylmethyl)ethylenediamine-N,N′-diacetate) complex, likely because of the flexibility of the ethylenic group which allows an interconversion between different isomers which produces a null net CPL activity. Thanks to the differential quantum yield of the two diastereomeric species (R,R)-l and (S,S)-l, one can use the racemic complex to reveal l-lactate by measuring the induced CPL spectrum. Interestingly, this has been demonstrated in a commercial complex solution for medical use, containing several electrolytes, namely Ringer's lactate