Nucleophile Concentration Research Articles

Kinetic and mechanistic investigation into the influence of substituents on the substitution reactions of Pt(II) NCN-donor complexes

The substitution kinetics of cyclometallated platinum(II) complexes [PtL1Cl] (L1 = 1,3-di(2-pyridyl)benzene), [PtL2Cl] (L2 = 3,5-di(2-pyridinyl)-fluorobenzene), [PtL3Cl] (L3 = 2,4-di(2-pyridinyl)-fluorobenzene) and [PtL4Cl] (L4 = 3,5-di(2-pyridinyl)-toluene) with neutral nitrogen-donor nucleophiles imidazole, 1-methylimidazole, 1,2-dimethylimidazole, pyrazole and 1,2,4-triazole were investigated under pseudo-first-order conditions in methanol solution with an ionic strength of 0.1 M. The rate of substitution of the chloride ligand was studied as a function of nucleophile concentration and temperature using stopped-flow spectrophotometric techniques. The observed pseudo-first-order rate constants, kobs, for the substitution reactions obeyed the rate law kobs = k2[Nu]. The reactivity of these complexes follows the order PtL2Cl > PtL3Cl > PtL4Cl > PtL1Cl. The lability of the chloride ligand is influenced by the extent of π-backbonding and also by the σ-trans effect. The reactivity of the nucleophiles depends on their basicity, inductive effect and steric hindrance. Second-order kinetics and negative activation entropies support an associative substitution mechanism. The experimental data are supported by the results of DFT calculations.

Flow‐Based Enzymatic Ligation by Sortase A

Sortase-mediated ligation (sortagging) is a versatile, powerful strategy for protein modification. Because the sortase reaction reaches equilibrium, a large excess of polyglycine nucleophile is often employed to drive the reaction forward and suppress sortase-mediated side reactions. A flow-based sortagging platform employing immobilized sortase A within a microreactor was developed that permits efficient sortagging at low nucleophile concentrations. The platform was tested with several reaction partners and used to generate a protein bioconjugate inaccessible by solution-phase batch sortagging.

The role of diaminocyclohexane and diaminobenzene linking bridges on the aqua substitution of chelated dinuclear Pt(II) complexes by nitrogen donor heterocycles. A kinetic and mechanistic study

The substitution of the aqua ligands from six Pt(II) complexes, viz., [Pt(H2O)(N,N-bis(2-pyridylmethyl)cyclohexylamine](ClO4)2 (Pt1); [{Pt(H2O)}2(N,N,N′,N′-tetrakis(2-pyridylmethyl)-trans-1,4-cyclohexyldiamine)](ClO4)4 (Pt2); [{Pt(H2O)}2(N,N,N′,N′-tetrakis(2-pyridylmethyl)-4,4′-methylenedicyclohexyldiamine)](ClO4)4 (Pt3); [Pt(H2O)N,N-bis(2-pyridylmethyl)phenylamine)](ClO4)2 (Pt4); [{Pt(H2O)}2(N,N,N′,N′-tetrakis(2-pyridylmethyl)-1,4-phenyldiamine](ClO4)4 (Pt5); and [{Pt(H2O)}2(N,N,N′,N′-tetrakis(2-pyridylmethyl)-4,4′-methylenediphenyldiamine)](ClO4)4 (Pt6), by nitrogen heterocyclic ligands{viz., pyrazole (Pz); 3-methylpyrazole (mPz); 1,2,4-triazole (Tz) and pyrazine (Pzn)} were studied in an aqueous 0.01 M perchloric acid medium. The substitutions were investigated under pseudo-first-order conditions as a function of the concentration of nucleophiles and reaction temperature using UV–visible spectrophotometry. The substitution of the aqua ligands by all the nitrogen donor heterocycles proceeded via a single step whose rate decreased in the respective orders: Pt1 > Pt3 > Pt2 and Pt4 > Pt6 > Pt5 in the two sets of complexes. Of the nucleophiles used in this study, pyrazine was the most reactive and the complete order of the rate of aqua substitution was Pzn >> Pz > Tz > mPz. The large and negative activation entropies and low but positive enthalpies of activation values support a significant contribution from bond making in the transition state of the substitution process.

Electrochemical Oxidation of Catechols in the Presence of Triethyl Phosphite

The mechanism of electrochemical oxidation of catechol and some of its derivatives have been studied in the presence of triethyl phosphite as a nucleophile in aqueous solution. Voltammetric studies indicate that the quinones derived from catechol, and its derivatives, participate in Michael addition reaction with triethyl phosphite. The reaction mechanism consists of electron transfer followed by a chemical reaction which is named as an EC mechanism. The homogeneous rate constants (kobs) were estimated by comparing the experimental cyclic voltammograms with the digitally simulated voltammograms based on EC mechanism. Also the effects of nucleophile concentration and substituted group of catechols on voltammetric behavior and the rate constants of chemical reactions were examined.

Para-hormesis: An innovative mechanism for the health protection brought by antioxidants in wine

We have recently proposed a new paradigm for understanding how antioxidants in fruit and vegetables provide protective effects for health (1). Here we describe how this new paradigm is relevant to explaining how polyphenols in wine can provide health benefits. The new paradigm of para-hormesis is based on the reality that in cells, the by far major mechanism is enzyme-catalyzed reduction of hydroperoxides rather than non-enzymatic scavenging of free radicals and other oxidants and that dietary antioxidants increase enzymes and their substrates. Indeed, non-enzymatic scavenging by wine polyphenols may be restricted to the intestinal lumen as kinetic considerations rule out a significant contribution of non-enzymatic scavenging in cells. Indeed, antioxidants function through their metabolism in cells to electrophiles that induce enzymes and elevate the concentrations of nucleophiles, particular NADPH, glutathione and thioredoxin that are the substrates for these enzymes. This maintenance of nucleophilic tone provides the means for antioxidant defense

OP01 Visible and chemiluminescent methods for H2S detection and quantification

Hydrogen sulfide is an important biological signalling molecule and an important target for environmental detection. A major challenge in developing small-molecule, reaction-based probes for H2S detection and quantification is overcoming the much higher concentration of biological nucleophiles, such as reduced glutathione (GSH). In this presentation, we present two new H2S detection and quantification methods, both of which can be used to measure H2S analytically using common laboratory equipment or, alternatively, can be used for qualitative naked-eye H2S detection. Colorimetric H2S detection and quantification: The developed method utilizes a new strategy for reaction-based H2S detection facilitated by nucleophilic aromatic substitution of H2S onto an electrophilic nitrobenzofurazan (NBD) chromophore. The resultant platform reacts quickly with H2S (

Bridge‐Splitting Reactions of Platinum(II) Complexes with Parametalated Pyridine Spacer Groups: A Kinetic and Mechanistic Study

ABSTRACTSubstitution reactions of three dinuclear Pt(II) complexes connected by a pyridine‐bridging ligand of variable length, namely [ cis‐{PtOH2(NH3)2}2–μ–L]4+, where L = 4,4′‐bis(pyridine)sulfide (Pt1), 4,4′‐bis(pyridine)disulfide (Pt2), and 1,2‐bis(4‐pyridyl)ethane (Pt3) with S‐donor nucleophiles (thiourea, 1,3‐dimethyl‐2‐thiourea, and 1,1,3,3‐tetramethyl‐2‐thiourea) and anionic nucleophiles (SCN−, I−, and Br−) were investigated. The substitutions were followed under pseudo–first‐order conditions as a function of the nucleophile concentration and temperature, using stopped‐flow and UV–visible spectrophotometric methods. The observed pKavalues were, respectively,Pt1(pKa1: 4.86; pKa2: 5.53),Pt2(pKa1: 5.19; pKa2: 6.42), andPt3(pKa1: 5.04; pKa2: 5.45). The second‐order rate constants for the lability of aqua ligands in the first step decreased in the orderPt2>Pt3>Pt1, whereas for the second step it isPt1>Pt2>Pt3. The obtained results indicate that introduction of a spacer atom(s) on the structure of the bridging ligand influences the substitution reactivity as well as acidity of the investigated dinuclear Pt(II) complexes. Also nonplanarity of the bridging ligand ofPt1complex significantly slows down the rate of substitution due to steric hindrance, whereas release of the strain enhances the dissociation of the bridging ligand. The release of the bridging ligand in the second step was confirmed by the1H NMR ofPt1‐Clwith thiourea in DMF‐d7. The temperature dependence of the second–order rate constants and the negative values of entropies of activation (ΔS#) support an associative mode of the substitution mechanism.

Substituent effects on the formation and nucleophile selectivity of ring‐substituted phenonium ions in aqueous solution

The reaction of 2-(4-methyphenyl)ethyl tosylate (Me-1-OTs) in 50/50 (v/v) trifluoroethanol/water at 25 °C is first-order in the concentration of azide anion nucleophile. A carbon-13 NMR analysis of the products of the reactions of Me-1-[α-13C]OTs in 50/50 (v/v) trifluoroethanol/water at 25 °C shows the formation of Me-1-[β-13C]OH, Me-1-[β-13C]OCH2CF3 and Me-1-[β-13C]N3 from the trapping of a symmetrical 4-methylphenonium ion reaction intermediate Me-2+. The formation of Me-1-[α-13C]N3 by concerted bimolecular displacement of azide ion at Me-1-[α-13C]OTs (kN = 3.8 × 10-6 M-1 s-1) and of Me-1-[α-13C]OH and Me-1-[α-13C]OCH2CF3 by concerted bimolecular displacement of solvent (ksolv = 1.8 × 10-8 s-1) is also observed. An analysis of the rate and product data provides a value of kaz/ks = 32 M-1 for partitioning of Me-2+ between addition of azide ion and solvent that is nearly 3-fold smaller than kaz/ks = 83 M-1 reported in an earlier study on the partitioning of MeO-2+ [J. Org. Chem.2011, 76, 9568]. This change is attributed to a decrease in nucleophile selectivity with increasing electrophile reactivity for the activation-limited addition of solvent and azide anion to X-2+. These data set a limit of 1/ks ≥ 10-7 s for the lifetime of Me-2+ in aqueous solution.

Kinetics of chloride substitution in [Pt(bpma)Cl]+ and [Pt(gly-met-S,N,N)Cl] complexes by thiourea, nitrites, and iodides

AbstractSubstitution of chloride in [PtCl(bpma)]+ and [PtCl(gly-met-S,N,N)], where bpma is bis(2-pyridylmethyl)amine and gly-met-S,N,N is glycyl-l-methionine, was studied as a function of the entering nucleophile concentration and temperature. Reactions between the platinum(II) complexes and thiourea (TU), iodides (I−), and nitrites(III) (NO2−) were carried out in aqueous solutions using conventional UV-VIS spectrophotometry. Suitable ionic conditions were reached by an addition of 0.1 M NaClO4 and 0.01 M NaCl (to suppress hydrolysis). The second-order rate constants, k 2, for the studied reactions with NO2− varied between 0.036–0.038 M−1 s−1, and for the reactions with TU between 0.095–1.06 M−1 s−1, respectively. The reaction between TU and the [PtCl(bpma)]+ ion is ten times faster than that of the [PtCl(gly-met-S,N,N)] complex. An analysis of the activation parameters, ΔH ≠ and ΔS ≠, for the selected reactions clearly shows their associative nature.

Complex formation reactions of two sterically hindered platinum(II) complexes with some N-bonding ligands

The kinetics of the complex formation reactions of two [(TLtBu)PtCl]+ and [Pt(tpdm)Cl]+ complexes (TLtBu = 2,6-bis[(1,3-di-tert-butylimidazolin-2-imino)methyl]pyridine and tpdm = terpyridinedimethane) with N-donor ligands, l-histidine (L-His), inosine (Ino), inosine-5′-monophosphate (5′-IMP) and guanosine-5′-monophosphate (5′-GMP), were studied. All reactions were studied under pseudo-first-order conditions as a function of nucleophile concentration and temperature in aqueous 0.1 M NaClO4 solution in the presence of 10 mM NaCl using variable-temperature Uv–Vis spectrophotometry. The order of reactivity of the studied ligands is L-His > Ino > 5′-GMP > 5′-IMP. This order of reactivity is in relation to their electronic properties and structures. The mechanism of the substitution reactions is associative in nature as supported by the negative entropy of activation.

Substitution reactions in dinuclear platinum(II) complexes: an evaluation of the influence of the diazine-bridging ligand on reactivity

A kinetic study of aqua substitution in dinuclear Pt(II) complexes, [{cis-Pt(OH2)(NH3)2}2-μ-pmn](ClO4)2 (pmn), [{cis-Pt(OH2)(NH3)2}2-μ-pdn](ClO4)2 (pdn), [{cis-Pt(OH2)(NH3)2}2-μ-qzn](ClO4)2 (qzn), [{cis-Pt(OH2)(NH3)2}2-μ-pht](ClO4)2 (pht) and [{cis-Pt(OH2)(NH3)2}2-μ-pzn](ClO4)2 (pzn) (pmn = pyrimidine, pdn = pyridazine, qzn = quinazoline, pht = phthalazine, pzn = pyrazine) by different sulphur-donor nucleophiles, thiourea (TU), N,N–dimethylthiourea (DMTU) and N,N,N,N–tetramethylthiourea (TMTU) was carried out. The reactions were followed under pseudo-first-order conditions as a function of nucleophile concentration and temperature using stopped-flow and UV–Vis spectrophotometric methods. The reactivity of the nucleophiles follows the order TU > DMTU > TMTU. The general order of reactivity for the aqua complexes follows pzn > qzn > pmn > pdn > pht which is confirmed by the obtained pK a values and the quantum chemical calculated NBO charges at the metal centre. The negative values reported for the activation entropy confirm the associative nature of the substitution process. The results demonstrate the strong connection between structural and electronic characteristics of the diazine-bridging ligand and reactivity of the dinuclear Pt(II) complexes. The substitution behaviour of the cis-[{Pt(NH3)2H2O}2-µ-(NN)]4+ complexes is presented, and the trend in reactivity towards S-donor nucleophiles is significantly influenced by the relative disposition of the two Pt(II) centres and, in part, to π-resonance effect of diazine-bridging ligand.

Kinetics and mechanism for the substitution reactions of monoaquamonochloro-(piperazine) palladium (II) complex with L-methionine and thiourea in aqueous solution

The interaction of the palladium(II) complex [Pd(Pip)Cl(H2O)] + , where Pip is piperazine, with the sulphur donor nucleophiles; L-methionine (L-Met), and thiourea (tu) was studied under pseudo-first-order conditions as a function of nucleophile concentration and temperature, using UV-Visible spectrophotometric and stopped-flow techniques. Two consecutive reaction steps were observed for the substitution process with L-methionine. For the substitution with thiourea, a third reaction step, the displacement of the labilized amine, as a result of the strong trans-effect of thiourea ligand was observed. 1HNMR spectroscopy was used to follow the substitution of the ligand by thiourea. The activation parameters for all reactions studied suggest an associative substitution mechanism. The interaction of the monoaquamonochloro-(piperazine) Palladium (II) complex [Pd(Pip)Cl(H2O)] + , where Pip is piperazine, with the sulphur donor nucleophiles; L-methionine (L-Met), and thiourea (tu) was studied under pseudo-first-order conditions as a function of nucleophile concentration and temperature, using UV-Visible spectrophotometric and stopped-flow techniques. Two consecutive reaction steps were observed for the substitution process with L- methionine. For the substitution with thiourea, three reaction steps were observed.

Structural and catalytic aspects of copper(II) complexes containing 2,6-bis(imino)pyridyl ligands

The synthesis, structure, and ligand substitution mechanism of a new five-coordinate trigonal-bipyramidal copper(II) complex, [CuII(py tBuMe2N3)Cl2] (1), with a sterically constrained py tBuMe2N3 chelate ligand, py tBuMe2N3 = 2,6-bis-(ketimino)pyridyl, are reported. The kinetics and mechanism of chloride substitution by thiourea, as a function of nucleophile concentration, temperature, and pressure, were studied in detail and compared with an earlier study reported for the analogous complex [CuII(py tBuN3)Cl2] (2) [py tBuN3 = 2,6-bis-(aldimino)pyridyl]. Catalysis of the oxidation of 3,5-di-tert-butylcatechol to 3,5-di-tert-butylquinone by 1 and 2 was studied. Correlations between the reactivity, chloride substitution behavior, and reduction potentials of both complexes were made. These show that the rate of oxidation is independent of the rate of chloride substitution, indicating that the substitution of chloride by catechol as substrate occurs in a fast step. Spectral data show a non-linear relationship between the ability of the complexes to oxidize 3,5-DTBC and the Lewis acidity of their copper(II) centers. Electrochemical data demonstrate that the most effective complex 1 has a E 0 value that approaches the E 0 value of the natural tyrosinase enzyme.

Electrochemical Study of Esculetin Nitration by Digital Simulation of Cyclic Voltammograms

The reaction of electrochemically generated o‐quinones from oxidation of esculetin as Michael acceptor with nitrite ion as nucleophile has been studied using cyclic voltammetry. The reaction mechanism is believed to be EC, including oxidation of catechol moiety of esculetin followed by Michael addition of nitrite ion. The observed homogeneous rate constants (kobs) for reactions were estimated by comparing the experimental voltammetric responses with the digitally simulated results based on the proposed mechanism. Also the effects of pH and nucleophile concentration on voltammetric behavior and the rate constants of chemical reactions were described.

Mechanistic aspects of ligand substitution on [(H 2 O)(tap) 2 RuORu(tap) 2 (H 2 O)] 2 + {tap=2-(m-tolylazo)pyridine} ion by three glycine-containing dipeptides in aqueous medium at physiological pH

The interaction of the title complex with selected glycine-containing dipeptides(L-L′H) such as glycyl-glycine(L-L1H), glycyl-L-alanine (L-L2H) and glycyl-L-leucine(L-L3H) has been studied spectrophotometrically in aqueous medium as a function of [substrate complex], [ligand] and temperature. The reaction has been monitored at 600 nm where the spectral difference between the reactant and product is a maximum. At pH 7.4, the interaction with studied dipeptides shows two parallel steps. i.e., it shows a non-linear dependence on the concentration of dipeptides; both processes are ligand-dependent. The rate constants for the processes are: k1 ~10 − 3 s − 1 and k 2 ~10 − 5 s − 1. The activation parameters were calculated from Eyring plots. Based on the kinetic and activation parameters an associative interchange mechanism is proposed for the interaction processes. From the temperature dependence of the outer sphere association equilibrium constant, the thermodynamic parameters were also calculated. The product of the reaction has been characterized by IR and ESI-mass spectroscopic analysis. The kinetics of the interaction between [(H2O)(tap)2RuORu(tap)2(H2O)]2+ {tap=2-(m-tolylazo)pyridine} ion and glycine-containing dipeptides such as glycyl-glycine, glycyl-L-alanine and glycyl-L-leucine has been studied spectrophotometrically in aqueous medium as a function of nucleophile concentration, temperature and pH at constant ionic strength. The rate and activation parameters, ESI-mass spectra and IR data were used to deduce a plausible mechanism.

Electrochemical Oxidation of Catechols in the Presence of Dimethyl Phosphite

The reaction of electrochemically generated o-benzoquinones from the oxidation of catechol derivatives as Michael acceptors with dimethyl phosphite as nucleophile has been studied using cyclic voltammetry. The reaction mechanism is believed to be EC comprising oxidation of catechol moiety of these antioxidants followed by Michael addition of dimethyl phosphite. The observed homogeneous rate constants (kobs) for the reactions were estimated by comparing the experimental voltammetric responses with the digitally simulated results based on the proposed mechanism. In addition, the effects of nucleophile concentration and of substitutent group of the catechols on the voltammetric behaviour and the rate constants of the chemical reactions are described.

An efficient route to the synthesis of symmetric and asymmetric diastereomerically pure fullerene triads

A new synthetic route based on the stepwise functionalisation of fullerene cages allows the facile formation of linear, diastereomerically pure triads incorporating two different fullerene cages linked by an organic spacer group. The critical coupling step of two fullerene cages via activation by N,N′-dicyclohexylcarbodiimide was systematically investigated to reveal that the yield of the coupling is maximised in o-dichlorobenzene at high concentrations of the reactant fullerene nucleophile, while in more polar solvents or at lower concentrations of reactants the formation of unwanted side-products (such as guanidine-, N-acylurea- and anhydride-functionalised fullerenes) is favoured. The resultant triads possess an atypically good solubility for this class of compound, which enabled full detailed characterisation by 1H and 13C NMR, IR and UV–vis spectroscopies and by MALDI-TOF mass spectrometry.

Reactivity of a Cytostatic Active N,N-Donor-Containing Dinuclear Pt(II) Complex with Biological Relevant Nucleophiles

A dinuclear platinum(II) complex that was recently investigated in our group was tested for its cytostatic activity and found to be active against HeLa S3 cells. The complex consists of a bidentate N,N-donor chelating ligand system in which the two platinum centers are connected by an aliphatic chain of 10 methylene groups. The complex [Pt(2)(N(1),N(10)-bis(2-pyridylmethyl)-1,10-decanediamine)(OH(2))(4)](4+) (10NNpy) is of further special interest, since only little is known about the substitution behavior of such dinuclear platinum complexes that contain a bidentate coordination sphere. The complex was investigated using different biologically relevant nucleophiles, such as thiourea (tu), L-methionine (L-Met), glutathione (GSH), and guanine-5'-monophosphate (5'-GMP), at two different pH values (2 and 7.4). The substitution of coordinated water by these nucleophiles was studied under pseudo-first-order conditions as a function of nucleophile concentration, temperature, and pressure, using stopped-flow techniques and UV-vis spectroscopy. The reactivity of 10NNpy with the selected nucleophiles was found to be tu ≫ 5'-GMP > L-Met > GSH at pH 2 and GSH > tu > L-Met at pH 7.4. The results for the dinuclear 10NNpy complex were compared to those for the corresponding mononuclear reference complex [Pt(aminomethylpyridine)(OH(2))(2)](2+), Pt(amp), studied before in our group, by which the effect of the addition of an aliphatic chain, an increase in the overall charge, and a shift in the pK(a) values of the coordinated water ligands could be investigated. The reactivity order for Pt(amp) was found to be tu > GSH > L-Met at pH 7.4.

Thermodynamic and kinetic behaviour of [Pt(2-methylthiomethylpyridine)(OH2)2]2+

The diaqua complex [Pt(2-methylthiomethylpyridine)(OH(2))(2)](2+), Pt(mtp), was synthesized and investigated thermodynamically as well as kinetically. Spectrophotometric acid-base titrations were performed to determine the pK(a) values of the two coordinated water ligands. A low pK(a1) value of 3.15 was observed for the water molecule trans to the pyridine donor, whereas a pK(a2) value of 6.84 was found for the water molecule trans to the labilising sulphur donor. The substitution of coordinated water by a series of sterically hindered S-containing nucleophiles, viz. thiourea (tu), N,N'-dimethylthiourea (dmtu) and N,N,N',N'-tetramethylthiourea (tmtu), was studied under pseudo first-order conditions as a function of nucleophile concentration, pH (2, 4.75, 7.4), temperature and pressure, using stopped-flow techniques and UV-vis spectroscopy. In general the first substitution reaction takes place trans to the sulphur donor. At pH 2 the nucleophiles react in the order tu (634 ± 10) > dmtu (507 ± 5) ≫ tmtu (165 ± 3 M(-1) s(-1) at 25 °C), which is caused by steric hindrance. The second observed reaction involves two steps, viz. the displacement of the second water ligand and dechelation of the pyridine ring with the third-order rate constants 73.3 ± 0.8 (tu), 22.1 ± 0.1 (dmtu) and 6.8 ± 0.2 M(-2) s(-1) (tmtu) at 25 °C. At pH 4.75 the reactions are in general slower due to the presence of aqua-hydroxo species. The same order in reactivity was found, viz. tu (106 ± 1) > dmtu (72 ± 1) ≫ tmtu (14.1 ± 0.5 M(-1) s(-1) at 25 °C). No evidence for ring-dechelation could be observed under these conditions. At pH 7.4 the inert dihydroxo species is predominantly present in solution and consequently no substitution reaction was observed. Quantum chemical calculations were performed to support the interpretation and discussion of the experimental results.

Novel Dinuclear Platinum(II) Complexes Containing Mixed Nitrogen–Sulfur Donor Ligands

A series of novel dinuclear platinum(II) complexes were synthesized containing a mixed nitrogen-sulfur donor bidentate chelate system in which the two platinum centers are connected by an aliphatic chain of variable length. The bidentate chelating ligands were selected to stabilize the complex toward decomposition. The pK(a) values and reactivity of the four synthesized complexes, namely, [Pt(2)(S(1),S(4)-bis(2-pyridylmethyl)-1,4-butanedithioether)(OH(2))(4)](4+) (4NSpy), [Pt(2)(S(1),S(6)-bis(2-pyridylmethyl)-1,6-hexanedithioether)(OH(2))(4)](4+) (6NSpy), [Pt(2)(S(1),S(8)-bis(2-pyridylmethyl)-1,8-octanedithioether)(OH(2))(4)](4+) (8NSpy), and [Pt(2)(S(1),S(10)-bis(2-pyridylmethyl)-1,10-decanedithioether)(OH(2))(4)](4+) (10NSpy), were investigated. This system is of special interest because only little is known about the substitution behavior of dinuclear platinum complexes that contain a bidentate chelate that forms part of the aliphatic bridging ligand. Moreover, the ligands as well as the dinuclear complexes were examined in terms of their cytotoxic activity, and the 10NSpy complex was found to be active. Spectrophotometric acid-base titrations were performed to determine the pK(a) values of all the coordinated water molecules. The substitution of coordinated water by thiourea was studied under pseudo-first-order conditions as a function of nucleophile concentration, temperature, and pressure, using stopped-flow techniques and UV-vis spectroscopy. The results for the dinuclear complexes were compared to those for the corresponding mononuclear reference complex [Pt(methylthiomethylpyridine)(OH(2))(2)](2+) (Pt(mtp)), by which the effect of the increasing aliphatic chain length of the bridged complexes could be investigated. The results indicate that there is a clear interaction between the two platinum centers, which becomes weaker as the chain length between the metal centers increases. Furthermore, differences and similarities of the N,S-system were compared to the corresponding dinuclear N,N-system studied previously in our group. In addition, quantum chemical calculations were performed to support the interpretation and discussion of the experimental data.