Composite Foams of the Graphitic Carbon Nitride@Carbon Nanofibrils Conferred a Superamphiphilic Property and Reinforced Thermal Stability.

Herein, we demonstrated the preparation of novel three-dimensional (3D) superamphiphilic g-C3N4@carbon nanofibers foam (g-C3N4@CNFs) via a two-step approach: liquid nitrogen treatment-freeze-drying; the foams possessed good thermal stability. In this approach, melamine acted as a nitrogen source, and nanofibrillated cellulose (NFCs) functioned as a 3D skeleton. The thermal stability of the as-prepared g-C3N4@CNFs-3 foam was much higher than that of g-C3N4@CNFs-1, as indicated by thermogravimetric data, including an increase of the onset weight loss point (Tonset) by 238.6 °C and an improvement of the maximal weight loss rate (Tmax) by 258.8 °C. The combination of g-C3N4 with CNFs conferred a reduction in the heat release rate (ca. -86%) and the total heat release (ca. -75%). Furthermore, the composition of the hydrophilically oxygenated functional groups and hydrophobic triazine domains in g-C3N4@CNFs rendered it a unique amphiphilic property (contact angle close to 0° within 1.0 s for water and 0° within 12 ms for hexane). A high storage capacity for water and various organic solvents of the superamphiphilic g-C3N4@CNFs foam was found, up to 40-50 times its original weight. The discovery of these superamphiphilic foams is of great significance for the development of superwetting materials and may find their applications in oil emulsion purification and catalyst support fields.

l-Methionine Selenoxide as an Oxidizing and Deprotection Reagent for the Synthesis of Multiple Disulfide Bonds in Peptides.

The regioselective synthesis of multiple disulfide bonds in peptides has been a significant challenge in synthetic peptide chemistry. In this work, two disulfide bonds in peptides were regioselectively synthesized via an approach of MetSeO oxidation and deprotection reaction (SeODR), in which the first disulfide bond was constructed through oxidation of dithiol by MetSeO in a neutral buffer, and the second disulfide bond was then directly constructed through the deprotection of two Acm groups or one Acm group and one Thz group by MetSeO in acidic media. Synthesis of two disulfide bonds by the SeODR approach was achieved through a one-pot manner. Moreover, the SeODR approach is compatible with the synthesis of peptides containing methionine residues. Both H+ and Br- drastically promoted the reaction rate of SeODR. The mechanistic picture for the SeODR approach was delineated, in which the formation of a stable Se-X-S bridge as the transition state plays a critical role. The SeODR approach was also utilized to construct the three disulfide bonds in linaclotide, conferring a reasonable yield.

Deprotection of S-Acetamidomethyl and 1,3-Thiazolidine-4-Carbonyl Protecting Groups from Cysteine Side Chains in Peptides by trans-[PtX2(CN)4]2-: One-Pot Regioselective Synthesis of Disulfide Bonds.

In this study, we developed an efficient approach for disulfide bond formation in peptides utilizing the Pt(IV) complex trans-[PtBr2(CN)4]2- to mediate Acm and Thz deprotections. [PtBr2(CN)4]2- can oxidatively deprotect two Acm groups or deprotect one Thz group and one Acm group to directly form an intramolecular disulfide bond in peptides. Several disulfide-containing peptides with excellent yields were achieved via the deprotection method in an aqueous medium under aerobic conditions. Kinetic studies indicated that the dominant path of the reaction is of first-order in both [Pt(IV)] and [peptide]; moreover, the deprotection rate increased dramatically with the addition of NaBr. A mechanism including a bromide-bridge-mediated electron transfer process was proposed. Apamin, α-conotoxin SI, and the parallel homodimer of oxytocin, all containing two disulfide bonds, were synthesized regioselectively through a one-pot method by the combined use of the above deprotection approach with oxidants l-methionine selenoxide and [PtBr2(CN)4]2-. All of the reactions were completed within 30 min to afford good yields for these peptides.

Mass spectral and theoretical investigations of N-Cα bond cleavages in the disulfide-containing peptide TTCPYCKK and its analogues.

RATIONALE: For disulfide-containing peptides, mass spectrometric analyses are rarely comparably studied between their dithiol and disulfide forms. Persulfide ions afforded from peptides with a disulfide ring are from either an unusual N-Cα bond cleavage or a canonical peptide bond cleavage; their isomeric structures are, however, not identified just from peaks of mass spectra. METHODS: Isomeric structures of [C3 P4 X5 |C6 M ], [C3 MA P4 X5 |C6 MB ] and [P4 X5 C6 |C3 M ] were identified from a series of the X5 substituted dicysteine octapeptides using electrospray ionization tandem mass spectrometry for both their dithiol and disulfide forms. Formation mechanisms of different persulfide ions were investigated systematically by theoretical methods. Moreover, electrostatic potential-mapped molecular van der Waals surfaces were used to determine the stabilities of the intermediates, which gave a further evaluation of favored bond cleavage. RESULTS: Mass spectral analyses indicated that the fragmented ions changed largely when an intramolecular disulfide bond was formed. New types of disulfide-containing fragmented ions [C3 P4 X5 |C6 M ] or [C3 MA P4 X5 |C6 MB ] were thus proposed. Energy analysis showed that the N-Cα cleavage was not competitive energetically with that of the amide bond for Y5 and its phosphorylated analogue. However, the N-Cα cleavage products dominated for the S5 - and T5 -containing peptides. Stabilities of the intermediates were found to be related with the electrostatic potential-mapped molecular van der Waals surfaces. CONCLUSIONS: Persulfide ions containing more residues than previously found were proposed not only from b7 ions but also from y6 ions. In addition, a new kind of phosphorylated analogue, [C3 P4 p Y5 |C6 M ], is reported in this work. Our study provides convincing results for separating isomeric structures in the cases of N-Cα cleavages, which greatly assists in the structural identification of disulfide-containing peptides.

Investigations of the Kinetics and Mechanism of Reduction of a Carboplatin Pt(IV) Prodrug by the Major Small-Molecule Reductants in Human Plasma.

The development of Pt(IV) anticancer prodrugs to overcome the detrimental side effects of Pt(II)-based anticancer drugs is of current interest. The kinetics and reaction mechanisms of the reductive activation of the carboplatin Pt(IV) prodrug cis,trans-[Pt(cbdca)(NH3)2Cl2] (cbdca = cyclobutane-1,1-dicarboxylate) by the major small-molecule reductants in human plasma were analyzed in this work. The reductants included ascorbate (Asc), the thiol-containing molecules L-cysteine (Cys), DL-homocysteine (Hcy), and glutathione (GSH), and the dipeptide Cys-Gly. Overall second-order kinetics were established in all cases. At the physiological pH of 7.4, the observed second-order rate constants k' followed the order Asc << Cys-Gly ~ Hcy < GSH < Cys. This reactivity order together with the abundances of the reductants in human plasma indicated Cys as the major small-molecule reductant in vivo, followed by GSH and ascorbate, whereas Hcy is much less important. In the cases of Cys and GSH, detailed reaction mechanisms and the reactivity of the various protolytic species at physiological pH were derived. The rate constants of the rate-determining steps were evaluated, allowing the construction of reactivity-versus-pH distribution diagrams for Cys and GSH. The diagrams unraveled that species III of Cys (-SCH2CH(NH3+)COO-) and species IV of GSH (-OOCCH(NH3+)CH2CH2CONHCH(CH2S-)- CONHCH2COO-) were exclusively dominant in the reduction process. These two species are anticipated to be of pivotal importance in the reduction of other types of Pt(IV) prodrugs as well.

Reactivity of the glutathione species towards the reduction of ormaplatin (or tetraplatin).

The reduction of ormaplatin (tetraplatin), a prototype for Pt(IV) anticancer prodrugs, by glutathione (GSH) was kinetically characterized over a wide pH range at 25.0°C and 1.0M ionic strength. The reduction follows overall second-order kinetics, giving rise to the oxidized glutathione as the oxidation product, which was identified by high-resolution mass spectrometry. The reaction mechanism put forward involves parallel attacks by all the GSH species on the Pt(IV) prodrug as rate-determining steps. All rate constants for the rate-determining steps have been derived for the first time, enabling the construction of the reactivity of GSH species versus their pH distribution diagram. The diagram clearly displays that only one out of the five GSH species is the mainly responsible for the reduction of ormaplatin at the physiological pH of 7.4.

Novel assaying method for the accurate and rapid analysis of antioxidant total capacity based on hexachloroiridate(IV).

We introduce a novel method, namely IrRAC, for assessing total antioxidant capacity utilizing the single electron oxidant hexachloroiridate(IV). This method leverages the 488 nm absorption band of [IrCl6]2- largely reducing interferences from antioxidants and their oxidation products. [IrCl6]2- is stable 6 h in phosphate-buffered saline (PBS) ensuring consistent and reproducible absorbance readings and rendering spectrophotometric determinations under physiological neutrality. Individual assessments of 23 antioxidants reveal a linear correlation between decreasing absorbance and increasing antioxidant concentration. When the IrRAC assay was compared with several established water-based methods, strong correlations were found. Importantly, [IrCl6]2- shows a minimal oxidation of non-antioxidative substances. Moreover, IrRAC performs well with synthetic antioxidant mixtures and real samples, highlighting that the nature of antioxidants dominates the assay without much disturbance. Commercial availability of K2[IrCl6] eliminates the need of pretreatment of the oxidant. Undoubtedly, the new method confers a compelling and cost-effective alternative to the existing electron transfer-based methodologies.

Effective assessment of lanthanide ion delivery into live cells by paramagnetic NMR spectroscopy.

We report an effective assessment of lanthanide ion (Ln3+) delivery into live cells by paramagnetic NMR spectroscopy. Free Ln3+ ions are toxic to live cells resulting in a gradual leakage of target proteins to the extracellular media. The citrate-Ln3+ complex is an efficient and mild reagent over the free Ln3+ form for live cell delivery.

PEC thrombin aptasensor based on Ag-Ag2S decorated hematite photoanode with signal-down effect of precipitation catalyzed by G-quadruplexes/hemin.

A photoelectrochemical (PEC) aptasensor for thrombin detection was rationally designed based on the photoanode of one-dimensional hematite nanorods (α-Fe2O3 NRs) with several steps of modifications. Uniform α-Fe2O3 NRs were grown vertically on the surface of fluorine-doped tin oxide (FTO) conductive glass through a one-step hydrothermal method; then Ag was grown on the surface of α-Fe2O3 NRs through a photoreduction method followed by a partial in-situ transformation into Ag2S, conferring an improvement on the initial photocurrent. Two main critical factors, namely, the steric hindrance of thrombin, benzoquinone (BQ) precipitation oxidized by H2O2 under the catalysis of G-quadruplexes/hemin, contributed to the sensitive signal-down response toward the target. Photocurrent signals related with thrombin concentration was established for thrombin analysis due to the non-conductive complex as well as their competitive consumption of electron donors and irradiation light. The excellent initial photocurrent was combined with the signal-down amplification in the design of the biosensor, conferring a limit of detection (LOD) as low as 40.2 fM and a wide linear range from 0.0001 nM to 50 nM for the detection of thrombin. The proposed biosensor was also assessed in terms of selectivity, stability, and applicability in human serum analyses, which provided an appealing maneuver for the specific analysis of thrombin in trace amount.

Hierarchically supramolecular polymerization of anthraquinone dye to chiral aggregates via 2D-monolayered nanosheets: the unanticipated role of pathway complexity.

An anthraquinone dye underwent supramolecular polymerization, affording 2D-monolayered nanosheets in a kinetically controlled state. The nanosheets then transformed into hierarchically chiral aggregates in a thermodynamically controlled step. The unanticipated role played by pathway complexity was clearly unravelled in this work, highlighting the diversified pathways in the supramolecular polymerization of various building blocks.

Synthesis of the Magnetically Nanoporous Organic Polymer Fe3O4@SiO2-NH2-COP and Its Application in the Determination of Sulfonamide Residues in Surface Water Surrounding a Cattle Farm.

Efficient extractions of trace antibiotic residues in the environment are a key factor for accurate quantification of the residues. A new nanoporous material, namely, magnetically covalent organic polymer (MCOP, Fe3O4@SiO2-NH2-COP) was synthesized in this work and was used for magnetic solid-phase extraction (MSPE). The combination of MSPE with high-performance liquid chromatography separation together with ultraviolet detection (HPLC-UV) was established as an effective method for the determination of four sulfonamide (SA) residues in surface water surrounding a cattle farm. The synthesized magnetic material was characterized by SEM, TEM, FT-IR, magnetic properties measurement system (MPMS), and nitrogen gas porosimetry. The material possessed many attractive features, such as a unique microporous structure, a larger specific surface area (137.93 m2·g-1) than bare Fe3O4 (24.84 m2·g-1), high saturation magnetization (50.5 emu·g-1), open adsorption sites, and high stability. The influencing parameters, including pH, the used amount of MCOPs, the type of eluent, adsorption solution, and desorption time, were optimized. Under the optimized conditions, the method conferred good linearity ranges (R 2 ≥ 0.9990), low detection limits (S/N = 3, LOD, 0.10-0.25 µg·L-1), and satisfactory recoveries (79.7% to 92.2%). The enrichment factor (EF) for the four SAs was 34.13-38.86. The relative standard deviations of intraday (n = 5) and of interday (n = 3) were less than 4.8% and 8.9%, respectively. The equilibria between extraction and desorption for SAs could be reached within 150 s. The proposed method was sensitive and convenient for detecting SA residues in complex environmental matrices, and the successful application of the new MCOPs as an adsorbent was demonstrated.

Mass spectral and theoretical investigations of the transient proton-bound dimers on the cleavage processes of the peptide GHK and its analogues.

Fragmentation mechanisms of the singly protonated peptides GHK, GHKH and HGHK have been investigated by mass spectrometry and theoretical calculations. Fragmentation behavior of the protonated H-K amide bond in GHK was changed completely when a histidinyl residue was introduced into the C-terminus of GHK. The H-K amide bond breaking was a predominant pathway in the case of GHK and GHKH. For HGHK, the histidinyl residue at the N-terminus hampered significantly breaking of the H-K amide bond resulting in a high potential energy barrier; calculations indicated that this histidinyl effect played a vital role for the H-K amide bond fragmentation. Subsequent analysis of the fragmentation mechanism revealed that recombination processes of the hydrogen bonding for the intermediate products were all exergonic. Formation of a proton-bound dimer (PBD) lowering the energy barriers from a thermodynamic perspective for all the designed fragmentation pathways was demonstrated to be feasible by our systematic calculations. Moreover, the involvement of different PBDs was further confirmed by analyses of the reduced density gradient (RDG) isosurfaces and scatter maps. A dynamically favored pathway was likely via six-membered ring or nine-membered ring structures generated by the diketopiperazine as revealed by atom-in-molecules (AIM) analyses, since the steric interaction energies in the newly formed ring were estimated to be relatively small when compared to the products generated from a lactam and/or an oxazolone pathway. This is the first feasibility investigation from a dynamic viewpoint for formation of different rings involved in the lactam, oxazolone or diketopiperazine pathways in the fragmentation mechanisms proposed.

Insight into nucleophilic fragmentation mechanisms by glutamic acid side chain in singly protonated glutathione and related peptidyl ions.

Fragmentation mechanisms of the singly protonated glutathione (γ-ECG) and its synthetic analogue peptides (ECG and PPECG) have been investigated by liquid chromatography tandem-mass spectrometry and theoretical calculations. In the mass spectra, similar fragmentation patterns were observed for γ-ECG and ECG, but a completely different one was found in the case of PPECG. The E-C amide bond cleavage is the predominant pathway for the fragmentation of γ-ECG and ECG, whereas the additional N-terminal prolyl residues in PPECG significantly suppress the E-C amide bond cleavage. Theoretical calculations reveal that the fragmentation efficiencies of the E-C bonds in the protonated γ-ECG and ECG are much higher than that in the protonated PPECG, being attributed to their lower barriers of the potential energy; clearly the introduction of two prolyl residues can increase substantially the potential energy barrier. In the proposed mechanism, the protonated E-C amide bonds in the three peptides are first weakened followed by a nucleophilic addition by the glutamyl carboxyl oxygen atom in side chain, leading to the breaking of the E-C amide bonds. However, the processes of E-C bond fragmentation for three protonated analogs were not collaborative. Protonated amide bonds first fragment, then the nucleophilic addition by the side chain of glutamyl carboxyl oxygen atom takes places. On the other hand, the prolyl residues in PPECG can largely diminish the nucleophilic addition, resulting in a much lower efficiency of its E-C amide bond breaking. Distance analysis indicates that breaking the E-C amide bonds in the protonated γ-ECG, ECG, and PPECG ions could not occur without the assistance from the nucleophilic attack, highlighting an asynchronous collaborative process in the bond breakings.

Spectroscopic, kinetic, and theoretical analyses of oxidation of dl-ethionine by Pt(IV) anticancer model compounds.

Ethionine is an S-ethyl analog of methionine (Met) having a small change in structure. But it is a chemical carcinogen and an antagonist of Met, thus displaying a disparate biological profile. The oxidations of ethionine by biologically important oxidants have not been exploited. Oxidations of dl-ethionine by Pt(IV) anticancer model complexes trans-[PtX2(CN4)]2- (X = Cl or Br) were thus analyzed by time-resolved and stopped-flow spectral techniques. Overall second-order kinetics was established, being first-order in [Pt(IV)] and [Ethionine]tot (the total concentration of ethionine); the observed second-order rate constant k' versus pH profiles were obtained. A stoichiometry of Δ[Pt(IV)]:Δ[Ethionine]tot = 1:1 was unraveled, indicating that ethionine was oxidized to ethionine-sulfoxide which was confirmed by NMR spectroscopic and high-resolution mass spectral analyses. In the proposed reaction mechanism which is similar to that for the oxidation of Met by the same Pt(IV) compounds, the rate-determining steps are rationalized in terms of a bridge formation between one of the coordinated halides in [PtX2(CN4)]2- and the sulfur atom in ethionine, followed by an X+ transfer. Moreover, a large rate enhancement for the reaction of ethionine with [PtBr2(CN4)]2- compared with [PtCl2(CN4)]2- strongly supports an X+ transfer mechanism. Furthermore, a combined quantum-mechanical/molecular-mechanical (QM/MM) method was utilized to simulate a Cl+ transfer mechanism from trans-[PtCl2(CN)4]2- to ethionine. The simulations unraveled the energetically stable structures of reactants and products, which favor the Cl+ transfer process. Rate constants of the rate-determining steps have been derived. Ratios of k (ethionine)/k (Met) are between 2.2 and 2.6 obtained for the three protolytic species of ethionine and Met; the enhanced reactivity might be partially responsible for the disparate biological profiles.

Reduction of ormaplatin by an extended series of thiols unravels a remarkable correlation.

Ormaplatin ([Pt(dach)Cl4]) represents one of the three primary structural prototypes of Pt(iv) anticancer-active prodrugs. The reduction of ormaplatin by an extended series of thiols has been studied kinetically in a broad pH range. A novel and remarkable correlation between log kRS- and the thiol dissociation constants pKRSH is disclosed: log kRS- = (0.50 ± 0.02)pKRSH + (0.68 ± 0.13), where kRS- denotes the second-order rate constant of each thiolate towards the reduction of ormaplatin.

Kinetics and mechanism of oxidation of the anti-tubercular prodrug isoniazid and its analog by iridium(iv) as models for biological redox systems.

A complex reaction mechanism of oxidation of the anti-tubercular prodrug isoniazid (isonicotinic hydrazide, INH) by [IrCl6]2- as a model for redox processes of such drugs in biological systems has been studied in aqueous solution as a function of pH between 0 and 8.5. Similar experiments have been performed with its isomer nicotinic hydrazide (NH). All reactions are overall second-order, first-order in [IrCl6]2- and hydrazide, and the observed second-order rate constants k' have been determined as a function of pH. Spectrophotometric titrations indicate a stoichiometry of [Ir(iv)] : [hydrazide] = 4 : 1. HPLC analysis shows that the oxidation product of INH is isonicotinic acid. The derived reaction mechanism, based on rate law, time-resolved spectra and stoichiometry, involves parallel attacks by [IrCl6]2- on all four protolytic species of INH and NH as rate-determining steps, depending on pH. These steps are proposed to generate two types of hydrazyl free radicals. These radicals react further in three rapid consecutive processes, leading to the final oxidation products. Rate constants for the rate-determining steps have been determined for all protolytic species I-IV of INH and NH. They are used to calculate reactivity-pH diagrams. These diagrams demonstrate that for both systems, species IV is ca. 105 times more reactive in the redox process than the predominant species III at the physiological pH of 7.4. Thus, species IV will be the main reactant, in spite of the fact that its concentration at this pH is extremely low, a fact that has not been considered in previous work. The results indicate that pH changes might be an important factor in the activation process of INH in biological systems also, and that in such systems this process most likely is more complicated than previously assumed.

Reduction of ormaplatin and cis-diamminetetrachloroplatinum(iv) by ascorbic acid and dominant thiols in human plasma: kinetic and mechanistic analyses.

The reductions of Pt(iv) anticancer prodrugs [Pt(dach)Cl4] (ormaplatin/tetraplatin), cis-[Pt(NH3)2Cl4], and cis,cis,trans-[Pt(NH3)2Cl2Br2] by the several dominant reductants in human plasma have been characterized kinetically in this work, including l-ascorbic acid (Asc), l-glutathione (GSH), l-cysteine (Cys), dl-homocysteine (Hcy), and a dipeptide Gly-Cys. All the reductions follow an overall second-order kinetics, being first-order each in [Pt(iv)] and in the [reductant]. A general reactivity trend of Asc < Hcy < Cys-Gly < GSH < Cys is clearly revealed for the reductions of [Pt(dach)Cl4] and [Pt(NH3)2Cl4] at 37.0 °C and pH 7.40. Analysis of the observed second-order rate constants k' implies that these Pt(iv) prodrugs have a very short lifetime (less than a minute) in human plasma and can hardly enter into cells before reduction and that Asc might not play a dominant role in the reduction process among the reductants. The reductions of [Pt(dach)Cl4] and [Pt(NH3)2Cl4] by Asc have been studied in a wide pH range, and a reaction mechanism has been proposed involving parallel reductions of the Pt(iv) complexes by the Asc protolytic species. Moreover, a halide-bridged (inner-sphere) electron transfer mode for the rate-determining steps is discussed in detail; several lines of evidence strongly bolster this type of electron transfer. Furthermore, the observed activation parameters corresponding to k' have been measured around pH 7.40. Analysis of the established k'-pH profiles indicates that k' is a composite of at least three parameters in the pH range of 5.74-7.40 and the measured activation parameters in this range do not correspond to a single rate-determining step. Consequently, the isokinetic relationship reported previously using the measured ΔH(‡) and ΔS(‡) in the above pH range might be an artifact since the relationship is not justified anymore when our new data are added.

One-pot preparation of a novel monolith for high performance liquid chromatography applications.

Various novel porous organic-based monoliths with the mode of hydrophobicity were synthesized by in situ free-radical crosslinking copolymerization and optimized for the separations of small molecules and high-performance reversed-phase chromatography (RP-chromatography). These monoliths contained co-polymers based on glycidyl methacrylate (GMA)/ethylene glycol dimethacrylate (EDMA)/tripropylene glycol diacrylate (TPGDA) or EDMA/TPGDA. A mixture of cetanol, methanol and poly (ethylene glycol) (PEG) was used as the porogen, with the ratio of these solvents being varied along with the polymerization temperature to generate a library of monoliths. The conditions were optimized and the resulting poly (GMA-co-TPGDA-co-EDMA) monolith was investigated by infrared spectrometer (IR), field emission scanning electron microscope (FESEM), and mercury intrusion porosimetry (MIP), respectively. The column performance was assessed by the separation of a series of neutral solutes of benzene derivatives. The result demonstrated that the prepared monolith exhibited an RP-chromatographic behavior and relatively homogeneous structure, good permeability and separation performance. Moreover, the relative standard deviations (RSDs) of the retention factor values for benzene derivatives were less than 1.5% (n=7, column-to-column). The approach used in this study was extended to the separation of anilines.

trans-Dichlorotetracyanoplatinate(IV) as a Reagent for the Rapid and Quantitative Formation of Intramolecular Disulfide Bonds in Peptides.

Oxidation of cysteine thiol groups by trans-dichlorotetracyanoplatinate(IV) to form intramolecular peptide disulfide bonds has been studied for a series of dithiol peptides ranging from 4 to 15 amino acid residues in length. The dithiol peptides are rapidly and quantitatively transformed to their intramolecular disulfide forms by a slight excess of [Pt(CN)(4)Cl(2)](2)(-), as shown by HPLC. Quantitative analyses by HPLC and by spectrophotometric titration confirm a [Pt(IV)]:[dithiol peptide] stoichiometry of 1:1. Under the low pH conditions used, oxidation to form a 38-membered ring in the case of reduced somatostatin is as rapid as that to form much smaller rings, suggesting that ring closure is not the rate-determining step. The oxidation rates increase as the pH is increased. Time-resolved spectra show two isosbestic points, indicating that no peptide-platinum intermediates accumulate to a significant amount. A reaction mechanism similar to that for reduction of [Pt(CN)(4)Cl(2)](2)(-) by monothiols is proposed. [Pt(CN)(4)Cl(2)](2)(-) is a mild oxidant and essentially substitution inert; its reduction product, [Pt(CN)(4)](2)(-), is stable, has no redox chemistry with peptides, and does not form complexes with peptides. Moreover, [Pt(CN)(4)Cl(2)](2)(-) and [Pt(CN)(4)](2)(-) are nontoxic and readily separable from peptides by HPLC, and the cost of the Pt(IV) complex is negligible compared with that of peptides. The only unwanted side reaction observed with [Pt(CN)(4)Cl(2)](2)(-) is oxidation of the sulfur of methionine to the sulfoxide form. These characteristics and the results of this study suggest that [Pt(CN)(4)Cl(2)](2)(-) is an excellent reagent for the formation of intramolecular peptide disulfide bonds.

Kinetics and Mechanism for Formation of Olefin Complexes in the Reaction between Palladium(II) and Maleic Acid.

Complex formation between Pd(H(2)O)(4)(2+) and maleic acid (H(2)A) has been studied at 25 degrees C and 2.00 M ionic strength in acidic aqueous solution. Reaction takes place with 1:1 stoichiometry. The kinetics has been followed by use of stopped-flow spectrophotometry under pseudo-first-order conditions with maleic acid in excess. In the concentration ranges 0.01 C where, in addition, both steps contain contributions from parallel reactions. The amplitude of the first phase increases with increasing [H(2)A](tot) and with decreasing [H(+)]. Multiwavelength global analysis of the kinetic traces and the UV-vis spectral changes suggest that a monodentate oxygen-bonded hydrogen maleate complex, [Pd(H(2)O)(3)OOCCH=CHCOOH](+), B, with stability constant K(2) = 205 +/- 40 M(-)(1) is formed as an intermediate in this first step via two parallel reversible reactions in which Pd(H(2)O)(4)(2+) reacts with maleic acid and hydrogen maleate, respectively. In the following step, B --> C, slow intramolecular ring closure with a rate constant of 0.8 +/- 0.1 s(-)(1) at 25 degrees C gives the reaction product C, which is concluded to be a 4.5-membered olefin-carboxylato chelate complex on the basis of stoichiometry and UV-vis/NMR spectra. Parallel and irreversible attack by maleic acid and hydrogen maleate acting as olefins on the intermediate B also leads to formation of C. C is stable for at least 20 h for concentrations of