Solubility kinetic measurements

The second test for the mechanism shown in Scheme 8-8 is to apply equation (c) to (8-10) with kinetic data for dediazoniations with varying concentrations [N2] of molecular nitrogen. As the solubility of N2 is quite low in most solvents, kinetic measurements must be made under N2 pressure. The dediazoniation reaction has a... 

Haag, W. R., and T. Mill, Direct and indirect photolysis of water-soluble azodyes Kinetic measurements and structure-activity relationship , Environ. Toxicol. Chem., 6, 359-369 (1987). 

Kinetics. Kinetic measurements were made by following CO uptake at constant pressure using the apparatus and procedure described earlier (17). The Ru catalyst concentration used was in the range (0.6-6.0) X 10 2A/. Total pressures up to 1 atm and CO partial pressures from 55-590 mm were used. The CO solubility in pure piperidine was 6.5 X 10"3M atm 1 at 21 °C and 5.8 X 10 3M atm 1 at 75°C, Henry s law being obeyed at least up to 1 atm the solubility in toluene was similar (5.7 X 10"3M atm"1 at both 21° and 75°C). The solubility in a toluene-piperidine mixture (1 1 by vol), 5.5 X 10"3Af atm 1 at 75°C was only slightly less than those in the pure solvents. The vapor pressures of piperidine and toluene differ by only about 15-20 mm between 50°-75°C, that of piperidine being the greater (18). Vapor pressure measurements on the solvent mixtures showed that Raoult s Law was obeyed approximately, and the partial CO pressures over toluene-piperidine solutions could be readily estimated. For practical purposes, the partial pressure of piperidine-toluene mixtures, 2.0-10.1M (neat) in piperidine could be taken as that of pure piperidine. 

The thermodynamic and kinetic measurements recently made on the H2S system in natural waters have been critically reviewed. Thermodynamic equations are given for the solubility and ionization of HjS... 

Reaction of dissolved gases in clouds occurs by the sequence gas-phase diffusion, interfacial mass transport, and concurrent aqueous-phase diffusion and reaction. Information required for evaluation of rates of such reactions includes fundamental data such as equilibrium constants, gas solubilities, kinetic rate laws, including dependence on pH and catalysts or inhibitors, diffusion coefficients, and mass-accommodation coefficients, and situational data such as pH and concentrations of reagents and other species influencing reaction rates, liquid-water content, drop size distribution, insolation, temperature, etc. Rate evaluations indicate that aqueous-phase oxidation of S(IV) by H2O2 and O3 can be important for representative conditions. No important aqueous-phase reactions of nitrogen species have been identified. Examination of microscale mass-transport rates indicates that mass transport only rarely limits the rate of in-cloud reaction for representative conditions. Field measurements and studies of reaction kinetics in authentic precipitation samples are consistent with rate evaluations. 

While the activation of H2 to give M-H bonds in soluble metal complexes and their use in homogeneous hydrogenations has been the subject of innumerable investigations and is now well understood, thanks to extensive NMR and IR spectroscopic and kinetic measurements, the actual mechanism of the activation of H2 on a metal surface and its transfer to an organic substrate, although understood in general terms, still lacks some detailed information at the molecular level. 

In Fig. 7 are given the results of kinetic measurements of the latexes given in Fig. 5. It appears that in the case of pure emulsifier the kinetic results are in agreement with common experience in emulsion polymerization of styrene with a water soluble initiator. The rate is approximately constant up to high conversion. 

Detailed kinetic measurements have not been carried out on the soluble allylic compounds from Group IV, V and VI transition metals but rates depend on the transition metal, the presence and number of halogen atoms, and the structure of the allylic grouping [231]. Chromium tris(2-methallyl) was found to be among the more active initiators. Halogen substitution for allyl groups reduced the activity of chromium... 

The anionic polymerization of thiiranes appears to proceed very clearly and in a well defined manner. Living systems have been found and good kinetic measurements have been possible [36]. The base catalysed polymerization of ethylene sulphide (ES) was probably one of the earliest thiirane polymerizations noted. However, the studies have been hindered because the polymer formed is highly crystalline and insoluble. Homogeneous solution studies have not been possible. Propene sulphide (PS) on the other hand gives soluble amorphous polymer and has been amenable to careful study. Indeed the formation of amorphous polypropene sulphide is the major evidence that base catalysed polymerization is ionic and proceeds by the reactions indicated by the equations... 

Kinetic solubilities are by definition very time dependent and as such results can be less reproducible than thermodynamic solubility values. The short timescale also means that they are more dependent on the physical form of the initial precipitate. Consequentially, the correlation between kinetic and thermodynamic solubility is generally poor, with the kinetic measurement usually giving higher values [12, 16]. However, an advantage this can bring is that there will be few compounds excluded as false negatives in this phase. 

Box, K.J., Volgyi, G., Baka, E., Stuart, M., Takacs-Novak, K. and Comer, J.E.A. (2006) Equilibrium versus kinetic measurements of aqueous solubility, and the ability of compounds to supersaturate in solution a validation study. Journal of Pharmaceutical Sciences, 95 (6), 1298-1307. 

The solubility measure describes the concentration reached in solution, when a pure phase of the material is allowed to dissolve in the solvent for a defined period of time, at a defined temperature (and pressure). Most often for pharmaceutical purposes, the pure phase is a solid, ideally a crystalline solid, and the liquid is water or a buffered aqueous solution, at a controlled temperature (often 25 or 37 °C) and ambient pressure. The purity of the solid can have a large effect on measured solubility. Solubility can be measured in water or in pH-controlled buffers. In water, the extent of solubility for ionizable compounds will depend upon the p fCa values and the nature of the counterion. In pH-controlled aqueous buffered solution, at equilibrium, the solubility will depend upon the compound s intrinsic solubility, its plQ, and the ionic strength. It may also depend upon the relative solubility of the initial added compound and the solubility of the salt formed by the compound with the buffer salts, with which the solid may equilibrate. In any buffer or solvent system, the measured solubility may depend on the time of sampling, as solubility kinetics... 

Box ly, Volgyi G, Baka E, Stuart M, Takacs-Novak K, and Comer J. Equilibration Versus Kinetic Measurements of Aqueous Solubility and the Ability of... 

Three common properties that affect intestinal absorption of drugs after oral administration are solubility, permeability, and p/f. Traditional solubility experiments measure solubility of solids placed into aqueous phases (thermodynamic solubility), but these methods are too slow or they consume too much material for drug discovery. Higher throughput methods must be used. The direct ultraviolet (UV) method [17] adds compound dissolved in dimethyl sulfoxide (DMSO) to an aqueous buffer and measures the UV absorption of the aqueous phase using a 96-well plate reader after equilibration and filtration (kinetic solubility). Lipinski has discussed the pitfalls that inadequate solubility information can have for a drug-discovery organization [18]. 

For homogeneous systems, the kinetic parameters k and tq are commonly determined by lab-scale batch experiments in which all reagents are combined at the start of the reaction. Following the concentration of all components (reactants and products) over the course of the reaction then allows for the estimation of the kinetic parameters. Since water has limited solubility in the reaction mixture at the start, conventional kinetic batch experiments could result in erroneous calculation of kj and tq if the limits for homogeneity are crossed. To ensure reaction homogeneity and reliable kinetic measurements, the gradual and continuous addition of water was selected as a suitable method for experimentation (semi-batch mode). The kinetic parameters were then recovered using an appropriate mathematical model with parameter estimation module. 

Substitution reactions of platinum(II) complexes containing one or more metal carbon bond(s) have a long history.217 Interest in such complexes and their reactivity is associated with their function as catalysts in synthetic procedures and in environmental applications. One important characteristic is the kinetic trans effect this is ascribed to the labilisation of a ra/is-positioned group caused by a C-bonded ligand,218 typically alkyl or aryl. In a mechanistic study in which kinetics measurements at elevated pressures were employed, cyclometallated Pt(II) complexes were used.219 The complex shown in Scheme 4 is water-soluble permitting the kinetics of substitution by a wide range of nucleophiles to be studied in aqueous solution. 

Due to the low solubility of the catalyst itself, formation of the dimer appears to be a critical part of the chiral alkylation process since it greatly enhances solubility of the catalyst. Kinetic measurements of the alkylation step revealed an order of 0.5 in catalyst, indicating the dimer dissociates to the monomer before complexation with the indanone enolate. 

Smith °" have demonstrated asymmetric interactions in stereospecific substitution reactions. An estimate of the magnitude of the asymmetric interaction in the case of the d and / form of d.s-[CoCl2(en)2] with the solvent (—)-2,3-butanedioF °, from solubility product measurements, suggests that antiracemisationin systems where solvolytic interference is less important (perhaps with m-[Co(N02)2(en)2] ), will lead to interesting kinetics. In this solvent, as well as 1,2-propanediol, such studies, when compared with the racemisation rates of the resolved complexes in the racemic or meso forms of the solvents, must lead to a greater understanding of the role of the solvent in a class of reactions whose precise mechanism has proved difficult to define. 

It has been, for instance, possible to obtain rate constants, diffusivities and solubilities from measured "mass transfer with chemical reaction" rates in a simple model equipment (9). Nevertheless, there are still controversies on the physicochemical properties and kinetics of some common systems, such as reaction of CO2 with ethanolamines (27,28), and catalyzed oxidation of sodium sulphite (29). Indeed, the kinetics of COo-diethanol-amine reaction still admit room for speculation (28) and certain aspects of COo mass transfer in carbonate solutions have yet to be settled (2/,30). On the other hand, many complex schemes, mostly theoretical, have been analyzed successfully so that selectivities etc. can be predicted. 

This conclusion was confirmed by kinetic measurements. Preparations of purified cytosolic and plastidic phosphorylase isozymes from Pisum sativum were adjusted to an approximately equal activity concentration (as determined at saturating levels of soluble starch). Using these isozyme preparations kinetic measurements were performed at varying levels of the polysaccharide fraction. Orthophosphate or glucose 1-phosphate levels were saturating. The initial rates of phosphorolysis (Fig. 2A) or of polysaccharide biosynthesis (Fig. 2B) were determined. 

Measurements in aqueous electrolyte solutions at elevated temperatures and pressures. By extending kinetic studies to higher temperatures and pressures, the rate constants can be increased to values at which it should be possible to carry out kinetic measurements at potentials near the reversible values, where the anodic and cathodic processes are complementary. From such measurements it should be possible to obtain stoichiometric numbers and complementary reaction orders for the cathodic and anodic processes. Electrode stability and particularly the solubility may prove to be a problem. It also does not necessarily follow that the mechanism and rds will be the same as at lower temperatures. 

Weight loss corrosion rates, which represent an average of corrosion over the test period, are useless from a predictive point of view, but are often used in conjunction with other measurements for quality assessments. Corrosion kinetics can be measured in different ways. Most favored are electrochemical techniques. They are, however, contrary to common belief, indirect techniques and must be properly calibrated and interpreted to be useful. If corrosion products are soluble in solution (as, for instance, iron carbonate), the buildup of such in solution can be used to monitor how corrosion progresses. Hydrogen, a byproduct of anaerobic corrosion, can also be used to monitor kinetics. Less common, but equally direct, are methods that use the removal of radioactivity from irradiated surfaces. Kinetic measurements have also been carried out with electrical resistance probes. As a general principle, no one method is in itself without some problems and should, therefore, always... 

The more soluble a co-crystal is, the greater the risk of failure of kinetic measurements. 

Figure 11.17 Pitfalls of kinetic measurements in assessing co-crystal solubility. The highest maximum concentration is not always associated with the highest solubility. High solubility co-crystals may even elude detection due to a fast transformation rate to drug.

Barclay, L.R.C., Locke, S.J., MacNeil, J.M., VanKessel, J., Burton, G.W. Ingold, K.U. (1984). Autooxidation of micelles and model membranes. Quantitative kinetic measurements can be made by using either water-soluble or lipid-soluble initiators with water-soluble or lipid-soluble chain-breaking antioxidants. Journal of American Chemistry Society, 106, 2479-2481. 

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