Arrhenius Parameters Research Articles

Determining Free‐Radical Propagation Rate Coefficients with High‐Frequency Lasers: Current Status and Future Perspectives

Detailed knowledge of the polymerization mechanisms and kinetics of academically and industrially relevant monomers is mandatory for the precision synthesis of tailor-made polymers. The IUPAC-recommended pulsed-laser polymerization-size exclusion chromatography (PLP-SEC) approach is the method of choice for the determination of propagation rate coefficients and the associated Arrhenius parameters for free radical polymerization processes. With regard to specific monomer classes-such as acrylate-type monomers, which are very important from a materials point of view-high laser frequencies of up to 500 Hz are mandatory to prevent the formation of mid-chain radicals and the occurrence of chain-breaking events by chain transfer, if industrially relevant temperatures are to be reached and wide temperature ranges are to be explored (up to 70 °C). Herein the progress and state-of-the-art of high-frequency PLP-SEC with pulse repetition rates of 500 Hz is reported, with a critical collection of to-date investigated 500 Hz data as well as future perspectives for the field.

Diffusionless nature of D03 → L12 transition in Fe3Ga alloys

Temperature dependent internal friction is studied in an Fe3Ga alloy using a dynamical mechanical analyzer. Apart from several thermally activated relaxation peaks with the Arrhenius parameters (activation energies of 1.05 and 1.85 eV and a pre-factor τ0 ≈ 10−15s) featuring a Snoek-type and Zener relaxation, respectively, a transient internal friction peak related to a structural transition upon heating is found and analyzed in detail. This peak substantiates an irreversible transition from a D03 ordered bcc to an L12 ordered fcc lattice, as further confirmed by in situ X-ray diffraction measurements. The transient peak is unambiguously shown to feature a diffusionless phase transition.

Combustion Kinetics of Biochar from Fast Pyrolysis of Pine Sawdust: Isoconversional Analysis

Non-isothermal thermogravimetric data were used to evaluate the Arrhenius parameters (activation energy and the pre-exponential factor) of the combustion of biochar. The biochar was produced as a byproduct from the fast pyrolysis of pine sawdust particle. The isoconversional methods (Kissinger–Akahira–Sunose and Flynn–Wall–Ozawa method) were used for evaluating the activation energy and the kinetic model function f(α), which was determined by using the master plot method. The effective activation energy for combustion of biochar was 212.524 kJ mol–1 in the conversion range of 0.15–0.85. The results showed that the most probable mechanism is the simple order reaction model function, f(α) = (1 – α)3.3, and A = 6.20 × 1012 s–1.

Nb and Ta diffusion in titanite

Chemical diffusion of Nb and Ta under anhydrous, pO2-buffered conditions has been measured in natural titanite. The source of diffusants were mixtures of CaSiO3, TiO2, and Al2O3 powders, with either Nb or Ta oxides added. Experiments were run in evacuated sealed silica glass ampoules with solid buffers (buffered at NNO). Rutherford Backscattering Spectrometry (RBS) was used to measure Nb and Ta concentration profiles. The following Arrhenius parameters were obtained for Nb and Ta diffusion parallel to c over the temperature range 850–1252°C under NNO-buffered conditions:DNb=3.23×10−9exp−299±12kJmol−1/RTm2s−1DTa=4.34×10−10exp−281±10kJmol−1/RTm2s−1.In contrast to the findings of Marschall et al. (2013) for rutile, there do not appear to be large differences between Ta and Nb diffusivities in titanite, so the likelihood of diffusive fractionation of these elements will not be great. Values for diffusion coefficients measured parallel to the a-axis for both elements are similar to those parallel to c, indicating that Nb and Ta diffusivities in titanite do not exhibit significant anisotropy. Nb and Ta diffusion in rutile is faster than diffusion of these elements in titanite at higher temperatures (by about 2 and 1.5 orders of magnitude at 700°C for Nb and Ta, respectively), but because of the higher activation energies for diffusion of Nb and Ta in rutile, they will approach values for titanite with decreasing T. These diffusion data indicate that titanite should be moderately retentive of Nb and Ta chemical signatures, with diffusivities slower than those for Zr, O and Pb in titanite, but faster than those for the REE under most geologic conditions. These differences among diffusivities suggest that information derived from Zr thermometry, U–Pb geochronology, and geochemical tracers such as Ta, Nb and the REE may be decoupled in titanite under some conditions.

Mechanistic analysis of ultrasound assisted enzymatic desulfurization of liquid fuels using horseradish peroxidase

This study has attempted to gain physical insight into ultrasound-assisted enzymatic desulfurization using system comprising horseradish peroxidase enzyme and dibenzothiophene (DBT). Desulfurization pathway (comprising DBT-sulfoxide and DBT-sulfone as intermediates and 4-methoxy benzoic acid as final product) has been established with GC–MS analysis. Intrinsic fluorescence and circular dichroism spectra of ultrasound-treated enzyme reveal conformational changes in secondary structure (reduction in α-helix and β-conformations and increase in random coil content) leading to enhancement in activity. Concurrent analysis of desulfurization profiles, Arrhenius and thermodynamic parameters, and simulations of cavitation bubble dynamics reveal that strong micro-convection generated by sonication enhances enzyme activity and desulfurization kinetics. Parallel oxidation of DBT by radicals generated from transient cavitation gives further boost to desulfurization kinetics. However, random motion of enzyme molecules induced by shock waves reduces frequency factor and limits the ultrasonic enhancement of enzymatic desulfurization.

An advanced reaction model determination methodology in solid-state kinetics based on Arrhenius parameters variation

An advanced reaction model determination methodology in solid-state kinetics based on Arrhenius parameters variation

Group Additive Kinetics for Hydrogen Transfer Between Oxygenates.

Hydrogen abstraction reactions involving oxygenates in gaseous phase play an important role in many biomass-related conversion processes. In this work, group additivity is used to provide Arrhenius parameters in a temperature range of 300-2500 K for hydrogen abstractions between oxygenate compounds such as alcohols, ethers, esters, acids, ketones, diketones, aldehydes, hydroxyperoxides, alkyl peroxides, and unsaturated ethers and ketones. The group additive values for Arrhenius parameters of hydrogen transfer reactions of the type O--H--C and O--H--O are derived from CBS-QB3 calculations in the high-pressure limit. From a total set of 118 reactions, 43 group additivity values are determined. Inclusion of an additional 37 corrections accounting for cross-resonance effects in the transition state further improves the accuracy of the model. For a set of 25 ab initio calculated and 60 experimental rate coefficients, group additive modeling reproduces rate coefficients within a mean factor of deviation of ∼3. Hence, the developed group additive models can be reliably used for an accurate and fast prediction of the kinetics of hydrogen abstractions involving oxygenates.

Application of dhurrin for kinetics and thermodynamic characterization of linamarase (β-glucosidase) genetically engineered from Saccharomyces cerevisiae.

Recombinant Saccharomyces cerevisiae cells at the stationary phase of growth were recovered, homogenized and centrifuged to obtain crude extracts designated as GELIN 0 . Carboxy methyl cellulose, diethyl amino-ethyl-sephadex and diethyl amino-ethyl-cellulose were used to purify the crude extracts of GELIN 0 resulting in GELIN 1 , GELIN 2 and GELIN 3 , respectively. The ability of the enzyme extracts and a commercial native linamarase (CNLIN) to hydrolyse cyanogenic glucosides was challenged using dhurrin from sorghum as substrate. Precisely, the actions of commercial native linamarase (CNLIN) and the genetically engineered linamarase (β-glucosidase) from Saccharomyces cerevisiae on dhurrin as influenced by degree of its purification, pH (6.8 ) and temperature(30-45°C) were investigated and the data derived were applied for kinetics and thermodynamic characterization of the enzymes. Enzymic degradation kinetics of the dhurrin were evaluated using a 4 x 6 x 8 B/W design comprising of 4 enzyme types ( GELIN o , GELIN 1 GELIN 2 and GELIN 3 ,, 6 temperatures (30, 32, 35, 37, 40, 45 °C) and 8 time intervals( 0-70 min.). Data obtained from the residual HCN with time were fitted into zero, first and second order kinetics models to derive reaction rate constant (Kmin -1 ) values which were analyzed using the Arrhenius and absolute reaction rate models Thermodynamic parameters were obtained including; activation energies (E a ), frequency factor(K o ), enthalpy (ΔH ) and entropy (ΔS#) that characterized the reactions on dhurrin catalyzed by commercial native linamarase (CNLIN) and the genetically engineered linamarase (β-glucosidase) from Saccharomyces cerevisiae. The results showed that the best fitted order based on higher coefficient of linear regression (r 2 ) values > 0.998 and linearity of curves was the first order kinetics model and not either zero or second order models. Kmin -1 values ranged from GELIN O- GELIN 3 0.03-0.07 μmol/min while the derived D-values from K-values were in the range of 24-65 min. The frequency factors (K o ) increased with enzyme purity from GELIN 0 to GELIN 3 corresponding to K o (min -1 ) of 22.585 to 56.462. The energy of activation E a (KJ/mol)generated 60.0995 to 150.6900 corresponding to enzymes GELIN 0 to GELIN 3 followed the same pattern with frequency factor for breaking of bonds in dhurrin molecules. At pH 6.8 CNLIN showed no action on dhurrin. The high correlation coefficient values of (r 2 = 0.97 to 0.99) indicated the best fit of the Arrhenius and the absolute reaction rate models. The entropy change (ΔS) increased with enzyme purity from 0.588 J/mol.deg. to 1.4625Jmol degree. The enthalpy change KJ/mol followed the same pattern whereby increases influenced by enzyme purity ranged from 1892 KJ/mol to 13104KJ/mol. Keywords : kinetics, thermodynamic, characterization, dhurrin, genetically engineered β- glucosidase, Saccharomyces cerevisiae.

No Apparent Correlation of kp with Steric Hindrance for Branched Acrylates

The Arrhenius parameters of the propagation rate coefficient, kp, are determined via the pulsed laser polymerization—size exclusion chromatography (PLP‐SEC) method for five branched acrylates (tert‐butyl (tBA), isobornyl (iBoA), benzyl (BnA), 2‐ethylhexyl (EHA), and 2‐propylheptyl acrylate (PHA)) in 1 m solution in butyl acetate (BuAc) to complete the series, published by Haehnel et al. in 2014, of branched acrylates (isononyl (INA‐A), tridecyl (TDA‐A and TDN‐A), heptadecyl (C17A), and henicosyl acrylate (C21A)) in solution that do not show a trend in kp. Furthermore, the propagation rate coefficients of the branched acrylates in 1 m solution are critically compared with the branched acrylates in bulk as well as branched methacrylates. A summary of the trends and family‐type behavior for the linear and branched (meth)acrylates as well as methacrylates with cyclic ester side chains is provided. For the branched acrylates in 1 m solution, no clear trends of the propagation rate coefficients, kp, or Arrhenius parameters A and EA are detectable and—in contrast to the corresponding methacrylates—there is no family‐type behavior observed in solution as well as in bulk.image

On the way from the activation model of solid decomposition to the thermochemical model

The development of the technology and the theory of electrothermal atomization, which began in atomic absorption spectrometry about 60 years ago, led to a confrontation between the two alternative models used in the kinetics of heterogeneous chemical reactions: the activation model proposed by Arrhenius (Z Phys Chem 4:226–248, 1889) and based on the effect of activation, and the thermochemical model (TM) proposed by Langmuir (Phys Rev 2:329–342, 1913), which excludes the existence of this effect. An analysis of the events surrounding the creation and evolution of both models and a comparison of their fundamental principles and their application to the solution of actual problems show the shortcomings of the activation model and fundamental limitations in its applicability. The TM for the first time in the history of these studies allowed a quantitative estimation and a prediction of the lifetime for substances depending on the environment and temperature of their storage. It allows the calculation of the rate of reaction and the Arrhenius parameters taking into account the composition, stoichiometry and thermochemical characteristics of the reaction, the excess pressure of the gaseous product in the reactor and the physical properties of the reactant (sample size and the density of the reactant). Within the TM, it was possible to solve many of the accumulated problems, including the physical nature of the parameters of the Arrhenius equation, the effect of autocatalysis, the kinetic compensation effect and the Topley–Smith effect. To overcome the lasting crisis in the kinetics of heterogeneous reactions, it is necessary to advance the public discussion of the current situation and search for appropriate ways to replace the activation model by the TM.

Mechanistic Investigations of Uncatalyzed and Ruthenium(III) Catalyzed Oxidation of Vanillin by Periodate in Aqueous Alkaline Medium

The kinetics and mechanism of uncatalyzed and ruthenium(III) catalyzed oxidation of vanillin (Van) by periodate were studied in alkaline medium at 298 K, and at constant ionic strength of 0.3 mol·dm−3. The reaction exhibits 1:1 stoichiometry ([Van]:[periodate]). The reaction shows first-order kinetics in [periodate] and [Ru(III)] and less than unit order with respect to [Van] and [OH−]. The ionic strength and dielectric constant of the medium did not affect the rate significantly. The main products were identified by spot tests, melting temperature and FT-IR. From the effect of temperature on the reaction rate, the Arrhenius and activation parameters have been calculated. The catalytic constant (K C) was also calculated for Ru(III) catalysis at different temperatures. Plausible mechanisms have been proposed and rate laws explaining the experimental results are derived. Kinetic studies suggest that the active species of periodate and Ru(III) were [H2IO6]3− and [Ru(H2O)5OH]2+, respectively. The reaction constants involved in the different steps of the mechanism were calculated. The activation parameters with respect to the slow step of the mechanism, along with the corresponding thermodynamic quantities, were determined and discussed.

Quantitative cooling histories from stranded diffusion profiles

Stranded elemental or isotopic diffusion profiles in geological materials have the potential to reveal information on the thermal history of the host sample. In the specific case of a concentration step that is established at high temperature, the extent of diffusive relaxation during cooling depends on the details of the cooling path and the Arrhenius diffusion law of the species of interest: In principle, a measured profile in a sample can provide quantitative information on the nature of the cooling path if the diffusion law is known. Using a combination of mathematics and numerical simulations, we derive a simple relationship describing the extent of profile relaxation (as gauged by the slope S 0 of a diffusion profile) as a function of the initial temperature (T i) and cooling rate ( $$\dot{T}$$ ) of the system and the activation energy (E a) and pre-exponential factor (D 0) for diffusion: $$\log S_{0} = 2.504 - \frac{1}{2}\log D_{0} - \log T_{\text{i}} + \frac{1}{2}\log E_{\text{a}} + \frac{1}{2}\log \dot{T} + \left( {26.11\frac{{E_{\text{a}} }}{{T_{\text{i}} }}} \right)$$ The initial temperature T i is expressed in K, $$\dot{T}$$ is in °/s, D 0 is in m2/s, and E a is in kJ/mol. The slope of the profile of interest can be estimated either at the midpoint of an interdiffusion profile or at a crystal margin. In the former case, concentrations are normalized to a difference of 100 between the upper (=100) and lower (=0) initial concentration plateaus. For profiles at crystal margins, the normalization range is 0 to 50. The equation above applies equally well to linear and exponential cooling paths because the extent of relaxation indicated by S 0 is essentially the same for a given linear cooling path and an exponential one characterized by the same initial cooling rate. Cooling from the top of parabolic T–t “dome” results in more extensive profile relaxation; this is also well described by the above equation if the leading constant 2.504 is changed to 2.165. If S 0 of a stranded profile has been characterized in the laboratory, and if the Arrhenius law of the diffusant is known, the above equation can be solved uniquely for one of the cooling path parameters (T i or $$\dot{T}$$ ) if the other—which will usually be T i—is constrained by phase equilibria or the geological context of the sample. Alternatively, if a sample exhibits stranded profiles for two diffusants having different E a and D 0 values, two versions of the above equation can be solved simultaneously for both the initial temperature and the cooling rate. The equation above can be implemented for purposes other than estimating T–t histories: e.g., assessing whether an observed concentration profile is truly the result of diffusion or a consequence of changing phase composition during growth. Our approach also raises the possibility not only of cross-checking multiple laboratory-based diffusion laws but also of estimating Arrhenius parameters for uncharacterized diffusants.

Size Resolved High Temperature Oxidation Kinetics of Nano-Sized Titanium and Zirconium Particles.

While ultrafine metal particles offer the possibility of very high energy density fuels, there is considerable uncertainty in the mechanism by which metal nanoparticles burn, and few studies that have examined the size dependence to their kinetics at the nanoscale. In this work we quantify the size dependence to the burning rate of titanium and zirconium nanoparticles. Nanoparticles in the range of 20-150 nm were produced via pulsed laser ablation, and then in-flight size-selected using differential electrical mobility. The size-selected oxide free metal particles were directly injected into the post flame region of a laminar flame to create a high temperature (1700-2500 K) oxidizing environment. The reaction was monitored using high-speed videography by tracking the emission from individual nanoparticles. We find that sintering occurs prior to significant reaction, and that once sintering is accounted for, the rate of combustion follows a near nearly (diameter)(1) power-law dependence. Additionally, Arrhenius parameters for the combustion of these nanoparticles were evaluated by measuring the burn times at different ambient temperatures. The optical emission from combustion was also used to model the oxidation process, which we find can be reasonably described with a kinetically controlled shrinking core model.

An advanced reaction model determination methodology in solid-state kinetics based on Arrhenius parameters variation

Overlapping of parallel or consecutive reac- tions caused to variation of activation energy and pre-ex- ponential factor and deconvolution of simultaneous reactions rather than fitting the experimental curve by assuming variable kinetic parameters could supply a deeper conception into the mechanism(s) of reaction. The well- known reaction model determination methods are based on the choice of constant Arrhenius parameters and the use of approximations. To solve this limitation, an advanced method of reaction mechanism model determination based on the Arrhenius parameters variation was proposed. This method appears to accurately simulate single step as well as multi-step reactions kinetics. The proposed method was experimentally verified by taking an experimental example of non-isothermal desulfurization kinetics of CuOCuSO4 in the nanoscale range. Then, the physical meaning of models was effectively interpreted.

The kinetics of carbon dioxide and propylene oxide copolymerization catalyzed by binary catalyst system

The kinetics of carbon dioxide and propylene oxide copolymerization was investigated in order to obtain Arrhenius parameters for the reaction in the presence of the efficient binary catalytic system (salen)Co(DNP)/[PPN]Cl. The reaction rate was followed by measuring the uptake of carbon dioxide during copolymerization. The steady-state rate of the reaction reaches a maximum value at carbon dioxide pressure of 0.6–0.7 MPa. At the reaction conditions, the dependences of the reaction rate on the concentrations of reagents follow the first-order kinetic low. The value of effective activation energy is equal to 45.7 ± 2.0 kJ/mol, and pre-exponential factor in the Arrhenius equation is equal to (5.1 ± 0.1) × 105 L2/(mol2 s). The poly(propylene carbonate) produced was shown to be a regio-regular copolymer with a bimodal molecular weight distribution.

Durability Testing of Parabolic Trough Receivers – Overheating, Thermal Cycling, bellow Fatigue and Antireflex-Coating Abrasion

Abstract This paper describes accelerated aging tests on parabolic trough receivers. Overheating of parabolic trough receivers about 80-100 K over the nominal operating temperature is applied for accelerated aging of the absorber coating.A lifetime prediction based on the Arrhenius parameters requires extensive testing; A reduced test with heating receivers to 478 °C for 1000 hours is applied on receivers for oil fluid in order to compare heat loss and optical efficiency before and after such accelerated aging. In a further test set, such receivers are thermally cycled between 200 °C and 478 °C for 100 times. A bellow fatigue test has been developed for testing of the bellows stability for the compression and expansion. Receivers are subjected to 20,000 cycles and rested for a 24 hour waiting period. The receiver heat loss during the bellow fatigue test shall not increase more than 30%. Durability of the antireflex coating on the glass is tested with the Taber linear abrasor using the CS-10F rubber (¾”) and MIL 12397 Eraser (¼”). Both abrasive materials proved to be suited to obtain reproducible results, although the discussion is still ongoing on which material should be used. The larger diameter of the CS-10F rubber offers the advantage that transmittance measurement with the Lambda 950/1050 spectrophotometer can be performed without the necessity for multiple abrading stripes.

Experimental and Computational Studies of the Kinetics of the Reaction of Atomic Hydrogen with Methanethiol.

The overall rate constant for H + CH3SH has been studied over 296-1007 K in an Ar bath gas using the laser flash photolysis method at 193 nm. H atoms were generated from CH3SH and in some cases NH3. They were detected via time-resolved resonance fluorescence. The results are summarized as k = (3.45 ± 0.19) × 10(-11) cm(3) molecule(-1) s(-1) exp(-6.92 ± 0.16 kJ mol(-1)/RT) where the errors in the Arrhenius parameters are the statistical uncertainties at the 2σ level. Overall error limits of ±9% for k are proposed. In the overlapping temperature range there is very good agreement with the resonance fluorescence measurements of Wine et al. Ab initio data and transition state theory yield moderate accord with the total rate constant, but not with prior mass spectrometry measurements of the main product channels leading to CH3S + H2 and CH3 + H2S by Amano et al.

Pyrolysis of carbazole: Experimental results and kinetic study

Contents and types of organic nitrogen compounds (ONCs) in crude oil can critically affect the quality and the economic viability of oil products. In this article, anhydrous thermal cracking of carbazole was carried out using an autoclave at 425–525°C, and heating times ranging from 187.5 to 237.5h. The pyrolysis products were qualitatively and quantitatively characterized by gas chromatograph- thermal conductivity detector-flame ionization detector, gas chromatography–mass spectrometry and elemental analyzer. Reaction mechanism and kinetics were investigated on the basis of the experimental data. The results show that primary reaction products are aromatic hydrocarbons, N-containing compounds as well as CH4 and H2; whereas NH3, HCN and C2H6 are minor products. At elevated temperatures degradation of carbazole undergoes simultaneously decomposition and condensation, involving cracking of CN bonds and CC bonds and forming of polycarbazole.Carbazole pyrolysis was demonstrated 0.8-order, and associated Arrhenius parameters of [E (KJ/mol), A (s−1)]=[321.628, 1.832×1017] were determined. In comparison with dibenzothiophene, thermal stability of carbazole seems to be more unstable during thermal processing of residual oil. The present study may further improve our understanding of the evolution of complex ONCs in heavy oil refining.

Water concentration distribution in coatings during accelerated weathering protocols

The long outdoor service life of painted metal and wood objects, often measured in decades, requires the use of accelerated weathering protocols to predict the long-term efficacy and performance of new barrier protective coating candidates. The mechanism of damage imposed on a coating system in accelerated weathering tests must have parity with the damage mechanisms occurring within the system as it undergoes natural, in-service weathering. Similarly, the physical conditions involved in the accelerated exposure regime, including water distribution as it is defined both temporally and spatially, must show equivalency to the natural exposure regime. An added complication in accurately accelerating coating damage is that the wet and dry cycles of accelerated weathering and corrosion test protocols are often performed at different and elevated temperatures from in-service exposure, which results in altered bulk transport and diffusion rates of water during each phase of the weathering or corrosion protocol, when compared to those rates experienced in field or in-service conditions. In this study, Fick’s law of diffusion is applied to coating surfaces exposed to surface water concentrations at cyclical intervals for a set of two-stage accelerated weathering protocols. The governing equations are solved using Laplace transforms followed by time rescaling to account for the variation in temperature, which impacts the diffusion coefficient between the wet and dry portions of several accelerated weathering protocols. This serves to predict the asymptotic average water concentration within the coating as well as at the coating–metal interface, based on the diffusion and temperature parameters of the coating and the parameters of the accelerated weathering protocol, including the duration of each imposed wet or dry stage. The analytic solution to Fick’s second law also allows the water concentration at the substrate–coating interface to be predicted based on Arrhenius parameters of the diffusion process. This resultant average time of wetness and water concentration variance at the coating–substrate interface can be used to more directly compare corrosion and adhesion loss between various accelerated weathering protocols and natural weathering conditions. The numerical average and range of water concentration as a function of coating depth can then be used to interpret coating damage distribution with depth, and enable more insightful comparison of the results of various accelerated weathering protocols. The simulations indicate that good barrier systems may actually exhibit increased barrier properties in accelerated protocols as compared to systems with mediocre or poor barrier performance as determined by global diffusion coefficients. The good barrier coating imparts substantially less exposure challenge to the interface than the mediocre or poor barrier coatings in accelerated weathering protocols. Therefore, in industry-standard tests, the observed performance gain of good barrier coating systems over poor systems may be unduly exaggerated. However, the overall exposure challenge to the interface of a good barrier coating is likely to be larger in service or field conditions due to the much extended time of wet exposure. Thus, laboratory-accelerated weathering cycles that do not consider the impact of temporal and spatial diffusion could potentially misrepresent the quality of a coating, in most cases overestimating the performance of coatings with good baseline barrier protection for adhesion or corrosion protection. In other words, the accelerated weathering protocols do not equally challenge the interface of different coatings operating in the same in-service conditions.

Thiol–Disulfide Exchange in Peptides Derived from Human Growth Hormone During Lyophilization and Storage in the Solid State

Lyophilization (freeze-drying) is frequently used to stabilize protein therapeutics. However, covalent modifications such as thiol-disulfide exchange and disulfide scrambling can occur even in the solid state. The effects of lyophilization and storage of lyophilized powders on the mechanism and kinetics of thiol-disulfide exchange have not been elucidated and are explored here. Reaction kinetics was monitored in peptides corresponding to tryptic fragments of human growth hormone (T20 + T20-T21 or T20 + cT20-T21) during different stages of lyophilization and during storage of the lyophilized powders at 22°C and ambient RH. The concentrations of reactants and products were determined using RP-HPLC and product identity confirmed using liquid chromatography-mass spectrometry. Loss of native disulfide was observed for the reaction of T20 with both linear (T20-T21) and cyclic (cT20-T21) peptides during the primary drying step; however, the native disulfides were regenerated during secondary drying with no further change till the end of lyophilization. Deviations from Arrhenius parameters predicted from solution studies and the absence of buffer effects during lyophilization suggest that factors such as temperature, initial peptide concentration, buffer type, and concentration do not influence thiol-disulfide exchange during lyophilization. Results from a "cold finger" method used to study peptide adsorption to ice indicate that there is no preferential adsorption to the ice surface and that its presence may not influence disulfide reactivity during primary drying. Overall, reaction rates and product distribution differ for the reaction of T20 with T20-T21 or cT20-T21 in the solid state and aqueous solution, whereas the mechanism of thiol-disulfide remains unchanged. Increased reactivity of the cyclic peptide in the solid state suggests that peptide cyclization does not offer protection against lyophilization and that damage induced by a process stress further affects storage stability at 22°C and ambient RH.