Andreas Kornherr

Is the rate constant of chain propagation kp in radical polymerization really chain-length independent ?

A careful investigation of the k p data obtained from pulsed-laser polymerization at different pulse separations to in a lot of systems has revealed that k p exhibits a slight but significant decrease when t 0 is increased, corresponding to an about 20% decrease of k p extending over several hundreds in degree of polymerization. Transformation of this integral effect to individual chain-lengths reduces this range, of course, but still shows more than one hundred propagation steps to be concerned. This is interpreted in terms of a decrease of the monomer concentration at the site of propagation caused by the segments already added to the growing chain.

Molecular dynamics simulations of the adsorption of industrial relevant silane molecules at a zinc oxide surface

The physical behavior of different adsorbed silane molecules (octyltrihydroxysilane, aminopropyltrihydroxysilane, and thiolpropyltrihydroxysilane) at a ZnO surface (0001) dissolved in isopropanol are studied via constant temperature (298 K) molecular dynamics simulations. The adsorbed silane molecules exhibit a different behavior depending on the chemical nature of their tail. Octyltrihydroxysilane molecules with their rather unpolar tail show two distinct, energetic different orientations at the polar metal oxide surface. Mostly the three polar hydroxy groups of the head are in contact with ZnO the unpolar tail remaining in the isopropanol phase. Occasionally only two hydroxy groups interact with the surface the whole tail simultaneously being attached. On the contrary, due to their highly polar tail aminopropyltrihydroxysilane molecules have only one favorite orientation at the surface: Apart from some minor fluctuations two hydroxy groups as well as the amino group of the tail are in contact with the ...

Chain‐length dependent termination in pulsed‐laser polymerization, 7. The evaluation of the power‐law exponent b from the chain‐length distribution in the low frequency (single‐pulse) limit for the reference systems styrene and methyl methacrylate in bulk at 25°C

The chain-length distribution (CLD) was examined for polymers prepared by low frequency pulsed laser polymerization (LF-PLP), i.e. for very long pulse separations in the so-called low frequency or single pulse limit. The data were fitted to the theoretical CLD which could be derived in a closed form for a chain-length dependent rate coefficient k t and the parameter b that characterizes this chain-length dependence was determined by this fitting procedure, b values close to 0.2 were obtained for styrene as well as for MMA, indicating a moderate chain-length dependence of k t at low conversions. This result, which is in good agreement with data evaluated by other methods in our laboratory, points to the fact that under these conditions end-segment diffusion is the rate-determining step in bimolecular termination. Factors like moderate chain transfer to monomer and uncertainties with respect to the mechanism of termination (combination or disproportionation) appear to have very little influence on this result.

Molecular dynamics simulations for drug dosage form development: thermal and solubility characteristics for hot-melt extrusion

Properties of pharmaceutical drug polymer mixtures like miscibility, stability and drug release are determined by the interactions of active pharmaceutical ingredients (APIs) and excipients (e.g. plasticisers) with functional polymers. Molecular dynamics (MD) simulations (Materials Studio®, COMPASS force field) are used to predict the principal behaviour of such drug products, especially miscibility and glass transition temperature (T g). Different mixtures containing APIs (theophylline or ibuprofen (IBU)) and water-soluble (triethyl citrate, (TEC)) or water-insoluble plasticiser (acetyl tributyl citrate (ATBC) or dibutyl sebacate (DBS)) dissolved/dispersed in a cationic polymethacrylate (EUDRAGIT® RS) were studied. Force field-based calculations of the cohesive energy densities of single constituents led to a qualitative approach according to Hanson describing the solid state of the mixture, while further calculations on the basis of the theory of free energy of mixing facilitated a semi-quantitative prediction. In the case of miscibility also calculation of T g was possible via modelling specific volumes of amorphous cells at various temperatures. The simulated data correlated well with the experimental data obtained from differential scanning calorimetry (DSC) of drug products processed via hot-melt extrusion. Accordingly, the described method facilitates a good estimate of pharmaceutical polymer drug mixtures, thus decreasing product development time, as well as the consumption of active ingredients.

Chain‐length dependent termination in pulsed‐laser polymerization, 4. The influence of the type of mean involved in the bimolecular termination step

The chain-length distribution (cld) of living and dead chains and their moments have been calculated by an iterative simulation procedure for pseudostationary laser-induced polymerization (without chain-transfer) assuming various types of means between the lengths of the two chains involved in the termination process. The overall appearance of the cld is dramatically influenced by the type of mean: the stronger the influence of the shorter of the two chains the more prominent are the extra-peaks of the cld and the smaller the rate of polymerization. The different types of means are subject to different short-chain effects; in the long-chain limit, however, the correct exponent of the power law governing the chain-length dependence of k t is correctly recovered in all cases. The estimation of k t (1,1) works the better the less prominent is the role of the smaller chain. Because of its close proximity to the diffusion mean the geometric mean approximation - although unphysical - is proved to give an excellent qualitative and quantitative description of all effects associated with chain-length dependent termination.

Atomistic molecular-dynamics simulations of the size and shape of polyethylene in hexane at infinite dilution

Parameters characteristic of size and shape of single polyethylene chains consisting of 15-60 monomer units dissolved in hexane are calculated by use of molecular-dynamics simulations based on a fully atomistic representation of the system. Results are compared with corresponding calculations in vacuum as well as Monte Carlo simulations of coarse-grained chains. The major concern of the study is a careful check of actual limits and possibilities of atomistic simulations of global properties of polymers. As expected such simulations are still restricted to rather small chain lengths but are already large enough to obey the characteristics of polymer coils.

The Influence of Chain Length-Dependent Propagation on the Evaluation of the Chain Length Dependence of the Rate Coefficient of Bimolecular Termination, 1. PLP–SEC Methods

Chain length distributions have been calculated for polymers prepared by pulsed laser polymerization (PLP) under the condition that not only chain termination but also chain propagation is subject to chain length dependence. The interplay between these two features is analyzed with the chain length dependence of the rate coefficient of termination kt introduced in the form of a power law and that of propagation kp modeled by a Langmuir-type decrease from an initial value for zero chain length to a constant value for infinite chain lengths. The rather complex situation is governed by two important factors: the first is the extent of the decay of radical concentration [R] during one period under pseudostationary conditions, while the second is that termination events are governed by [R]2 while the propagation goes directly with [R]. As a consequence there is no general recommendation possible as to which experimental value of kp is best taken as a substitute for the correct average of kp characterizing a specific experiment. The second point, however, is apparently responsible for the pleasant effect that the methods used so far for the determination of kt and its chain length dependence (i.e., plotting some average of kt versus the mean chain-length of terminating radicals on a double-logarithmic scale) are only subtly wrong with regard to a realistic chain length dependence. This is especially so for the quantity kt* (the average rate coefficient of termination derived from the rate of polymerization in a PLP system) and its chain length dependence.

Lactonisation--a degradation pathway for active pharmaceutical compounds: an in silico study in amorphous trehalose.

The lactonisation of a CCR1 inhibitor (CC chemokine receptor 1, involved in autoimmune diseases) featuring a hydroxyl group in a gamma-position (gamma-OH) with respect to an amide group has been investigated in silico. The two key steps of the lactonisation reaction are (i) rearrangement to an optimal conformation and (ii) the formation of the lactone (ring closure) and expulsion of NH3. Quantum chemical calculations in the gas phase were employed to identify conformers of the molecule with favorable starting geometries for a lactonisation reaction. In total, calculations of 1296 conformers revealed that it is energetically feasible for an inhibitor molecule to adopt a conformation where the carbon atom of the amide group (C(amide)) is suitably close to the oxygen atom of the gamma-OH (O(gamma)) to facilitate a successful lactonisation reaction. Additionally, molecular dynamics methods were used to show that rearrangement to a suitable conformer for lactonisation to occur happens to a lesser extent when the CCR1 inhibitor was embedded in an amorphous trehalose matrix (a model carbohydrate excipient). The mechanism of the actual lactonisation was investigated using the complete Linear Synchronous Transit/Quadratic Synchronous Transit (LST/QST) method. This was performed in both the gas phase and in water and was found to be a concerted reaction.

On the (im)possibility of evaluating correct individual rate constants of chain propagation kp and chain termination kt by combining kp2/kt and kp/kt data for chain-length dependent termination

Feature Article; On the basis of simulated data two ways of evaluating individual rate constants by combining k 2 p /k t and k p /k t (k p , k t = rate constants of chain propagation and termination, respectively) were checked considering the chain-length dependence of k t . The first way tried to make use of the fact that pseudostationary polymerization yields data for k 2 p /k t as well as for k p /k t referring to the very same experiment, in the second way k 2 p /k t (from steady state experiments) and k p /k t data referring to the same mean length of the terminating radical chains were compared. In the first case no meaningful data at all could be obtained because different averages of k t are operative in the expressions for k p /k t and k 2 p /k t . In spite of the comparatively small difference between these two averages (15% only) this makes the method collapse. The way, which can be regarded as an intelligent modification of the classical method of determining individual rate constants, at least succeeded in reproducing the correct order of magnitude of the individual rate constants. However, although stationary and pseudostationary experiments independently could be shown to return the same k t for the same average chain-length of terminating radicals within extremely narrow limits no reasonable chain-length dependence of k t could be derived in this way. The reason is an extreme sensitivity of the pair of equations for k p /k t and k 2 p /k t towards small errors and inconsistencies which renders the method unsuccessful even for the high quality simulation data and most probably makes it even collapse for real data. This casts a characteristic light on the unsatisfactory situation with respect to individual rate constants determined in the classical way, regardless of a chain-length dependence of termination. As a consequence, all efforts of establishing the chain-length dependence of k t are recommended to avoid this way and should rather resort to methods based on inserting a directly determined k p into the equations characteristic of k 2 p /k t or k p /k t , properly considering the chain-length dependent character of k t . character of k t .

Chain‐length dependent termination in rotating sector polymerization, 1. The evaluation of the rate constant of chain propagation kp

The chain-length distributions (CLDs) of polymers prepared by rotating-sector (RS) techniques under pseudostationary conditions were simulated for the case of chain-length dependent termination and analysed for their suitability of determining the rate constant of chain propagation kp from the positions of their points of inflection. The tendency to underestimate k p is a little more pronounced than in pulsed-laser polymerization (PLP) but, interestingly, the situation improves in the presence of chain-length dependent termination. The estimates also were found to be more precise a) for smaller rates of initiation, b) for higher order points of inflection, c) if termination is by combination, d) if the role played by the shorter one of the two chains becomes less dominant. Taken in all, the determination of k p from the points of inflection in the CLD of RS-prepared polymers may well compete with the more famous PLP method, especially if some care is taken with respect to the choice of experimental conditions.