Metabolite-based model predictive control of cell growth

Batch-to-batch variation causes significant challenges in the production of cell and gene therapies in terms of manufacturing planning and process comparability. Since the processes deal with living systems that are complex and time-varying, remediating process variability requires dynamic control over the Critical Process Parameters. Please click Additional Files below to see the full abstract

Density Functional Theory Study on the Aggregation and Dissociation Behavior of Lithium Chloride in THF and Its Interaction with the Active Centers of the Anionic Polymerization of Methyl Methacrylate and Styrene

ABSTRACT: The structure of LiCl in tetrahydrofuran (THF) solution and its effect on the structure and stability of active sites of the anionic polymerization of methyl methacrylate (MMA) and styrene (St) was studied using the quantum-chemical density functional theory (DFT) approach. In the case of MMA anionic polymerization, it was found that LiCl forms stable mixed aggregates with ester enolates which model the PMMA living chain ends, thus preventing them from self-aggregation. They may even stabilize more reactive zwitterionic structures of these chain ends. The dissociation of solvated LiCl dimers to form Li + (THF)4 cations is slightly endothermic in THF, while scavenging of Li + (THF)4 by LiCl dimers to produce more stable quintuple cations [(THF)3Li-Cl-Li(THF)2-Cl-Li(THF)3] + is even exothermic. Therefore, if the concentration of LiCl exceeds a certain threshold value, Li + (THF)4 cations should effectively be scavenged by LiCl dimers. Thus, increasing LiCl concentration below the threshold concentration should lead to an increase in the concentration of free Li + (THF)4 cations. In the anionic polymerization of styrene in the presence of LiCl this results in the suppression of PSt-Li chain end dissociation due to the common ion effect, slowing down the polymerization. Further addition of LiCl above the threshold concentration should decrease the concentration of free Li + (THF)4 cations, leading to enhanced PSt-Li chain end dissociation, thus increasing the polymerization rate, in agreement with kinetic data reported in the literature

The Mechanism of the Propagation in the Anionic Polymerization of Polystyryllithium in Non-Polar Solvents Elucidated by Density Functional Theory Calculations. A Study of the Negligible Part Played by Dimeric Ion-Pairs under Usual Polymerization Conditions

The elementary processes occurring in the anionic polymerization of styrene with dimerically associated polystyryllithium (propagation during the anionic polymerization of dimeric polystyryllithium) in the gas phase and cyclohexane were studied using MX062X/6-31+G(d), a recently developed density functional theory (DFT) method and compared with the polymerization of styrene with non-associated polystyryllithium, which was described in a previous study. The most stable transition state in the reaction of styrene with dimeric polystyryllithium has a structure in which the side chains of styrene and the two chain end units of polystyryllithium are located in the same direction around the Li atom near the reactive site. The relative enthalpy for this transition state in cyclohexane is 28 kJ·mol−1, which is much lower than that for the reaction of non-associated polystyryllithium (51 kJ·mol−1). However, the relative free energy (which determines the rate constant) for the former is 93 kJ·mol−1, which is greater than that for the latter by 7 kJ·mol−1, indicating that the latter reaction (reaction with non-associated polystyryllithium) is advantageous over the former (reaction with dimeric polystyrylllithium). Their rates of reaction are also affected by initiator concentrations; in the case of reactions with low initiator concentrations, from which high molecular weight polymers are usually obtained, the rate of reaction corresponding to non-associated polystyryllithium is much larger than that corresponding to dimeric polystyryllithium

New Vistas on the Anionic Polymerization of Styrene in Non-Polar Solvents by Means of Density Functional Theory

The elementary processes of anionic styrene polymerization in the gas phase and in cyclohexane were studied using M062X (a recently developed density functional theory (DFT) method) combined with the 6-31+G(d) basis sets, in order to clarify the complicated phenomena caused by the association of the active chain-ends and elucidate the details of the polymerization mechanism. Three types of HSt₂Li (a model structure of polystyryllithium chain-ends) were obtained; the well-known first structure in which Li is coordinated to the side chain, the second structure in which Li is coordinated to the phenyl ring, (both without the penultimate unit coordination), and the third structure in which Li is coordinated to both the chain-end unit and the penultimate styrene unit. Although the third HSt₂Li is the most stable as expected, the free energy for the transition state of its reaction with styrene is higher than those for the other two transition states due to its steric hindrance. The free energy for the transition state of the reaction of the second HSt₂Li with styrene is the lowest, suggesting that the route through it is the predominant reaction path. The penultimate unit effect, slower addition of styrene to HSt₂Li than to HStLi, is attributed to coordination of the penultimate styrene units of the polystyryllithium dimer (one of the starting materials) to its Li atoms. The calculated enthalpy for the reaction barrier of the second HSt₂Li with styrene in cyclohexane was found to agree with the observed apparent activation energy in benzene.status: publishe

Synthesis of new polyisocyanates

New isocyanates with functional groups, e.g. halogen and methyl ester, were polymerized. By means of a transesterification reaction with alcohol chromophores, the methyl ester polyisocyanates were transformed into chromophore functionalized. polymers. In this way, polyisocyanates with a degree of functionalization up to 30% could be obtained. (C) 2001 Elsevier Science B.V. All rights reserved.status: publishe