Feasibility and performance of cross-clone Raman calibration models in CHO cultivation.

Raman spectroscopy is widely used in monitoring and controlling cell cultivations for biopharmaceutical drug manufacturing. However, its implementation for culture monitoring in the cell line development stage has received little attention. Therefore, the impact of clonal differences, such as productivity and growth, on the prediction accuracy and transferability of Raman calibration models is not yet well described. Raman OPLS models were developed for predicting titer, glucose and lactate using eleven CHO clones from a single cell line. These clones exhibited diverse productivity and growth rates. The calibration models were evaluated for clone-related biases using clone-wise linear regression analysis on cross validated predictions. The results revealed that clonal differences did not affect the prediction of glucose and lactate, but titer models showed a significant clone-related bias, which remained even after applying variable selection methods. The bias was associated with clonal productivity and lead to increased prediction errors when titer models were transferred to cultivations with productivity levels outside the range of their training data. The findings demonstrate the feasibility of Raman-based monitoring of glucose and lactate in cell line development with high accuracy. However, accurate titer prediction requires careful consideration of clonal characteristics during model development.

Enantioselective Synthesis of 1,12-Disubstituted [4]Helicenes.

A highly enantioselective synthesis of 1,12-disubstituted [4]carbohelicenes is reported. The key step for the developed synthetic route is a Au-catalyzed intramolecular alkyne hydroarylation, which is achieved with good to excellent regio- and enantioselectivity by employing TADDOL-derived (TADDOL=α,α,α,α-tetraaryl-1,3-dioxolane-4,5-dimethanol) α-cationic phosphonites as ancillary ligands. Moreover, an appropriate design of the substrate makes the assembly of [4]helicenes of different substitution patterns possible, thus demonstrating the synthetic utility of the method. The absolute stereochemistry of the newly prepared structures was determined by X-ray crystallography and characterization of their photophysical properties is also reported.