Polymerization Rate Control in <scp>ATRP</scp> : Experimental Kinetics and Machine Learning Predictions of Initiator Efficiency in Quinol Ester, Phenolic Ester‐Amide, and Diamide‐Based Systems

ABSTRACT The effect of initiator structure and configuration on the initiation and kinetics was determined for a series of amide‐and ester‐linked initiators in copper‐mediated atom transfer radical polymerization. In this study, we adopt a hybrid approach, integrating experimental polymerization data with computational modeling to enhance predictive accuracy and mechanistic understanding. Experimentally, polymerization rates were measured for various initiator‐monomer systems, using different initiators. The influence of molecular structure, steric effects, and electronic properties on R p was systematically analyzed. The lower polymerization rate observed with the amide‐based initiator may be attributed to the coordination of the copper catalyst with the nitrogen of the amide group through the lone pair of electrons on nitrogen. The efficiency of an initiator is attributed to the competing effect of the substituents attached next to the CX (X = halogen) bond. Computationally, we employed Chemical Graph Theory (CGT) descriptors, including Wiener index, Hosoya index, Randic index, Electronegativity index, Flexibility index, and steric hindrance, to correlate molecular structure with polymerization kinetics. A multiple linear regression (MLR) model was initially developed to establish a mathematical relationship between topological indices and experimentally measured polymerization rates. Our findings indicate that Randic index and Electronegativity index significantly influence polymerization rates, while steric hindrance exhibits a strong negative correlation with R p .