Formation and characterization of charge transfer complex between alectinib and 2,3-dichloro-5,6-dicyano-1,4-benzoquinone: Application to development of microwell spectrophotometric method

Abstract

Alectinib (ALC) is a novel highly selective anaplastic lymphoma kinase (ALK) inhibitor that is effective in the treatment of patients with advanced ALK-positive non-small cell lung cancer and lymphomas. This study, describes, for the first time, the formation of a charge transfer complex (CTC) between ALC with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ). The CTC was characterized using different spectrophotometric and computational techniques. UV–visible spectrophotometry ascertained the formation of the CTC in methanol via the formation of a new broad absorption band with a maximum absorption peak (λmax) at 505 nm. The molar absorptivity (ε) of the complex was 2.72 × 103 L mol−1 cm−1 and its band gap energy was 1.94 eV. The stoichiometric ratio of ALC:DDQ was found to be 1:1. The association constant of the complex was 9.6 × 102 L mol−1, and its standard free energy was −16.98 J mol−1. Computational calculations were conducted using different calculation tools. The computed geometrical parameters, specifically bond lengths, exhibited variations in the CTC compared to the individual reactants (ALC and DDQ). The Mulliken atomic charge analysis indicated increased values for DDQ (the acceptor) and decreased values for ALC (the donor) in the CTC, confirming the formation of a CTC. The reaction was employed as a basis for a novel microwell spectrophotometric method for the quantification of ALC in its bulk form, capsule content, and uniformity testing. This greenness and high throughput of the method was documented. The method represents a valuable tool for routine use in quality control laboratories for analysis of ALC's bulk form and capsules.