Late-stage modification of drug molecules is a fast method to introduce diversity into the already biologically active scaffold. A notable number of analogs of mefloquine, chloroquine, and hydroxychloroquine have been synthesized, starting from the readily available active pharmaceutical ingredient (API). In the current review, all the modifications sites and reactivity types are summarized and provide insight into the chemistry of these molecules. The approaches include the introduction of simple groups and functionalities. Coupling to other drugs, polymers, or carriers afforded hybrid compounds or conjugates with either easily hydrolyzable or more chemically inert bonds. The utility of some of the compounds was tested in antiprotozoal, antibacterial, and antiproliferative assays, as well as in enantiodifferentiation experiments.

Aminyl tetraradicals with planar tetraazanonacene backbones have quintet (S = 2) ground states and do not show any detectable thermal population of the low-spin excited states up to the highest temperature investigated (100 K) in the 2-methyltetrahydrofuran (2-MeTHF) matrix. This indicates that the nearest electronic excited state (triplet) is at least ∼0.3 kcal mol^–1 higher in energy, that is, the triplet–quintet energy gap, ΔE_TQ > 0.3 kcal mol^–1, which is consistent with the broken-symmetry-DFT-computed ΔE_TQ of about 5 kcal mol^–1. In concentrated (ca. 1–10 mM) solutions of tetraradical 4 in 2-MeTHF at 133 K, a fraction of tetraradicals form a dimer (association constant, K_assoc ≈ 60 M^–1), with a weak, antiferromagnetic exchange coupling, J/k ≈ −0.1 K ∼ 0.2 cal mol^–1, between the S = 2 tetraradicals. This weak intradimer exchange coupling is expected for two tetraradicals at the distance of about 6 Å. The most sterically shielded tetraradical 5 in 2-MeTHF has a half-life of 1 h at room temperature; the product of its decay is the corresponding tetraamine, suggesting that the hydrogen atom abstraction from the solvent is primarily responsible for the decomposition of the tetraradical.