Synthesis of Hydroxy and Methoxy Perylene Quinones, Their Spectroscopic and Computational Characterization, and Their Antiviral Activity^¶

Abstract

Hydroxy and methoxy perylene quinones are synthesized in an attempt to isolate the essential spectroscopic and biological features of light‐induced antiviral agents such as hypericin and hypocrellin. Unlike their naturally occurring counterparts, these synthetic quinones bear the carbonyl, hydroxyl, and methoxy groups in the “bay region.” The hydroxy and methoxy compounds have rich absorption spectra with broad features in the visible (∼450–800 nm) and relatively more intense and narrow features at wavelengths ≤350 nm. High‐level ab initio quantum mechanical calculations assign the features in the absorption spectra to electronic transitions from So to S2 and to higher‐lying electronic states. The calculations indicate that in the ground state the trans dihydroxy isomer is 12.5 kcal/mol lower in energy than the cis dihydroxy isomer and is thus the only species present. The lowest‐energy trans methoxy ground state isomer and the lowest‐energy cis methoxy ground state isomer are found to be degenerate. An additional cis methoxy isomer 6.3 kcal/mol higher in energy than the global minimum is assumed to contribute to the spectrum and is also considered. Finally, the synthetic compounds exhibit similar light‐induced antiviral activity to each other, but significantly less than that of hypericin.

Positive Reinforcement for Viruses

“…However, a few differences can be noted. As opposed to the simple benzene group in the hydrophobic tail of LJ001, the hydrophobic group, perylene, present in effective RAFIs has a structure closely related to hypocrellin A, a well-known photosensitizer with antiviral and antineoplastic activities belonging to the family of quinones (Krishnamoorthy, et al , 2005). Hydrophobic photosensitizers (such as hypocrellin A) insert into membranes and upon photoactivation (activation by light) produce reactive oxygen species (ROS) that may be damaging to membrane components.…”

Synthesis and studies of bay‐substituted perylene diimide‐based D–A–D‐type SM acceptors for OSC and antimicrobial applications

“…In the literature, it is reported that some of PDI derivatives possess antibacterial [22], antifungal [23], and anticancer activities [24]. Naturally obtained PDI derivatives such as hypericin and its derivatives have shown inhibitory activity against bacteria [25]. The fast growing microbial resistance to the conventional anti‐infectious agents has necessitated the continuing search for new classes of compounds with novel methods of antimicrobial activity.…”