Heavy Atom-Free Triplet Photosensitizers: Molecular Structure Design, Photophysical Properties and Application in Photodynamic Therapy

Abstract

Photodynamic therapy (PDT) is a promising method for the treatment of cancer, because of its advantages including a low toxicity, non-drug-resistant character, and targeting capability. From a photochemical aspect, a critical property of triplet photosensitizers (PSs) used for PDT reagents is the intersystem crossing (ISC) efficiency. Conventional PDT reagents are limited to porphyrin compounds. However, these compounds are difficult to prepare, purify, and derivatize. Thus, new molecular structure paradigms are desired to develop novel, efficient, and versatile PDT reagents, especially those contain no heavy atoms, such as Pt or I, etc. Unfortunately, the ISC ability of heavy atom-free organic compounds is usually elusive, and it is difficult to predict the ISC capability of these compounds and design novel heavy atom-free PDT reagents. Herein, from a photophysical perspective, we summarize the recent developments of heavy atom-free triplet PSs, including methods based on radical-enhanced ISC (REISC, facilitated by electron spin–spin interaction), twisted π-conjugation system-induced ISC, the use of fullerene C60 as an electron spin converter in antenna-C60 dyads, energetically matched S1/Tn states-enhanced ISC, etc. The application of these compounds in PDT is also briefly introduced. Most of the presented examples are the works of our research group.

Multiple Pathways in the Triplet States Population for a Naphthalenediimide‐C60 Dyad

“…Recently triplet photosensitizers (PSs) have attracted much attention [1,2] for their ability to sensitize long-lived triplet excited states of molecules with intrinsic low triplet yield. [3][4][5][6][7] Due to these properties, triplet PSs have been widely used in photocatalysis, photodynamic therapy (PDT), [1,8,9] photopolymerization, [10] triplet-triplet annihilation upconversion, [11][12][13][14] etc. The role of the triplet PSs played in these applications is usually intermolecular triplet energy transfer (ET) or electron transfer.…”

Sustainable Photooxidation using a Subpart-per-million Heavy-Metal-Free Red-Light Photocatalyst

“…This so-called long-lived “dark excited state” dictates the 1 O 2 quantum yield by maximizing the probability of energy transfer, which is believed to be the key parameter toward highly efficient PSs. The development of new PSs has therefore commonly been achieved by introducing heavy atoms to increase spin–orbit coupling − or torsion angles to populate charge-transfer excited states and maximize intersystem crossing and thereby triplet energy transfer. − Other strategies such as covalent grafting of permanent radicals , or excitonic couplings , have also been discovered but remain less exploited to date.…”

“…The development of new PSs has therefore commonly been achieved by introducing heavy atoms to increase spin−orbit coupling 21−25 or torsion angles to populate charge-transfer excited states and maximize intersystem crossing and thereby triplet energy transfer. 26−30 Other strategies such as covalent grafting of permanent radicals 30,31 or excitonic couplings 32,33 have also been discovered but remain less exploited to date.…”

Fine-tuning of the charge-separated state energy in compact orthogonal naphthalene–phenoxazine dyads and its effect on the thermally-activated delayed fluorescence

“…Among various PSs, heavy-atom-free PSs have the advantages of a low toxicity, low synthesis cost, and long triplet state lifetime. 2,[15][16][17] Traditional triplet PSs invoke the heavy atom effect 3,18 or n-p* 2 p-p* transitions to promote ISC; 19,20 however, they are associated with the limitations of difficult synthesis, short triplet-state lifetimes, 21 limited molecular structures, 15 and so forth. In this regard, triplet PSs based on heavy atom-free molecular structure motifs, such as the spin-orbit charge transfer ISC (SOCT-ISC) mechanism, have attracted much attention owing to their simple molecular structures, feasible derivatization, and efficient ISC.…”