Dual Functioning Thieno‐Pyrrole Fused BODIPY Dyes for NIR Optical Imaging and Photodynamic Therapy: Singlet Oxygen Generation without Heavy Halogen Atom Assistance

Abstract

We discovered a rare phenomenon wherein a thieno-pyrrole fused BODIPY dye (SBDPiR690) generates singlet oxygen without heavy halogen atom substituents. SBDPiR690 generates both singlet oxygen and fluorescence. To our knowledge, this is the first example of such a finding. To establish a structure-photophysical property relationship, we prepared SBDPiR analogs with electron-withdrawing groups at the para-position of the phenyl groups. The electron-withdrawing groups increased the HOMO-LUMO energy gap and singlet oxygen generation. Among the analogs, SBDPiR688, a CF3 analog, had an excellent dual functionality of brightness (82290 m(-1) cm(-1) ) and phototoxic power (99170 m(-1) cm(-1) ) comparable to those of Pc 4, due to a high extinction coefficient (211 000 m(-1) cm(-1) ) and balanced decay (Φflu =0.39 and ΦΔ =0.47). The dual functionality of the lead compound SBDPiR690 was successfully applied to preclinical optical imaging and for PDT to effectively control a subcutaneous tumor.

Alkane Chain‐extended Pterin Through a Pendent Carboxylic Acid Acts as Triple Functioning Fluorophore, 1O2 Sensitizer and Membrane Binder

“…Over the past 6-8 years, "smart" compounds that possess dual fluorescence sensing and singlet oxygen sensitizing properties have become a hot topic (14)(15)(16), with success reported in dual function image-guided and photodynamic therapy applications (PDT) (17)(18)(19)(20)(21)(22)(23)(24)(25). Indeed, our previous Oand N-decyl-pterins possessed good singlet oxygen quantum yields (Φ Δ ), but had poor fluorescence quantum yields (Φ F ) some 4-30 fold less compared to native pterin, thereby fulfilling only two of three facets, even though a minor fluorescence increase was observed when intercalated in the membrane (10).…”

Photoinduced Electron Transfer‐based Halogen‐free Photosensitizers: Covalent meso‐Aryl (Phenyl, Naphthyl, Anthryl, and Pyrenyl) as Electron Donors to Effectively Induce the Formation of the Excited Triplet State and Singlet Oxygen for BODIPY Compounds

“…Unsubstituted BODIPY, for example, shows fluorescence efficiency near unity (0.97±0.03) and a long fluorescence lifetime of 6.89 ns in methanol, which leaves it little space to form the T 1 state. The heavy atom effect with iodine or bromine substitution and dimerization are often used to make BODIPY efficient in T 1 formation . By covalently linking an aryl as an electron‐donor unit (benzene, naphthalene, anthracene, or pyrene) onto the meso position of the BDP (Scheme ), we could make BODIPY compounds generate the T 1 state and hence singlet oxygen efficiently.…”

“…The heavy atom effect with iodine or bromine substitution and dimerization are often used to make BODIPYefficient in T 1 formation. [21,22] By covalently linking an aryl as an electron-donor unit (benzene, naphthalene, anthracene, or pyrene) onto the meso position of the BDP (Scheme 1), we could make BODIPY compounds generate the T 1 state and hence singletoxygen efficiently.T hisa ryl substitution methode xtends our previous dimerization and bromination techniques to make BODIPY generate T 1 and singlet oxygen effectively.Moreover,t he capability is sensitive to external conditions that make them good activatible PSs.…”

Directly Connected AzaBODIPY–BODIPY Dyad: Synthesis, Crystal Structure, and Ground- and Excited-State Interactions

“…In recent past, BF 2 -chelated dipyrromethenes (BODIPYs) [1][2][3][4][5] have drawn major attention because of their broader range of applications as laser dyes, 6-8 fluorescent stains and labels in imaging, [9][10][11][12] indicator dyes in sensors and chemosensors, [13][14][15] photodynamic therapy (PDT) agents, [16][17][18][19] and building light energy converting donor-acceptor systems. [20][21][22][23][24][25][26][27][28] The tremendous potential applications of BODIPY dyes is attributable to their attractive photophysical properties such as narrow absorption and emission bands, high molar absorption coefficients and quantum yields, high solubility in different organic solvents, and low sensitivity to solvent polarity.…”