Porpholactone Chemistry: An Emerging Approach to Bioinspired Photosensitizers with Tunable Near-Infrared Photophysical Properties

Abstract

CONSPECTUS: Chlorophylls, known as the key building blocks of natural light-harvesting antennae, are essential to utilize solar energy from visible to near-infrared (NIR) region during the photosynthesis process. The fundamental studies for the relationship between structure and photophysical properties of chlorophylls disclosed the importance of βperipheral modification and thus boosted the fast growth of NIR absorbing/emissive porphyrinoids via altering the extent of π-conjugation and the degree of distortion from the planarity of macrocycle. Despite the tremendous progress made in various porphyrin-based synthetic models, it still remains a challenge to precisely modulate photophysical properties through fine-tuning of β-peripheral structures in the way natural chlorophylls do. With this in mind, we initiated a program and focused on meso-C 6 F 5 -substituted porpholactone (F 20 TPPL), in which one βpyrrolic double bond was replaced by a lactone moiety, as an attractive platform to construct the bioinspired library of NIR porphyrinoids. In this Account, we summarize our recent contributions to the bioinspired design, synthesis, photophysical characterization, and applications of porpholactones and their derivatives. We have developed a general, convenient method to directly prepare porpholactones in large scale up to gram, which forms the chemical basis of porpholactone chemistry. By modulation of the saturation level and in particular regioisomerization of β-dilactone moieties, a synthetic library constituted by a series of porpholactones and their derivatives has been established. Thanks to the electron-withdrawing nature of lactone moiety, derivation of the saturation levels gives help to build stable models for chlorin, bacteriochlorin, and tunichlorin. It is worth noting that regioisomerization of dilactone moieties mimics the relative orientation of β-substituents in natural chlorophylls and hemes, which was considered as the key factor to tune NIR absorption and reactivity. Porpholactones can illustrate the capability of fine-tuning photophysical properties including the excited triplet states by subtle alteration of β-peripheral structures in the presence of transition metals and lanthanides (Ln). Furthermore, they can serve as efficient photosensitizers for singlet oxygen and NIR Ln, showing potential applications in cell imaging and photocytotoxicity studies. The high luminescence, tunable structures, high cellular uptake, and intense NIR absorption render them as promising and competitive candidates for theranostics in vitro and in vivo. Therefore, extending the studies of "porpholactone chemistry" not only tests the fundamental understanding of the structure−function relationship that governs NIR photophysical properties of natural tetrapyrrole cofactors such as chlorophylls but also provides the guiding principles for the bioinspired design of NIR luminescent molecular probes with various applications. Taken together, as a new synthetic porphyrin derivative, porpholactone chemistry shines light on...

Oxazolochlorins 21. Most Efficient Access to meso-Tetraphenyl- and meso-Tetrakis(pentafluorophenyl)porpholactones, and Their Zinc(II) and Platinum(II) Complexes

“…The historically first porpholactone, meso -tetraphenylporpholactone (TPL) was derived from meso -tetraphenylporphyrin (TPP) [ 2 ]. While several phenyl- and substituted phenyl-derivatives were reported [ 3 , 4 ], the by far most popular derivative is the meso -tetrakis(pentafluorophenyl)porpholactone (T F PL) and its metal complexes (T F PLM) [ 1 , 5 , 6 ]. This is because of their relative ease of synthesis in one step from T F PP using a number of different methodologies (see below Scheme 2 ) and the multiple possibilities to derivatize the C 6 F 5 -groups by means of nucleophilic aromatic substitution reactions to, for example, render them water-soluble [ 6 , 7 , 8 ].…”

“…While several phenyl- and substituted phenyl-derivatives were reported [ 3 , 4 ], the by far most popular derivative is the meso -tetrakis(pentafluorophenyl)porpholactone (T F PL) and its metal complexes (T F PLM) [ 1 , 5 , 6 ]. This is because of their relative ease of synthesis in one step from T F PP using a number of different methodologies (see below Scheme 2 ) and the multiple possibilities to derivatize the C 6 F 5 -groups by means of nucleophilic aromatic substitution reactions to, for example, render them water-soluble [ 6 , 7 , 8 ]. The presence of a ß,ß’-lactone moiety in carbaporphyrins [ 9 ], thiaporphyrins [ 10 , 11 ], octaalkylporphyrins [ 12 ], or subporphyrins [ 13 ] is known but much more rare and the utility of these compounds has not yet been shown.…”

“…Upon the replacement of one or two ß,ß’-bond(s) of the parent porphyrin by lactone moieties, the electronic structure of the chromophore is altered, sometimes in profound ways, even though the UV-vis spectra of free base TPP and TPL are surprisingly similar to each other [ 4 ]. The electronic influence of the lactone moieties on the chromophore was studied in some detail [ 4 , 5 , 6 , 14 , 15 , 16 ]. On account of only a minor steric interaction between the carbonyl oxygen and the o -hydrogen/fluorine atoms on a neighboring meso -aryl group, the introduction of one (or even two) lactone moieties alters the idealized planar conformation of the parent porphyrins only in subtle ways [ 4 , 14 , 16 , 17 , 18 ].…”

“…Like their porphyrin congeners [ 19 ], both TPL and T F PL are competent ligands for a wide range of metals, forming the metal complexes TPLM and T F PLM, respectively (with M = Mg II , Ni II , Mn III , Fe III , Zn II , Y III , Ag II , Pd II , Pt II , Yb III ) [ 4 , 5 , 6 , 20 , 21 , 22 , 23 ]. The metal ions may already be present in the metalloporphyrin/chlorin starting materials or are inserted later into the free base macrocycle.…”

“…Multiple distinct pathways of converting (metallo)porphyrins to (metallo)porpholactones were described in nearly two dozen individual papers. Some were specifically developed to provide porpholactones, others became the source of porpholactones by serendipity ( Scheme 2 ) [ 1 , 6 ]. For all methods, the exact mechanisms of the formation of porpholactones are not known.…”