Amphiphilic chlorins and bacteriochlorins in micellar environments. Molecular design, de novo synthesis, and photophysical properties

Abstract

The incorporation of amphiphilic tetrapyrrole macrocycles in organized media is of great value for a variety of fundamental photochemical studies, yet work to date has chiefly employed porphyrins rather than chlorins or bacteriochlorins. The latter absorb strongly in the red or near-infrared spectral region, respectively. Here, eight amphiphilic macrocycles (six chlorins and two bacteriochlorins) have been designed, synthesized and characterized; the compounds differ in long wavelength absorption (610-745 nm) and peripheral substituents (type of auxochrome, hydrophobic/hydrophilic groups). A methyl pyridinium or benzoic acid substituent at the 15-position provides a polar "tail" whereas a hydrophobic group distal thereto (in the chlorins) provides a lipophilic "head" for the spontaneous incorporation in organized media. The eight (bacterio)chlorins are characterized by static and time-resolved absorption and fluorescence spectroscopy in N,N-dimethylformamide (DMF) and three micellar environments (TX-100, CTAB, and SDS) as well as ultrafast transient absorption studies in DMF. In most cases, a long-lived excited singlet state was observed [free base chlorins (F f ¼ 0.14-0.20; s S ¼ 7.9-12.1 ns; F isc ¼ 0.5), zinc chlorins (F f ¼ 0.08-0.19; s S ¼ 2.0-3.4 ns; F isc ¼ 0.6-0.8) and free base bacteriochlorins (F f ¼ 0.06-0.16; s S ¼ 1.8-4.6 ns; F isc ¼ 0.4)]. In the case of bacteriochlorins, minimal medium dependence was observed whereas changing the hydrophilic group from methyl pyridinium to benzoic acid increases the fluorescence yield and excited-state lifetime by 50%. In the case of chlorins, the zinc chelate with methyl pyridinium substitution exhibits substantial environmental dependence due to interaction of the solvent with the methyl pyridinium group and the central zinc metal. Collectively, the studies provide valuable information for the design of red or near-infrared absorbing chromophores for incorporation into amphiphilic environments such as micelles, membranes, or proteins.

Amphiphilic BODIPY-Hydroporphyrin Energy Transfer Arrays with Broadly Tunable Absorption and Deep Red/Near-Infrared Emission in Aqueous Micelles

“…33 Photophysical properties of hydroporphyrins were also examined for energy-related applications in phospholipid membranes, SDS, or Triton X-100 micelles. 18,19,34–37 To the best of our knowledge, no synthetic, multichromophoric arrays, containing hydroporphyrins were studied in self-assembled micelles or bilayers.…”

Stable synthetic mono-substituted cationic bacteriochlorins mediate selective broad-spectrum photoinactivation of drug-resistant pathogens at nanomolar concentrations

“…The synthetic route also allows peripheral substituents to be tailored to vary the lipophilicity, polarity and overall charge (cationic, anionic or neutral) borne by the molecule [7]. The synthetic route to such bacteriochlorins as well as semisynthetic methods enable the synthesis of amphiphilic bacteriochlorins [8]. This synthetic versatility has enabled the design of photosensitizers that are able to kill cancer cells at extremely low concentrations upon activation by near-infrared light [9].…”

Modifications of Porphyrins and Hydroporphyrins for their Solubilization in Aqueous Media

“…Amphiphilic meso-pryridyl chlorins and bacteriochlorins, as described by the group of Lindsey [89] In an analogous manner, Anderson and co-workers employed a Suzuki coupling strategy to introduce pyridyl functional groups to meso-dibrominated bis-acetylene linked porphyrin dimer 49 (Scheme 13) [70]. After coupling with 4-pyridinylboronic acid, both meso-pyridyl functional groups in 50 were methylated under standard conditions to afford the dicationic product 51.…”

“…For instance, the group of Lindsey reported the synthesis of a series of amphiphilic hydroporphyrins prepared by Suzuki coupling of a pyridyl boronic ester with meso-bromo-chlorins or bacteriochlorins [34]. Key chlorin building block 45 was prepared by regioselective meso-bromination of chlorin 44 using NBS (Scheme 12) [89]. In the final step of the synthesis, the pyridyl functional group was quarternized with CH3I to furnish bacteriochlorin 46.…”

“…Using the same Suzuki coupling approach that was used to introduce pyridyl substituents to the meso-position (cf. Scheme 12), chlorins 85, 86 and the bacteriochlorin Preprints (www.preprints.org) | NOT PEER-REVIEWED | Posted: 6 June 2017 doi:10.20944/preprints201706.0032.v1 87 were prepared [89]. The carboxylate functionality was introduced in the free acid form, eliminating the need for the utilization of protecting groups.…”