Porphyrinoid Drug Conjugates

Abstract

Drawing inspiration from nature today remains a time-honored means of discovering the therapies of tomorrow. Porphyrins, the so-called ''pigments of life'' have played a key role in this effort due to their diverse and unique properties. They have seen use in a number of medically relevant applications, including the development of so-called drug conjugates wherein functionalization with other entities is used to improve efficacy while minimizing dose limiting side effects. In this Perspective, we highlight opportunities associated with newer, completely synthetic analogs of porphyrins, commonly referred to as porphyrinoids, as the basis for preparing drug conjugates. Many of the resulting systems show improved medicinal or site-localizing properties. As befits a Perspective of this type, our efforts to develop cancer-targeting, platinum-containing conjugates based on texaphyrins (a class of so-called ''expanded porphyrins'') will receive particular emphasis; however, the promise inherent in this readily generalizable approach will also be illustrated briefly using two other common porphyrin analogs, namely the corroles (a ''contracted porphyrin'') and porphycene (an ''isomeric porphyrin'').

Corroles at work: a small macrocycle for great applications

“…[235][236][237][238][239][240][241] Corrole conjugates have been the subject of a recent review from Sessler and coworker. 242 Main group corroles and their photophysical properties have been recently reviewed by Gross and Churchill. 243 The correlation between the molecular structures of three free-base A 3 -corroles (e.g.…”

Graphene quantum dot-porphyrin/phthalocyanine multifunctional hybrid systems: from interfacial dialogue to application

“…Pp/Pc-based GQD nanohybrids can be implemented in a myriad of applications based on photosensitizers (PSs) for PDT, 46,47 photocatalysis, electrocatalysis, and sensing 48,49 due to the biomimetic photophysical, electrochemical, 50 and bioactive characteristics of Pp with improved efficacy 2,51 (Fig. 5).…”

“…Particularly, in PDT, 54 the optical properties and photosensitizer 55 can be enhanced to improve its efficacy with site-localized properties through curtailing the dose-limit side effects. 29,36,37,41,51,56 This will also avoid or abate chemical degradation in the physiological system. 57…”

Modular Synthesis of Tetraurea and Octaurea Macrocycles Encoded with Specific Monomer Sequences

“…1 Through elegant molecular designs and synthetic methodologies, 2,3 various macrocyclic structures have been made and engineered with specific monomer sequences for the uses of molecular recognition, [4][5][6] chemical storage and separation, 7,8 catalysis, [9][10][11] molecular machines, 12 assemblies, [13][14][15][16] and adaptive materials. [17][18][19] Benefitting from the characteristic hydrogen bonding nature (high-rigidity and self-complementarity) of the urea unit, 20,21 urea-based macrocycles have attracted great attention in the studies of anion recognition [22][23][24][25][26] and hierarchical assembly. [27][28][29] However, compared to the well-established industrialization of polyurea elastomer materials, 30 the oligourea macrocycles are far less explored because the intermolecular hydrogen bonding of urea units may induce poor solubility of the desired macrocycles thus inhibiting their syntheses and purifications.…”