Probing the Interactions of Porphyrins with Macromolecules Using NMR Spectroscopy Techniques

Abstract

Porphyrinic compounds are widespread in nature and play key roles in biological processes such as oxygen transport in blood, enzymatic redox reactions or photosynthesis. In addition, both naturally derived as well as synthetic porphyrinic compounds are extensively explored for biomedical and technical applications such as photodynamic therapy (PDT) or photovoltaic systems, respectively. Their unique electronic structures and photophysical properties make this class of compounds so interesting for the multiple functions encountered. It is therefore not surprising that optical methods are typically the prevalent analytical tool applied in characterization and processes involving porphyrinic compounds. However, a wealth of complementary information can be obtained from NMR spectroscopic techniques. Based on the advantage of providing structural and dynamic information with atomic resolution simultaneously, NMR spectroscopy is a powerful method for studying molecular interactions between porphyrinic compounds and macromolecules. Such interactions are of special interest in medical applications of porphyrinic photosensitizers that are mostly combined with macromolecular carrier systems. The macromolecular surrounding typically stabilizes the encapsulated drug and may also modify its physical properties. Moreover, the interaction with macromolecular physiological components needs to be explored to understand and control mechanisms of action and therapeutic efficacy. This review focuses on such non-covalent interactions of porphyrinic drugs with synthetic polymers as well as with biomolecules such as phospholipids or proteins. A brief introduction into various NMR spectroscopic techniques is given including chemical shift perturbation methods, NOE enhancement spectroscopy, relaxation time measurements and diffusion-ordered spectroscopy. How these NMR tools are used to address porphyrin–macromolecule interactions with respect to their function in biomedical applications is the central point of the current review.

Insight into Drug Loading Regulated Micellar Rigidity by Nuclear Magnetic Resonance

“…As shown in 1 H NMR spectra (Figures e and S7), the methyl proton peaks of both F127 (∼1.0 ppm) and IMC (∼2.0 ppm) in three IMC@F127 micelles shift the resonance upfield as compared with those of raw F127 (∼1.1 ppm, H d ) or IMC (∼2.1 ppm, H 12 ), and the chemical shift change augments along with the increase of drug loading, given that drug–polymer interaction during the self-assembly of IMC@F127 micelles leads to the shielding of resonance . The splitting of the methyl peak of F127 may result from the J-coupling effect with the adjacent methylene protons or the interaction between IMC and F127. , Figure f shows the thermogravimetric analysis (TGA) curves of IMC, F127, and three IMC@F127 micelles, where the different temperature ranges of 80–100 °C, 250–400 °C, and 350–400 °C correspond to the weight losses of water, , IMC, , and F127, respectively. The weight loss of water in HL micelles is far below the other two counterparts (phase I), implying the sharp decrease of micellar shell hydration with increasing drug loading .…”

“…32 The splitting of the methyl peak of F127 may result from the Jcoupling effect with the adjacent methylene protons or the interaction between IMC and F127. 33,34 Figure 4f shows the thermogravimetric analysis (TGA) curves of IMC, F127, and three IMC@F127 micelles, where the different temperature ranges of 80−100 °C, 250−400 °C, and 350−400 °C correspond to the weight losses of water, 35,36 IMC, 37,38 and F127, 39 respectively. The weight loss of water in HL micelles is far below the other two counterparts (phase I), implying the sharp decrease of micellar shell hydration with increasing drug loading.…”

Carboranes as unique pharmacophores in antitumor medicinal chemistry

“…Boronated porphyrins and their derivatives can preferentially accumulate in cancer cells with low dark cytotoxicity, 167 , 168 , 169 and thus have potential applications as BNCT/PDT dual sensitizers. 167 , 168 , 169 , 170 The Vicente group reported that boronated chlorin killed T98G cells of human glioma, 171 while Pandey and co-workers found that fluorinated substituents promoted photosensitivity. 172 It was also found that fluorinated porphyrins had higher photokinetic activity than their non-fluorinated counterparts.…”

Zinc, Tin and Silver Porphyrins (TPP, TCPP, TMPP, THPP, TPPS, TMPyP) as photosensitizers in antibacterial photodynamic therapy for chronic wounds: A screening study

“…Porphyrin molecules exhibit molecular flexibility (Cheng et al, 1997) and adopt various conformations (Kingsbury and Senge, 2021). The interactions between the four + N-CH3 groups and the ring current affects the out-of-plane distortion of the compound which results in the protons of the + N-CH3 groups being in different chemical environments, creating the two peaks, δ = 1.08 and δ = 1.20 in the TMPyP (Gjuroski et al, 2021).…”