Supramolecular Control of Singlet Oxygen Generation

Abstract

Singlet oxygen (¹O₂) is the excited state electronic isomer and a reactive form of molecular oxygen, which is most efficiently produced through the photosensitized excitation of ambient triplet oxygen. Photochemical singlet oxygen generation (SOG) has received tremendous attention historically, both for its practical application as well as for the fundamental aspects of its reactivity. Applications of singlet oxygen in medicine, wastewater treatment, microbial disinfection, and synthetic chemistry are the direct results of active past research into this reaction. Such advancements were achieved through design factors focused predominantly on the photosensitizer (PS), whose photoactivity is relegated to self-regulated structure and energetics in ground and excited states. However, the relatively new supramolecular approach of dictating molecular structure through non-bonding interactions has allowed photochemists to render otherwise inactive or less effective PSs as efficient ¹O₂ generators. This concise and first of its kind review aims to compile progress in SOG research achieved through supramolecular photochemistry in an effort to serve as a reference for future research in this direction. The aim of this review is to highlight the value in the supramolecular photochemistry approach to tapping the unexploited technological potential within this historic reaction.

Keywords: calixarene; cavitands; cucurbituril; cyclodextrin; near IR (NIR); oxidation; photodynamic therapy (PDT); photosensitizer (PS); singlet oxygen; singlet oxygen generation (SOG); supramolecular chemistry.

Figure 1

Biological and therapeutic applications of singlet oxygen.

Figure 2

Chemical reactions affected by singlet oxygen.

Figure 3

Molecular orbital energy diagram for the two excited singlet states of oxygen (left, and middle) and triplet ground state.

Figure 4

Relative arrangement of electronic states of molecular oxygen.

Figure 5

Jablonski diagram representing singlet oxygen generation through triplet energy transfer from photosensitizer.

Figure 6

Chemical structures of common molecular cavitands used to control excited-stated chemistry of organic molecules.

Figure 7

Representations of cavitands frequently used in controlling singlet oxygen generation efforts. Color coding: red (oxygen), blue (nitrogen), green (carbon), yellow (sulfur). Hydrogens are omitted for clarity.

Figure 8

(Left) Cavitand-based activatable photosensitizer (aPS) assembly for singlet oxygen generation and simultaneous imaging. (Right) Utility of aPS for simultaneous cellular PDT and imaging. Image used with permission from original work [50].

Figure 9

(A) Oxidation reaction used to monitor singlet oxygen generation. (B) Trends in singlet oxygen generation based on absorbance of ADPA alone (black), and ADPA with TB-B (on state, red) and ADPA, TB-B, CB8 and binding competitor (off state, blue). (C) Mechanism of energy and electron transfer pathways for on/off state. Images used with permission from published work [50].

Figure 10

Cucurbituril-mediated enhancement of singlet oxygen generation efficiency of naphthyl TPOR: Structure of TPOR and complexation of CB to form TPOR-CB8 network [51].

Figure 11

(A) Reaction used for monitoring SOG by TPOR@CB8 self-assembled polymer. (B) TEMPO EPR signal for uncomplexed (black) and complexed (red) TPOR. (C) Plot of time-dependent change in TPOR oxidation. Images used with permission from published work [51].

Figure 12

(Left) Chemical structure of CPTC and its complexation with host to form CPTC@β-CD₂ complex. (Middle) Complexation-induced changes in UV-Vis absorption spectrum. (Right) Energy-minimized structure of complex. Image used with permission from published work [52].

Figure 13

(A) Depiction of cucurbituril-TPOR complex capable of generating singlet oxygen for bacterial disinfection. (B) Comparison of TPOR’s SOG in the presence (circle) and absence (square) of CB8 as monitored through EPR spectroscopy of TEMP oxidation to TEMPO. Images used with permission from published work [53].

Figure 14

(A) Depiction of 5R-POR complex formation for singlet oxygen generation. (B) Absorption and emission spectra of the uncomplexed POR. (C) Redox reaction with singlet oxygen used to monitor its generation. (D,E) Emission intensity change and its plot for singlet oxygen monitoring. Images used with permission from published work [54].

Figure 15

(A) Schematic representation of methylene blue complexing to CB7. (B) Photo-dynamics of singlet oxygen generation by free and bound MB. (C,D) Spectral monitoring of singlet oxygen generation and its plotting in the absence (O) or presence (●) of CB7. Images used with permission from published work [55].

Figure 16

(A) Adamantyl phthalocyanine (Adm-PC) bound to the surface cavity of CD-V nanoparticle. (B) Formation of CD-V nanoparticle by tethered CD and representation of overall complexed structure. (C,D) Spectra of free (red) and bound (black) Adm-PC. (E,F) Monitoring of singlet oxygen generation through spectral changes of ADMADM oxidation and its plot. Images used with permission from published work [56].

Figure 17

(A) Structure of the components of supramolecular assembly. (B) Process of the self-assembled micellar nanoparticle. (C) Utility of the porphyrin-embedded nanoparticle in tumor cytotoxicity. Used with permission from published work [57].

Figure 18

(A) Structure of donor and acceptor/switch units in on/off SOG switch. (B) Self-assembled structure and their photoreversibility, depiction of assembly embedded within nanoparticle and its SOG. (C) Fluorescence response from SOSG assay of the metallacycle embedded within NPs showing high SOG efficiency with DTC-A in open form (red) compared to the closed form (blue). (D) Switching between on/off cycle with UV and visible light and their SOG efficiency with SOSG. Images used with permission from published work [58].

Figure 19

Energy diagram depicting relative energies of Por-D, DTC-A in open and closed forms controlling the on/off mode. Images used with permission from published work [58].

Figure 20

Structure of DIET-CD host (A) and porphyrin guest (C). (B) Photochromic switch dynamics based on the host–guest polymer formation and FRET process and alternating between on/off states with visible/UV lights. (D) Change in fluorescence over time when open form is exposed to UV light. (E) Switching between the states as monitored through 1283 nm singlet oxygen phosphorescence. Images used with permission from published work [59].

Figure 21

(A) The turn on/off of TBO affected through cavitand complexation and competitive guest Mem. (B) Fluorescence of ADMADM used to monitor SOG generated when TBO⁺ is exposed to light in the absence of any CBs (red), in the presence of 10.25 eq. of CB7 (dark blue squares) and 8.1 eq. of CB8 (light blue triangle). Images used with permission from published work [60].

Figure 22

Formation of nanoparticle through supramolecular inclusion of azo diphenyl guest and CA-POR. Cytotoxic effect of the NP nanoparticle through its SOG efficiency. Image used with permission from published work [61].

Figure 23

(A) Enhancement of SOG for BODIPY dye (BO-1) enhanced upon binding to CB7. (B) Fluorescence of DCHF increase used to monitor SOG for free and bound BO-1. (C) Photobleaching trend based on DCHF fluorescence indicating self-termination of the dye. (D) Triplet lifetimes of free (left) and complexed (right) BO-1. Image used with permission from published work [62].

Figure 24

(A) Components of nanocomposite for SOG: BO-1, heavy-atom perturbers (DIB, TIM, TIE), and chitosan matrix (chi). (B) Depiction of the supramolecularly influenced SOG nanocomposite. (C) Mechanism of singlet oxygen generation and its reaction with DHN for monitoring. (D) Change in DHN and juglone mixture absorbance (signal from other species subtracted) with time for monitoring SOG. Image used with permission from published work [63].

Figure 25

(A) Structures of donor, acceptor, and polymer used for construction of nanoreactor for intracellular singlet oxygen sensitization. (B) Emission spectra of nanoparticles containing donor and acceptor as emission of acceptor BO-2 observed upon excitation of donor DPA (a,b). Emission intensity of donor DPA corresponding to spectra (c,d), which decrease in presence of acceptor. (C) NIR emission of singlet oxygen generated when both donor and acceptor are present (e) vs. when only donor (g) or acceptor (f) is present. Image used with permission from published work [64].

Figure 26

(A) Formation of supramolecular C₆₀ dyad. (B) Mechanism of dyad function for SOG. (C) Monitoring of SOG through absorbance of DHN oxidation to juglone for free CBP (solid line, blue) vs. C₆₀-CBP complex (broken line, red). Image used with permission from published work [73].

Figure 27

(A) Ene reactions and their product distribution in homogeneous media and within OA. (B) Structure of methyl cyclohexene with OA. (C) Mechanism of reaction selectivity deduced from supramolecular analysis. Image used with permission from published work [74].