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A Structurally-Tunable 3-Hydroxyflavone Motif for Visible Light-Induced Carbon Monoxide-Releasing Molecules (CORMs).

Anderson SN, Richards JM, Esquer HJ, Benninghoff AD, Arif AM, Berreau LM - ChemistryOpen (2015)

Bottom Line: Molecules that can be used to deliver a controlled amount of carbon monoxide (CO) have the potential to facilitate investigations into the roles of this gaseous molecule in biology and advance therapeutic treatments.This has led to the development of light-induced CO-releasing molecules (photoCORMs).Herein, we report a new biologically-inspired organic photoCORM motif that exhibits several features that are desirable in a next-generation photoCORM.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemistry & Biochemistry, Utah State University 0300 Old Main Hill, Logan, UT, 84322-0300, USA.

ABSTRACT
Molecules that can be used to deliver a controlled amount of carbon monoxide (CO) have the potential to facilitate investigations into the roles of this gaseous molecule in biology and advance therapeutic treatments. This has led to the development of light-induced CO-releasing molecules (photoCORMs). A goal in this field of research is the development of molecules that exhibit a combination of controlled CO release, favorable biological properties (e.g., low toxicity and trackability in cells), and structural tunability to affect CO release. Herein, we report a new biologically-inspired organic photoCORM motif that exhibits several features that are desirable in a next-generation photoCORM. We show that 3-hydroxyflavone-based compounds are easily synthesized and modified to impart changes in absorption features and quantum yield for CO release, exhibit low toxicity, are trackable in cells, and can exhibit both O2-dependent and -independent CO release reactivity.

No MeSH data available.


Related in: MedlinePlus

Absorption spectra of 4 and 6–8 in acetonitrile.
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fig04: Absorption spectra of 4 and 6–8 in acetonitrile.

Mentions: A key feature of the structural motif of 4 that distinguishes it from all previously described organic photoCORMs is the ease with which structural modifications can be introduced to tune its physical properties. For example, a dialkylamino substituent can be incorporated on the phenyl ring or the carbonyl oxygen can be substituted with sulfur to red-shift absorption features toward the therapeutic window. Dialkylamino-substituted flavonols have been previously used as environment-sensitive probes in biological systems.20 However, neutral flavonols of this type have not been previously shown to exhibit photoinduced CO-releasing reactivity. Flavothiones, have been reported to undergo O2-dependent photodegradation to give nontoxic byproducts, but these reactions have not been fully explored in terms of product identification.21 Molecules 6–8 were easily prepared using standard synthetic methods (Scheme 4) and were isolated in analytically pure forms via precipitation. Each compound was characterized by elemental analysis, UV-vis, fluorescence and IR spectroscopy, and mass spectrometry (Figures S13–S21 in the Supporting Information). These molecules exhibit red-shifted absorption features and higher molar absorptivity values than were observed for 4 (Figure 4). Quantitative CO release occurs when aerobic acetonitrile solutions of 6–8 are exposed to visible light (6 and 7: 419 nm; 8: >546 nm; Table 1). For compounds 6 and 7, O2-incorporated organic products akin to that found in the reaction of 4 were identified by 1H NMR and IR spectroscopy, and mass spectral analysis (Figures S22–S25 in the Supporting Information). The quantum yield associated with the reaction of 7 is significantly enhanced relative to that found for 4 (Table 1). The reaction involving 8 is noteworthy in that, while a full equivalent of CO is released under aerobic conditions, significant light-induced CO-release reactivity (0.32(7) equiv) also occurs under anaerobic conditions. Both the aerobic and anaerobic pathways for CO release from 8 result in the production of a mixture of products, including some that appear to result from photoisomerization reactivity (Figures S26–S27 in the Supporting Information). Photoinduced CO-release also occurs when 6–8 are dissolved in other solvents, including DMSO and 1:1 aqueous DMSO.


A Structurally-Tunable 3-Hydroxyflavone Motif for Visible Light-Induced Carbon Monoxide-Releasing Molecules (CORMs).

Anderson SN, Richards JM, Esquer HJ, Benninghoff AD, Arif AM, Berreau LM - ChemistryOpen (2015)

Absorption spectra of 4 and 6–8 in acetonitrile.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4608525&req=5

fig04: Absorption spectra of 4 and 6–8 in acetonitrile.
Mentions: A key feature of the structural motif of 4 that distinguishes it from all previously described organic photoCORMs is the ease with which structural modifications can be introduced to tune its physical properties. For example, a dialkylamino substituent can be incorporated on the phenyl ring or the carbonyl oxygen can be substituted with sulfur to red-shift absorption features toward the therapeutic window. Dialkylamino-substituted flavonols have been previously used as environment-sensitive probes in biological systems.20 However, neutral flavonols of this type have not been previously shown to exhibit photoinduced CO-releasing reactivity. Flavothiones, have been reported to undergo O2-dependent photodegradation to give nontoxic byproducts, but these reactions have not been fully explored in terms of product identification.21 Molecules 6–8 were easily prepared using standard synthetic methods (Scheme 4) and were isolated in analytically pure forms via precipitation. Each compound was characterized by elemental analysis, UV-vis, fluorescence and IR spectroscopy, and mass spectrometry (Figures S13–S21 in the Supporting Information). These molecules exhibit red-shifted absorption features and higher molar absorptivity values than were observed for 4 (Figure 4). Quantitative CO release occurs when aerobic acetonitrile solutions of 6–8 are exposed to visible light (6 and 7: 419 nm; 8: >546 nm; Table 1). For compounds 6 and 7, O2-incorporated organic products akin to that found in the reaction of 4 were identified by 1H NMR and IR spectroscopy, and mass spectral analysis (Figures S22–S25 in the Supporting Information). The quantum yield associated with the reaction of 7 is significantly enhanced relative to that found for 4 (Table 1). The reaction involving 8 is noteworthy in that, while a full equivalent of CO is released under aerobic conditions, significant light-induced CO-release reactivity (0.32(7) equiv) also occurs under anaerobic conditions. Both the aerobic and anaerobic pathways for CO release from 8 result in the production of a mixture of products, including some that appear to result from photoisomerization reactivity (Figures S26–S27 in the Supporting Information). Photoinduced CO-release also occurs when 6–8 are dissolved in other solvents, including DMSO and 1:1 aqueous DMSO.

Bottom Line: Molecules that can be used to deliver a controlled amount of carbon monoxide (CO) have the potential to facilitate investigations into the roles of this gaseous molecule in biology and advance therapeutic treatments.This has led to the development of light-induced CO-releasing molecules (photoCORMs).Herein, we report a new biologically-inspired organic photoCORM motif that exhibits several features that are desirable in a next-generation photoCORM.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemistry & Biochemistry, Utah State University 0300 Old Main Hill, Logan, UT, 84322-0300, USA.

ABSTRACT
Molecules that can be used to deliver a controlled amount of carbon monoxide (CO) have the potential to facilitate investigations into the roles of this gaseous molecule in biology and advance therapeutic treatments. This has led to the development of light-induced CO-releasing molecules (photoCORMs). A goal in this field of research is the development of molecules that exhibit a combination of controlled CO release, favorable biological properties (e.g., low toxicity and trackability in cells), and structural tunability to affect CO release. Herein, we report a new biologically-inspired organic photoCORM motif that exhibits several features that are desirable in a next-generation photoCORM. We show that 3-hydroxyflavone-based compounds are easily synthesized and modified to impart changes in absorption features and quantum yield for CO release, exhibit low toxicity, are trackable in cells, and can exhibit both O2-dependent and -independent CO release reactivity.

No MeSH data available.


Related in: MedlinePlus