Eunkyung Yang - Academia.edu (original) (raw)
Papers by Eunkyung Yang
New J. Chem., 2015
ABSTRACT Bacteriochlorins are potentially excellent chromophores for near-infrared (NIR) photoche... more ABSTRACT Bacteriochlorins are potentially excellent chromophores for near-infrared (NIR) photochemical and spectroscopic studies yet the intrinsically hydrophobic macrocycle core has stymied work in aqueous media. Herein, a set of bacteriochlorins bearing distinct polar motifs is reported. The motifs include phosphonate (pH-dependent anionic, BC1), carboxylate (pH-dependent anionic, BC2), ammonium (permanently cationic) without (BC3) or with (BC4) a linker ester moiety, and tetraethyleneoxy (a short PEG, polar non-ionic, BC5). The groups are located at the 3,5-positions of each of two aryl groups at the bacteriochlorin 3,13-sites. Synthesis of the bacteriochlorins entails the Suzuki coupling of a common 3,13-dibromobacteriochlorin building block with a set of aryl boronates. Five factors were selected for comparisons among the polar motifs upon attachment to the bacteriochlorins: (1) synthesis yield and ease of purification, (2) amenability toward subsequent derivatization, (3) water-solubility, (4) full-width-at-half-maximum (fwhm) of the long-wavelength (Qy) absorption and fluorescence bands, singlet excited-state lifetime (τS) and fluorescence quantum yield (Φf), and (5) stability in the dark or under illumination. Water-solubility was assessed by examination of the absorption spectra across a 1000-fold concentration range (0.2–0.6 μM to 200–600 μM). With the exception of BC4, all displayed good aqueous solubility, photostability, and photophysical properties in aqueous solution (fwhm = 23–31 nm, Φf = 0.10–0.16, τS = 1.9–2.7 ns). The modestly lower Φf and τS values for the bacteriochlorins in aqueous versus organic (N,N-dimethylformamide) media are traced to an increased rate constant for excited-state internal conversion. Upon consideration of all factors, the ammonium (short linker) and short PEG groups were most attractive for solubilization of the bacteriochlorins in aqueous media. The studies prompted the synthesis of two water-soluble (ammonium-substituted) bacteriochlorins bearing N-hydroxysuccinimide esters.
The journal of physical chemistry. B, Jan 26, 2015
Six new bacteriochlorins expanding the range of the strong near-infrared (NIR) absorption (Qy ban... more Six new bacteriochlorins expanding the range of the strong near-infrared (NIR) absorption (Qy band) to both shorter and longer wavelengths (∼690 to ∼900 nm) have been synthesized and characterized. The architectures include bacteriochlorin-bisimides that have six-membered imide rings spanning the 3,5- and 13,15-macrocycle positions or five-membered imide rings spanning the β-pyrrolic 2,3- and 12,13-positions. Both bisimide types absorb at significantly longer wavelength than the bacteriochlorin precursors (no fused rings), whereas oxo-groups at the 7- or 7,17-positions shift the Qy band to a new short wavelength limit. Surprisingly, bacteriochlorin-bisimides with five-membered β-pyrrolic-centered imide rings have a Qy band closer to that of six-membered bacteriochlorin-monoimides. However, the five-membered bisimides (versus the six-membered bacteriochlorin-monoimides) have significantly enhanced absorption intensity that is paralleled by an ∼2-fold higher fluorescence yield (∼0.16 ...
Photochemistry and Photobiology, 2013
Photophysical, photostability, electrochemical and molecular-orbital characteristics are analyzed... more Photophysical, photostability, electrochemical and molecular-orbital characteristics are analyzed for a set of stable dicyanobacteriochlorins that are promising photosensitizers for photodynamic therapy (PDT). The bacteriochlorins are the parent compound (BC), dicyano derivative (NC)2BC and corresponding zinc (NC)2BC-Zn and palladium chelate (NC)2BC-Pd. The order of PDT activity against HeLa human cancer cells in vitro is (NC)2BC-Pd > (NC)2BC > (NC)2BC-Zn ≈ BC. The near-infrared absorption feature of each dicyanobacteriochlorin is bathochromically shifted 35-50 nm (748-763 nm) from that for BC (713 nm). Intersystem crossing to the PDT-active triplet excited state is essentially quantitative for (NC)2BC-Pd. Phosphorescence from (NC)2BC-Pd occurs at 1122 nm (1.1 eV). This value and the measured ground-state redox potentials fix the triplet excited-state redox properties, which underpin PDT activity via Type-1 (electron transfer) pathways. A perhaps counterintuitive (but readily explicable) result is that of the three dicyanobacteriochlorins, the photosensitizer with the shortest triplet lifetime (7 μs), (NC)2BC-Pd has the highest activity. Photostabilities of the dicyanobacteriochlorins and other bacteriochlorins studied recently are investigated and discussed in terms of four phenomena: aggregation, reduction, oxidation and chemical reaction. Collectively, the results and analysis provide fundamental insights concerning the molecular design of PDT agents.
The Journal of Physical Chemistry B, 2014
The synthesis, photophysical, redox, and molecular-orbital characteristics of three perylene-tetr... more The synthesis, photophysical, redox, and molecular-orbital characteristics of three perylene-tetrapyrrole dyads were investigated to probe the efficacy of the arrays for use as light-harvesting constituents. Each dyad contains a common perylene-monoimide that is linked at the N-imide position via an arylethynyl group to the meso-position of the tetrapyrrole. The tetrapyrroles include a porphyrin, chlorin, and bacteriochlorin, which have zero, one, and two reduced pyrrole rings, respectively. The increased pyrrole-ring reduction results in a progressive red shift and intensification of the lowest-energy absorption band, as exemplified by benchmark monomers. The arylethyne linkage affords moderate perylene-tetrapyrrole electronic coupling in the dyads as evidenced by the optical, molecular-orbital, and redox properties of the components of the dyads versus the constituent parts. All three dyads in nonpolar solvents exhibit relatively fast (subpicosecond) energy transfer from the perylene to the tetrapyrrole. Competing charge-transfer processes are also absent in nonpolar solvents, but become active for both the chlorin and bacteriochlorin-containing dyads in polar solvents. Calculations of energy-transfer rates via the Förster, through-space mechanism reveal that these rates are, on average, 3-fold slower than the observed rates. Thus, the Dexter through-bond mechanism contributes more substantially than the through-space mechanism to energy transfer in the dyads. The electronic communication between the perylene and tetrapyrrole falls in a regime intermediate between those operative in other classes of perylene-tetrapyrrole dyads that have previously been studied.
The Journal of Physical Chemistry B, 2013
The synthesis, photophysical, redox, and molecular-orbital characteristics of three perylene-tetr... more The synthesis, photophysical, redox, and molecular-orbital characteristics of three perylene-tetrapyrrole dyads were investigated to elucidate characteristics favorable for use in next-generation light-harvesting assemblies. Each dyad contains a common perylene-monoimide that is linked at the 9-position via an ethynyl group to the meso-position of the tetrapyrrole. The tetrapyrroles include a porphyrin, chlorin, and bacteriochlorin, which have zero, one, and two reduced pyrrole rings, respectively. The increased pyrrole-ring reduction results in a progressive red shift and intensification of the lowest-energy absorption band, as exemplified by benchmark monomers. The direct ethyne linkage and accompanying strong perylene-tetrapyrrole electronic coupling in the dyads is evident by significant differences in optical absorption versus the sum of the features of the constituents. The perturbations decrease for the tetrapyrrole constituent along the series porphyrin > chlorin > bacteriochlorin. This trend is explained by the relative configurational mixing in the tetrapyrrole excited states and how the configuration-interaction energy (and not simply the energies of the configurations) is affected by coupling to the perylene. The perylene-tetrapyrrole electronic coupling is further evidenced in the redox and MO characteristics of the three dyads. All three dyads in nonpolar solvents exhibit relatively long singlet excited-state lifetimes (3.3-6.5 ns) and relatively large fluorescence quantum yields (0.14-0.40). Collectively, the physicochemical characteristics of the strongly coupled perylene-tetrapyrrole dyads render these architectures excellent candidates for light-harvesting materials with significant, even panchromatic, near-ultraviolet to near-infrared absorption.
The Journal of Physical Chemistry B, 2010
Photochemical & Photobiological Sciences, 2014
Synthetic chlorins can accommodate diverse substituents about the macrocycle perimeter. Simple au... more Synthetic chlorins can accommodate diverse substituents about the macrocycle perimeter. Simple auxochromes (e.g., vinyl, acetyl, phenyl) allow systematic tuning of spectral and photophysical features. More extensive spectral tailoring may be achieved by using more potent, highly conjugated substituents that themselves bring new absorption into a target spectral region, if deleterious excited-state quenching processes can be avoided. To explore such an expanded substituent space, herein the spectral and photophysical properties of four chlorin-chalcones are reported. The molecules are free base and zinc chlorins with substituents at the 13-position that include a chalcone and an extended chalcone derived by reaction of the 13-acetylchlorin with benzaldehyde and all-trans-retinal, respectively. Measurements of the spectral and photophysical properties (Φ f , τ s , k f , k ic , k isc ) are accompanied by density functional calculations that examine the characteristics of the frontier molecular orbitals. The chlorin-chalcones in nonpolar (toluene) and polar (dimethylsulfoxide) media exhibit bathochromically shifted (and intense) Q y absorption bands. The presence of the retinylidene group adds new absorption in the blue-green region where the chlorins are typically transparent; excitation in this region leads to quantitative formation of the chlorin Q y excited state. The spectral properties generally correlate with substituent effects on the frontier MOs. The four chlorin-chalcones in the solvent toluene have high fluorescence yields (0.24-0.30) and multinanosecond singlet excited-state lifetimes (3.7-8.4 ns), in addition to the added absorption imparted by the chalcone moiety. Collectively, the studies reported herein provide insight into the fundamental properties of chlorins and illustrate the utility of chalcones as a means of both tuning and augmenting the spectral properties of these chromophores. † Electronic supplementary information (ESI) available: Synthesis procedures and characterization data. See
New Journal of Chemistry, 2011
ABSTRACT Bacteriochlorophylls contain the bacteriochlorinchromophore and a fifth, five-membered o... more ABSTRACT Bacteriochlorophylls contain the bacteriochlorinchromophore and a fifth, five-membered oxopentano ring that encompasses positions 13–15 known as the “isocyclic” ring E. Such bacterio-131-oxophorbines have heretofore only been available in the naturally occurring compounds, and analogues bearing six-membered rings have only been available by derivatization of bacteriochlorophylls. A de novo route to synthetic bacteriochlorins, which bear a geminal dimethyl group in each pyrroline ring, has been extended to gain access to a bacterio-131-oxophorbine and bacteriochlorin-13,15-dicarboximides. The route relies on acid-catalyzed condensation of a dihydrodipyrrin-acetal to form the bacteriochlorin, which then is subjected to regioselective 15-bromination. Pd-mediated cyclization of the 15-bromobacteriochlorin bearing a 13-acetylgroup (intramolecular α-arylation) or 13-ethoxycarbonylgroup (carbamoylation and intramolecular imidation) gives the bacterio-131-oxophorbine or bacteriochlorin-13,15-dicarboximide, respectively. The resulting macrocycles exhibit absorption in the near-infrared spectral region (733–818 nm), which extends the spectral coverage beyond that obtained previously with synthetic bacteriochlorins that lack a fifth ring. The macrocycles also exhibit excited singlet-state lifetimes (1.9–4.6 ns) comparable to or longer than those of natural photosynthetic pigments. Density functional theory calculations predict that the bathochromically shifted absorption is primarily due to lowering of the energy of the lowest unoccupied molecular orbital. The new route complements existing semisynthetic routes and should enable fundamental spectroscopic studies and diverse photochemical applications.
Journal of Medicinal Chemistry, 2010
Photodynamic therapy (PDT) is a rapidly developing approach to treating cancer that combines harm... more Photodynamic therapy (PDT) is a rapidly developing approach to treating cancer that combines harmless visible and near-infrared light with a nontoxic photoactivatable dye, which upon encounter with molecular oxygen generates the reactive oxygen species that are toxic to cancer cells. Bacteriochlorins are tetrapyrrole compounds with two reduced pyrrole rings in the macrocycle. These molecules are characterized by strong absorption features from 700 to >800 nm, which enable deep penetration into tissue. This report describes testing of 12 new stable synthetic bacteriochlorins for PDT activity. The 12 compounds possess a variety of peripheral substituents and are very potent in killing cancer cells in vitro after illumination. Quantitative structure-activity relationships were derived, and subcellular localization was determined. The most active compounds have both low dark toxicity and high phototoxicity. This combination together with near-infrared absorption gives these bacteriochlorins great potential as photosensitizers for treatment of cancer.
ChemMedChem, 2012
Photodynamic therapy (PDT) is a rapidly developing cancer therapy that utilizes the combination o... more Photodynamic therapy (PDT) is a rapidly developing cancer therapy that utilizes the combination of a nontoxic dye, termed a photosensitizer (PS), and harmless visible or near-infrared (NIR) light to kill cancer cells and destroy tumors by generating reactive oxygen species (ROS), such as singlet oxygen, superoxide and hydroxyl radical. PDT has the advantage of dual selectivity in that the PS can be targeted to its destination cell or tissue and the illumination can be spatially directed to the lesion. The ROS produced during PDT are effective in killing both malignant and normal cells via necrosis, apoptosis or autophagy, depending on the cell type, structure of the PS, and the light parameters chosen.
New J. Chem., 2015
ABSTRACT Bacteriochlorins are potentially excellent chromophores for near-infrared (NIR) photoche... more ABSTRACT Bacteriochlorins are potentially excellent chromophores for near-infrared (NIR) photochemical and spectroscopic studies yet the intrinsically hydrophobic macrocycle core has stymied work in aqueous media. Herein, a set of bacteriochlorins bearing distinct polar motifs is reported. The motifs include phosphonate (pH-dependent anionic, BC1), carboxylate (pH-dependent anionic, BC2), ammonium (permanently cationic) without (BC3) or with (BC4) a linker ester moiety, and tetraethyleneoxy (a short PEG, polar non-ionic, BC5). The groups are located at the 3,5-positions of each of two aryl groups at the bacteriochlorin 3,13-sites. Synthesis of the bacteriochlorins entails the Suzuki coupling of a common 3,13-dibromobacteriochlorin building block with a set of aryl boronates. Five factors were selected for comparisons among the polar motifs upon attachment to the bacteriochlorins: (1) synthesis yield and ease of purification, (2) amenability toward subsequent derivatization, (3) water-solubility, (4) full-width-at-half-maximum (fwhm) of the long-wavelength (Qy) absorption and fluorescence bands, singlet excited-state lifetime (τS) and fluorescence quantum yield (Φf), and (5) stability in the dark or under illumination. Water-solubility was assessed by examination of the absorption spectra across a 1000-fold concentration range (0.2–0.6 μM to 200–600 μM). With the exception of BC4, all displayed good aqueous solubility, photostability, and photophysical properties in aqueous solution (fwhm = 23–31 nm, Φf = 0.10–0.16, τS = 1.9–2.7 ns). The modestly lower Φf and τS values for the bacteriochlorins in aqueous versus organic (N,N-dimethylformamide) media are traced to an increased rate constant for excited-state internal conversion. Upon consideration of all factors, the ammonium (short linker) and short PEG groups were most attractive for solubilization of the bacteriochlorins in aqueous media. The studies prompted the synthesis of two water-soluble (ammonium-substituted) bacteriochlorins bearing N-hydroxysuccinimide esters.
The journal of physical chemistry. B, Jan 26, 2015
Six new bacteriochlorins expanding the range of the strong near-infrared (NIR) absorption (Qy ban... more Six new bacteriochlorins expanding the range of the strong near-infrared (NIR) absorption (Qy band) to both shorter and longer wavelengths (∼690 to ∼900 nm) have been synthesized and characterized. The architectures include bacteriochlorin-bisimides that have six-membered imide rings spanning the 3,5- and 13,15-macrocycle positions or five-membered imide rings spanning the β-pyrrolic 2,3- and 12,13-positions. Both bisimide types absorb at significantly longer wavelength than the bacteriochlorin precursors (no fused rings), whereas oxo-groups at the 7- or 7,17-positions shift the Qy band to a new short wavelength limit. Surprisingly, bacteriochlorin-bisimides with five-membered β-pyrrolic-centered imide rings have a Qy band closer to that of six-membered bacteriochlorin-monoimides. However, the five-membered bisimides (versus the six-membered bacteriochlorin-monoimides) have significantly enhanced absorption intensity that is paralleled by an ∼2-fold higher fluorescence yield (∼0.16 ...
Photochemistry and Photobiology, 2013
Photophysical, photostability, electrochemical and molecular-orbital characteristics are analyzed... more Photophysical, photostability, electrochemical and molecular-orbital characteristics are analyzed for a set of stable dicyanobacteriochlorins that are promising photosensitizers for photodynamic therapy (PDT). The bacteriochlorins are the parent compound (BC), dicyano derivative (NC)2BC and corresponding zinc (NC)2BC-Zn and palladium chelate (NC)2BC-Pd. The order of PDT activity against HeLa human cancer cells in vitro is (NC)2BC-Pd > (NC)2BC > (NC)2BC-Zn ≈ BC. The near-infrared absorption feature of each dicyanobacteriochlorin is bathochromically shifted 35-50 nm (748-763 nm) from that for BC (713 nm). Intersystem crossing to the PDT-active triplet excited state is essentially quantitative for (NC)2BC-Pd. Phosphorescence from (NC)2BC-Pd occurs at 1122 nm (1.1 eV). This value and the measured ground-state redox potentials fix the triplet excited-state redox properties, which underpin PDT activity via Type-1 (electron transfer) pathways. A perhaps counterintuitive (but readily explicable) result is that of the three dicyanobacteriochlorins, the photosensitizer with the shortest triplet lifetime (7 μs), (NC)2BC-Pd has the highest activity. Photostabilities of the dicyanobacteriochlorins and other bacteriochlorins studied recently are investigated and discussed in terms of four phenomena: aggregation, reduction, oxidation and chemical reaction. Collectively, the results and analysis provide fundamental insights concerning the molecular design of PDT agents.
The Journal of Physical Chemistry B, 2014
The synthesis, photophysical, redox, and molecular-orbital characteristics of three perylene-tetr... more The synthesis, photophysical, redox, and molecular-orbital characteristics of three perylene-tetrapyrrole dyads were investigated to probe the efficacy of the arrays for use as light-harvesting constituents. Each dyad contains a common perylene-monoimide that is linked at the N-imide position via an arylethynyl group to the meso-position of the tetrapyrrole. The tetrapyrroles include a porphyrin, chlorin, and bacteriochlorin, which have zero, one, and two reduced pyrrole rings, respectively. The increased pyrrole-ring reduction results in a progressive red shift and intensification of the lowest-energy absorption band, as exemplified by benchmark monomers. The arylethyne linkage affords moderate perylene-tetrapyrrole electronic coupling in the dyads as evidenced by the optical, molecular-orbital, and redox properties of the components of the dyads versus the constituent parts. All three dyads in nonpolar solvents exhibit relatively fast (subpicosecond) energy transfer from the perylene to the tetrapyrrole. Competing charge-transfer processes are also absent in nonpolar solvents, but become active for both the chlorin and bacteriochlorin-containing dyads in polar solvents. Calculations of energy-transfer rates via the Förster, through-space mechanism reveal that these rates are, on average, 3-fold slower than the observed rates. Thus, the Dexter through-bond mechanism contributes more substantially than the through-space mechanism to energy transfer in the dyads. The electronic communication between the perylene and tetrapyrrole falls in a regime intermediate between those operative in other classes of perylene-tetrapyrrole dyads that have previously been studied.
The Journal of Physical Chemistry B, 2013
The synthesis, photophysical, redox, and molecular-orbital characteristics of three perylene-tetr... more The synthesis, photophysical, redox, and molecular-orbital characteristics of three perylene-tetrapyrrole dyads were investigated to elucidate characteristics favorable for use in next-generation light-harvesting assemblies. Each dyad contains a common perylene-monoimide that is linked at the 9-position via an ethynyl group to the meso-position of the tetrapyrrole. The tetrapyrroles include a porphyrin, chlorin, and bacteriochlorin, which have zero, one, and two reduced pyrrole rings, respectively. The increased pyrrole-ring reduction results in a progressive red shift and intensification of the lowest-energy absorption band, as exemplified by benchmark monomers. The direct ethyne linkage and accompanying strong perylene-tetrapyrrole electronic coupling in the dyads is evident by significant differences in optical absorption versus the sum of the features of the constituents. The perturbations decrease for the tetrapyrrole constituent along the series porphyrin > chlorin > bacteriochlorin. This trend is explained by the relative configurational mixing in the tetrapyrrole excited states and how the configuration-interaction energy (and not simply the energies of the configurations) is affected by coupling to the perylene. The perylene-tetrapyrrole electronic coupling is further evidenced in the redox and MO characteristics of the three dyads. All three dyads in nonpolar solvents exhibit relatively long singlet excited-state lifetimes (3.3-6.5 ns) and relatively large fluorescence quantum yields (0.14-0.40). Collectively, the physicochemical characteristics of the strongly coupled perylene-tetrapyrrole dyads render these architectures excellent candidates for light-harvesting materials with significant, even panchromatic, near-ultraviolet to near-infrared absorption.
The Journal of Physical Chemistry B, 2010
Photochemical & Photobiological Sciences, 2014
Synthetic chlorins can accommodate diverse substituents about the macrocycle perimeter. Simple au... more Synthetic chlorins can accommodate diverse substituents about the macrocycle perimeter. Simple auxochromes (e.g., vinyl, acetyl, phenyl) allow systematic tuning of spectral and photophysical features. More extensive spectral tailoring may be achieved by using more potent, highly conjugated substituents that themselves bring new absorption into a target spectral region, if deleterious excited-state quenching processes can be avoided. To explore such an expanded substituent space, herein the spectral and photophysical properties of four chlorin-chalcones are reported. The molecules are free base and zinc chlorins with substituents at the 13-position that include a chalcone and an extended chalcone derived by reaction of the 13-acetylchlorin with benzaldehyde and all-trans-retinal, respectively. Measurements of the spectral and photophysical properties (Φ f , τ s , k f , k ic , k isc ) are accompanied by density functional calculations that examine the characteristics of the frontier molecular orbitals. The chlorin-chalcones in nonpolar (toluene) and polar (dimethylsulfoxide) media exhibit bathochromically shifted (and intense) Q y absorption bands. The presence of the retinylidene group adds new absorption in the blue-green region where the chlorins are typically transparent; excitation in this region leads to quantitative formation of the chlorin Q y excited state. The spectral properties generally correlate with substituent effects on the frontier MOs. The four chlorin-chalcones in the solvent toluene have high fluorescence yields (0.24-0.30) and multinanosecond singlet excited-state lifetimes (3.7-8.4 ns), in addition to the added absorption imparted by the chalcone moiety. Collectively, the studies reported herein provide insight into the fundamental properties of chlorins and illustrate the utility of chalcones as a means of both tuning and augmenting the spectral properties of these chromophores. † Electronic supplementary information (ESI) available: Synthesis procedures and characterization data. See
New Journal of Chemistry, 2011
ABSTRACT Bacteriochlorophylls contain the bacteriochlorinchromophore and a fifth, five-membered o... more ABSTRACT Bacteriochlorophylls contain the bacteriochlorinchromophore and a fifth, five-membered oxopentano ring that encompasses positions 13–15 known as the “isocyclic” ring E. Such bacterio-131-oxophorbines have heretofore only been available in the naturally occurring compounds, and analogues bearing six-membered rings have only been available by derivatization of bacteriochlorophylls. A de novo route to synthetic bacteriochlorins, which bear a geminal dimethyl group in each pyrroline ring, has been extended to gain access to a bacterio-131-oxophorbine and bacteriochlorin-13,15-dicarboximides. The route relies on acid-catalyzed condensation of a dihydrodipyrrin-acetal to form the bacteriochlorin, which then is subjected to regioselective 15-bromination. Pd-mediated cyclization of the 15-bromobacteriochlorin bearing a 13-acetylgroup (intramolecular α-arylation) or 13-ethoxycarbonylgroup (carbamoylation and intramolecular imidation) gives the bacterio-131-oxophorbine or bacteriochlorin-13,15-dicarboximide, respectively. The resulting macrocycles exhibit absorption in the near-infrared spectral region (733–818 nm), which extends the spectral coverage beyond that obtained previously with synthetic bacteriochlorins that lack a fifth ring. The macrocycles also exhibit excited singlet-state lifetimes (1.9–4.6 ns) comparable to or longer than those of natural photosynthetic pigments. Density functional theory calculations predict that the bathochromically shifted absorption is primarily due to lowering of the energy of the lowest unoccupied molecular orbital. The new route complements existing semisynthetic routes and should enable fundamental spectroscopic studies and diverse photochemical applications.
Journal of Medicinal Chemistry, 2010
Photodynamic therapy (PDT) is a rapidly developing approach to treating cancer that combines harm... more Photodynamic therapy (PDT) is a rapidly developing approach to treating cancer that combines harmless visible and near-infrared light with a nontoxic photoactivatable dye, which upon encounter with molecular oxygen generates the reactive oxygen species that are toxic to cancer cells. Bacteriochlorins are tetrapyrrole compounds with two reduced pyrrole rings in the macrocycle. These molecules are characterized by strong absorption features from 700 to >800 nm, which enable deep penetration into tissue. This report describes testing of 12 new stable synthetic bacteriochlorins for PDT activity. The 12 compounds possess a variety of peripheral substituents and are very potent in killing cancer cells in vitro after illumination. Quantitative structure-activity relationships were derived, and subcellular localization was determined. The most active compounds have both low dark toxicity and high phototoxicity. This combination together with near-infrared absorption gives these bacteriochlorins great potential as photosensitizers for treatment of cancer.
ChemMedChem, 2012
Photodynamic therapy (PDT) is a rapidly developing cancer therapy that utilizes the combination o... more Photodynamic therapy (PDT) is a rapidly developing cancer therapy that utilizes the combination of a nontoxic dye, termed a photosensitizer (PS), and harmless visible or near-infrared (NIR) light to kill cancer cells and destroy tumors by generating reactive oxygen species (ROS), such as singlet oxygen, superoxide and hydroxyl radical. PDT has the advantage of dual selectivity in that the PS can be targeted to its destination cell or tissue and the illumination can be spatially directed to the lesion. The ROS produced during PDT are effective in killing both malignant and normal cells via necrosis, apoptosis or autophagy, depending on the cell type, structure of the PS, and the light parameters chosen.