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Pradip K Mascharak - One of the best experts on this subject based on the ideXlab platform.
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Recent Progress in Photoinduced NO Delivery With Designed Ruthenium Nitrosyl Complexes
NOx Related Chemistry, 2015Co-Authors: Tara R. Deboer, Pradip K MascharakAbstract:Abstract This chapter focuses on our recent work in the area of designed ruthenium nitrosyl complexes and their potential as NO donors to biological targets. Special attention has been given to the design strategies that afford Nitrosyls capable of releasing NO upon exposure to visible light of various wavelengths. Results of theoretical studies have been utilized to gain insight into their photophysical properties and mechanism(s) of NO photodissociation. Techniques of sensitizing the otherwise UV-sensitive ruthenium Nitrosyls to visible light by attachment of light-harvesting dye molecules have also been discussed.
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evidence of dexter energy transfer in no photolability of dye sensitized ruthenium Nitrosyls
Inorganica Chimica Acta, 2013Co-Authors: Tara R Deboermaggard, Nicole L Fry, Pradip K MascharakAbstract:Abstract Direct attachment of light-harvesting dye molecules to the ruthenium center of designed {Ru–NO}6 Nitrosyls has been shown to exhibit enhanced light-induced NO photorelease upon exposure to visible light. Theoretical studies have indicated that orbital overlap between the MOs of the dye and the nitrosyl units are key for such sensitization. In order to check whether altering the electronic conjugation between these two units causes reduction in the extent of sensitization, we have synthesized a pyridinyloxy-fluorescein dye PyFlEt and attached it to two designed ruthenium Nitrosyls through the pyridine-N donor of the pyridinyloxy-end. The quantum yield values of NO photodissociation at 500 nm (ϕNO) and fluorescence quantum yield values (ϕFl) of these two nitrosyl–dye conjugates namely, [(Me)2bpb)Ru(NO)(PyFlEt)]ClO4 (1-PyFlEt) and [((OMe)2IQ1)Ru(NO)(PyFlEt)]BF4 (2-PyFlEt) have been compared with those of [(Me)2bpb)Ru(NO)(FlEt)]ClO4 (1-FlEt) and [((OMe)2IQ1)Ru(NO)(FlEt)]BF4 (2-FlEt) in which the same FlEt dye is directly attached through the phenolato-O donor. This minor alteration in the linkage between the dye and the nitrosyl unit has caused significant reduction in the ϕNO values of 1-PyFlEt and 2-PyFlEt while their ϕFl values have shown moderate improvement. These results strongly suggest that the light energy absorbed by the dye unit is transferred to the Ru–NO moiety through the Dexter pathway. If the electronic overlap is disrupted, only part of the energy is used in NO photorelease and a significant portion is lost through fluorescence.
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photolability of no in designed metal Nitrosyls with carboxamido n donors a theoretical attempt to unravel the mechanism
Dalton Transactions, 2012Co-Authors: Nicole L Fry, Pradip K MascharakAbstract:During the past few years, photoactive metal Nitrosyls (NO complexes of metals) have drawn attention as potential drugs for delivery of nitric oxide (NO) to biological targets under the control of light. Major success in this area has been achieved with designed metal Nitrosyls derived from ligands that contain carboxamide group(s). A number of iron, manganese and ruthenium {MNO}6 Nitrosyls of such kind exhibit excellent NO photolability under low-power visible and near-IR light. The results of theoretical studies on these NO-donors have provided insight into (a) the electronic transitions that lead to photorelease of NO and (b) the structural features of the ligands that dictate the sensitivity of the Nitrosyls to light of specific wavelengths. In addition, the results have afforded clear understanding of the electronic configurations of the various Nitrosyls. This article highlights these results in a coherent manner. Good matches between the predicted and observed spectral features and NO photolability strongly suggest that theoretical studies should be an integral part of the smart design of such NO-donors in the future research.
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dye tethered ruthenium Nitrosyls containing planar dicarboxamide tetradentate n4 ligands effects of in plane ligand twist on no photolability
Inorganic Chemistry, 2011Co-Authors: Nicole L Fry, Brandon J Heilman, Pradip K MascharakAbstract:To examine the steric effects of the in-plane ligands in dye-sensitized {RuNO}(6) Nitrosyls on their NO photolability, two new ligands, namely, 1,2-Bis(pyridine-2-carboxamido)-4,5-dimethoxybenzene (H(2)(OMe)(2)bpb) and 1,2-Bis(Isoquinoline-1-carboxamido)-4,5-dimethoxybenzene (H(2)(OMe)(2)IQ1, H's are dissociable carboxamide protons) have been designed and synthesized. The syntheses and spectroscopic properties of {RuNO}(6) Nitrosyls derived from these two ligands, namely, [((OMe)(2)bpb)Ru(NO)(Cl)] (4-Cl), [((OMe)(2)IQ1)Ru(NO)(Cl)] (5-Cl), [((OMe)(2)bpb)Ru(NO)(Resf)] (4-Resf), and [((OMe)(2)IQ1)Ru(NO)(Resf)] (5-Resf), are reported. The structures of 5-Cl, 4-Resf, and 5-Resf have been determined by X-ray crystallography. Removal of the in-plane ligand twist in the quinoline-based R(2)bQb(2-) ligand frame (because of steric interactions between the extended quinoline ring systems) in both R(2)bpb(2-) and R(2)IQ1(2-) (pyridine and 1-isoquinoline rings, respectively, instead of quinoline rings in the equatorial plane) results in enhanced solution stability, as well as higher quantum yield values for NO photorelease upon exposure to 500 nm light. Both dye-tethered {RuNO}(6) Nitrosyls 4-Resf and 5-Resf exhibit greater sensitivity to visible light compared to the chloro-bound species 4-Cl and 5-Cl. In addition, the dye-tethered Nitrosyls are fluorescent and hence can be used as trackable NO donors in cellular studies.
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ruthenium Nitrosyls derived from tetradentate ligands containing carboxamido n and phenolato o donors syntheses structures photolability and time dependent density functional theory studies
Inorganic Chemistry, 2010Co-Authors: Nicole L Fry, Michael J Rose, David L Rogow, Crystal Nyitray, Manpreet Kaur, Pradip K MascharakAbstract:In order to examine the role(s) of designed ligands on the NO photolability of {Ru-NO}6 Nitrosyls, a set of three Nitrosyls with ligands containing two carboxamide groups along with a varying number of phenolates have been synthesized. The Nitrosyls namely, (NEt4)2[(hybeb)Ru(NO)(OEt)] (1), (PPh4)[(hypyb)Ru(NO)(OEt)] (2), and [(bpb)Ru(NO)(OEt)] (3) have been characterized by X-ray crystallography. Complexes 1−3 are diamagnetic, exhibit νNO in the range 1780−1840 cm−1 and rapidly release NO in solution upon exposure to low power UV light (7 mW/cm2). Density Functional Theory (DFT) and Time Dependent DFT (TDDFT) calculations on 1−3 indicate considerable contribution of ligand orbitals in the MOs involved in transitions leading to NO photolability. The results of the theoretical studies match well with the experimental absorption spectra as well as the parameters for NO photorelease and provide insight into the transition(s) associated with loss of NO.
Michael J Rose - One of the best experts on this subject based on the ideXlab platform.
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ruthenium Nitrosyls derived from tetradentate ligands containing carboxamido n and phenolato o donors syntheses structures photolability and time dependent density functional theory studies
Inorganic Chemistry, 2010Co-Authors: Nicole L Fry, Michael J Rose, David L Rogow, Crystal Nyitray, Manpreet Kaur, Pradip K MascharakAbstract:In order to examine the role(s) of designed ligands on the NO photolability of {Ru-NO}6 Nitrosyls, a set of three Nitrosyls with ligands containing two carboxamide groups along with a varying number of phenolates have been synthesized. The Nitrosyls namely, (NEt4)2[(hybeb)Ru(NO)(OEt)] (1), (PPh4)[(hypyb)Ru(NO)(OEt)] (2), and [(bpb)Ru(NO)(OEt)] (3) have been characterized by X-ray crystallography. Complexes 1−3 are diamagnetic, exhibit νNO in the range 1780−1840 cm−1 and rapidly release NO in solution upon exposure to low power UV light (7 mW/cm2). Density Functional Theory (DFT) and Time Dependent DFT (TDDFT) calculations on 1−3 indicate considerable contribution of ligand orbitals in the MOs involved in transitions leading to NO photolability. The results of the theoretical studies match well with the experimental absorption spectra as well as the parameters for NO photorelease and provide insight into the transition(s) associated with loss of NO.
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photosensitization of ruthenium Nitrosyls to red light with an isoelectronic series of heavy atom chromophores experimental and density functional theory studies on the effects of o s and se substituted coordinated dyes
Inorganic Chemistry, 2009Co-Authors: Michael J Rose, Pradip K MascharakAbstract:Three ruthenium nitrosyl-dye conjugates, namely, [((OMe)2bQb)Ru(NO)(Resf)] (RuNO-Resf), [((OMe)2bQb)Ru(NO)(Thnl)] (RuNO-Thnl), and [((OMe)2bQb)Ru(NO)(Seln)] (RuNO-Seln) have been synthesized using the tetradentate N4 dicarboxamido ligand H2(OMe)2bQb. Each nitrosyl of this series is conjugated to a phenoxazine-type heterotricyclic chromophore which has been systematically varied in a central position to test the effects of “heavy-atom” substitution (O = Resorufin; S = Thionol; Se = Selenophore) in photosensitization. The structure of the chloride-bound precursor {Ru-NO}6 nitrosyl [((OMe)2bQb)Ru(NO)(Cl)] (RuNO-Cl) and three nitrosyl-dye conjugates, namely, RuNO-Resf, RuNO-Thnl and RuNO-Seln, have been determined by X-ray crystallography. All three nitrosyl-dye conjugates exhibit sharp 1H NMR spectra (S = 0 ground state) and νNO stretches in the IR spectrum in the region 1825−1855 cm−1, typical of {Ru-NO}6 Nitrosyls. The presence of a heavy atom in the bound dye gives rise to a systematic red-shift in the el...
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sensitization of ruthenium Nitrosyls to visible light via direct coordination of the dye resorufin trackable no donors for light triggered no delivery to cellular targets
Journal of the American Chemical Society, 2008Co-Authors: Michael J Rose, Nicole L Fry, Rebecca Marlow, Lindsay Hinck, Pradip K MascharakAbstract:Three nitrosyl-dye conjugates, namely, [(Me 2bpb)Ru(NO)(Resf)] ( 1-Resf), [(Me 2bQb)Ru(NO)(Resf)] ( 2-Resf), and [((OMe) 2bQb)Ru(NO)(Resf)] ( 3-Resf) have been synthesized via direct replacement of the chloride ligand of the parent {Ru-NO} (6) Nitrosyls of the type [(R 2byb)Ru(NO)(L)] with the anionic tricyclic dye resorufin (Resf). The structures of 1-Resf- 3-Resf have been determined by X-ray crystallography. The dye is coordinated to the ruthenium centers of these conjugates via the phenolato-O atom and is trans to NO. Systematic red shift of the d pi(Ru) --> pi*(NO) transition of the parent Nitrosyls [(R 2byb)Ru(NO)(L)] due to changes in R and y in the equatorial tetradentate ligand R 2byb (2-) results in its eventual merge with the intense absorption band of the dye around 500 nm in 3-Resf. Unlike the UV-sensitive parent [(R 2byb)Ru(NO)(L)] Nitrosyls, these dye-sensitized Nitrosyls rapidly release NO when exposed to visible light (lambda >/= 465 nm). Comparison of the photochemical parameters reveals that direct coordination of the light-harvesting chromophore to the ruthenium center in the present Nitrosyls results in a significantly greater extent of sensitization to visible light compared to Nitrosyls with appended chromophore (linked via alkyl chains). 1-Resf has been employed as a "trackable" NO donor to promote NO-induced apoptosis in MDA-MB-231 human breast cancer cells under the control of light. The results of this work demonstrate that (a) the d pi(Ru) --> pi*(NO) transition (photoband) of {Ru-NO} (6) Nitrosyls can be tuned into visible range via careful alteration of the ligand frame(s) and (b) such Nitrosyls can be significantly sensitized to visible light by directly ligating a light-harvesting chromophore to the ruthenium center. The potential of these photosensitive nitrosyl-dye conjugates as (i) biological tools to study the effects of NO in cellular environments and (ii) "trackable" NO donors in photodynamic therapy of malignancies (such as skin cancer) has been discussed.
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fiat lux selective delivery of high flux of nitric oxide no to biological targets using photoactive metal Nitrosyls
Current Opinion in Chemical Biology, 2008Co-Authors: Michael J Rose, Pradip K MascharakAbstract:In addition to its beneficial roles in blood pressure regulation, immune response, neurotransmission, and redox balance, nitric oxide (NO) can induce cellular apoptosis at relatively high concentrations. Since photoactive metal Nitrosyls can deliver NO under the control of light, they are uniquely suited as NO drugs in photodynamic therapy (PDT) to destroy cancer cells. Stable and photoactive metal Nitrosyls can first be placed in close proximity of a malignant site and then triggered via pulses of light to deliver high flux of NO. During the past few years, a number of such metal-based 'NO carriers' have been synthesized and tuned for rapid release of NO upon exposure to UV or visible light. Using various chromophore conjugation strategies, attempts are now being made to photosensitize the M-NO bond to infrared light. Progress has also been made in incorporating metal Nitrosyls into biocompatible matrices for site-specific delivery of NO to tumors. A combination of light and NO could offer a viable treatment modality for cancer.
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Photoactive Ruthenium Nitrosyls: Effects of Light and Potential Application as NO Donors.
Coordination Chemistry Reviews, 2007Co-Authors: Michael J Rose, Pradip K MascharakAbstract:Abstract In recent years, various exogenous nitric oxide (NO) donors have been synthesized to modulate NO concentrations in cellular environments and control physiological processes that are regulated by NO. Transition metal complexes of NO (metal Nitrosyls) are one such class of NO donors. Since complexes of ruthenium are in general more stable, a variety of ruthenium Nitrosyls have been isolated and studied in detail in terms of their NO donating capacities. A large number of {Ru–NO} 6 type of Nitrosyls release NO upon exposure to UV light. Several research groups have studied their photochemistry to evaluate their potential as NO donors under the control of light. In general, the Nitrosyls with non-porphyrin ligands (such as amines, Schiff bases, thiolates and ligands with carboxamide groups) readily release NO upon illumination and generate Ru(III) photoproducts. In contrast, NO photorelease from ruthenium Nitrosyls derived from porphyrins remains limited due to rapid recombination. In some cases, the {Ru–NO} 6 Nitrosyls are photochemically converted to nitrite species (especially in water at neutral pH) while a few afford Ru(II) photoproducts. UV irradiation of selected ruthenium Nitrosyls in the solid state results in NO linkage isomerism. To date, notable progress has been made in the area of nitrosyl-polymer hybrids that could be used for site-specific delivery of NO. Various strategies have also been developed to make these Nitrosyls release NO under the influence of visible and/or near IR light. Although some ruthenium Nitrosyls are stable under physiological conditions and are capable to NO delivery to proteins such as myoglobin and cytochrome c oxidase, so far success has been limited in using these Nitrosyls as light-activated NO donors in cellular and tissue models. In this review, the effects of light on ruthenium Nitrosyls derived from a wide variety of ligands (reported so far) have been summarized and their utility as NO donors have been discussed.
Nicole L Fry - One of the best experts on this subject based on the ideXlab platform.
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evidence of dexter energy transfer in no photolability of dye sensitized ruthenium Nitrosyls
Inorganica Chimica Acta, 2013Co-Authors: Tara R Deboermaggard, Nicole L Fry, Pradip K MascharakAbstract:Abstract Direct attachment of light-harvesting dye molecules to the ruthenium center of designed {Ru–NO}6 Nitrosyls has been shown to exhibit enhanced light-induced NO photorelease upon exposure to visible light. Theoretical studies have indicated that orbital overlap between the MOs of the dye and the nitrosyl units are key for such sensitization. In order to check whether altering the electronic conjugation between these two units causes reduction in the extent of sensitization, we have synthesized a pyridinyloxy-fluorescein dye PyFlEt and attached it to two designed ruthenium Nitrosyls through the pyridine-N donor of the pyridinyloxy-end. The quantum yield values of NO photodissociation at 500 nm (ϕNO) and fluorescence quantum yield values (ϕFl) of these two nitrosyl–dye conjugates namely, [(Me)2bpb)Ru(NO)(PyFlEt)]ClO4 (1-PyFlEt) and [((OMe)2IQ1)Ru(NO)(PyFlEt)]BF4 (2-PyFlEt) have been compared with those of [(Me)2bpb)Ru(NO)(FlEt)]ClO4 (1-FlEt) and [((OMe)2IQ1)Ru(NO)(FlEt)]BF4 (2-FlEt) in which the same FlEt dye is directly attached through the phenolato-O donor. This minor alteration in the linkage between the dye and the nitrosyl unit has caused significant reduction in the ϕNO values of 1-PyFlEt and 2-PyFlEt while their ϕFl values have shown moderate improvement. These results strongly suggest that the light energy absorbed by the dye unit is transferred to the Ru–NO moiety through the Dexter pathway. If the electronic overlap is disrupted, only part of the energy is used in NO photorelease and a significant portion is lost through fluorescence.
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photolability of no in designed metal Nitrosyls with carboxamido n donors a theoretical attempt to unravel the mechanism
Dalton Transactions, 2012Co-Authors: Nicole L Fry, Pradip K MascharakAbstract:During the past few years, photoactive metal Nitrosyls (NO complexes of metals) have drawn attention as potential drugs for delivery of nitric oxide (NO) to biological targets under the control of light. Major success in this area has been achieved with designed metal Nitrosyls derived from ligands that contain carboxamide group(s). A number of iron, manganese and ruthenium {MNO}6 Nitrosyls of such kind exhibit excellent NO photolability under low-power visible and near-IR light. The results of theoretical studies on these NO-donors have provided insight into (a) the electronic transitions that lead to photorelease of NO and (b) the structural features of the ligands that dictate the sensitivity of the Nitrosyls to light of specific wavelengths. In addition, the results have afforded clear understanding of the electronic configurations of the various Nitrosyls. This article highlights these results in a coherent manner. Good matches between the predicted and observed spectral features and NO photolability strongly suggest that theoretical studies should be an integral part of the smart design of such NO-donors in the future research.
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dye tethered ruthenium Nitrosyls containing planar dicarboxamide tetradentate n4 ligands effects of in plane ligand twist on no photolability
Inorganic Chemistry, 2011Co-Authors: Nicole L Fry, Brandon J Heilman, Pradip K MascharakAbstract:To examine the steric effects of the in-plane ligands in dye-sensitized {RuNO}(6) Nitrosyls on their NO photolability, two new ligands, namely, 1,2-Bis(pyridine-2-carboxamido)-4,5-dimethoxybenzene (H(2)(OMe)(2)bpb) and 1,2-Bis(Isoquinoline-1-carboxamido)-4,5-dimethoxybenzene (H(2)(OMe)(2)IQ1, H's are dissociable carboxamide protons) have been designed and synthesized. The syntheses and spectroscopic properties of {RuNO}(6) Nitrosyls derived from these two ligands, namely, [((OMe)(2)bpb)Ru(NO)(Cl)] (4-Cl), [((OMe)(2)IQ1)Ru(NO)(Cl)] (5-Cl), [((OMe)(2)bpb)Ru(NO)(Resf)] (4-Resf), and [((OMe)(2)IQ1)Ru(NO)(Resf)] (5-Resf), are reported. The structures of 5-Cl, 4-Resf, and 5-Resf have been determined by X-ray crystallography. Removal of the in-plane ligand twist in the quinoline-based R(2)bQb(2-) ligand frame (because of steric interactions between the extended quinoline ring systems) in both R(2)bpb(2-) and R(2)IQ1(2-) (pyridine and 1-isoquinoline rings, respectively, instead of quinoline rings in the equatorial plane) results in enhanced solution stability, as well as higher quantum yield values for NO photorelease upon exposure to 500 nm light. Both dye-tethered {RuNO}(6) Nitrosyls 4-Resf and 5-Resf exhibit greater sensitivity to visible light compared to the chloro-bound species 4-Cl and 5-Cl. In addition, the dye-tethered Nitrosyls are fluorescent and hence can be used as trackable NO donors in cellular studies.
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ruthenium Nitrosyls derived from tetradentate ligands containing carboxamido n and phenolato o donors syntheses structures photolability and time dependent density functional theory studies
Inorganic Chemistry, 2010Co-Authors: Nicole L Fry, Michael J Rose, David L Rogow, Crystal Nyitray, Manpreet Kaur, Pradip K MascharakAbstract:In order to examine the role(s) of designed ligands on the NO photolability of {Ru-NO}6 Nitrosyls, a set of three Nitrosyls with ligands containing two carboxamide groups along with a varying number of phenolates have been synthesized. The Nitrosyls namely, (NEt4)2[(hybeb)Ru(NO)(OEt)] (1), (PPh4)[(hypyb)Ru(NO)(OEt)] (2), and [(bpb)Ru(NO)(OEt)] (3) have been characterized by X-ray crystallography. Complexes 1−3 are diamagnetic, exhibit νNO in the range 1780−1840 cm−1 and rapidly release NO in solution upon exposure to low power UV light (7 mW/cm2). Density Functional Theory (DFT) and Time Dependent DFT (TDDFT) calculations on 1−3 indicate considerable contribution of ligand orbitals in the MOs involved in transitions leading to NO photolability. The results of the theoretical studies match well with the experimental absorption spectra as well as the parameters for NO photorelease and provide insight into the transition(s) associated with loss of NO.
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sensitization of ruthenium Nitrosyls to visible light via direct coordination of the dye resorufin trackable no donors for light triggered no delivery to cellular targets
Journal of the American Chemical Society, 2008Co-Authors: Michael J Rose, Nicole L Fry, Rebecca Marlow, Lindsay Hinck, Pradip K MascharakAbstract:Three nitrosyl-dye conjugates, namely, [(Me 2bpb)Ru(NO)(Resf)] ( 1-Resf), [(Me 2bQb)Ru(NO)(Resf)] ( 2-Resf), and [((OMe) 2bQb)Ru(NO)(Resf)] ( 3-Resf) have been synthesized via direct replacement of the chloride ligand of the parent {Ru-NO} (6) Nitrosyls of the type [(R 2byb)Ru(NO)(L)] with the anionic tricyclic dye resorufin (Resf). The structures of 1-Resf- 3-Resf have been determined by X-ray crystallography. The dye is coordinated to the ruthenium centers of these conjugates via the phenolato-O atom and is trans to NO. Systematic red shift of the d pi(Ru) --> pi*(NO) transition of the parent Nitrosyls [(R 2byb)Ru(NO)(L)] due to changes in R and y in the equatorial tetradentate ligand R 2byb (2-) results in its eventual merge with the intense absorption band of the dye around 500 nm in 3-Resf. Unlike the UV-sensitive parent [(R 2byb)Ru(NO)(L)] Nitrosyls, these dye-sensitized Nitrosyls rapidly release NO when exposed to visible light (lambda >/= 465 nm). Comparison of the photochemical parameters reveals that direct coordination of the light-harvesting chromophore to the ruthenium center in the present Nitrosyls results in a significantly greater extent of sensitization to visible light compared to Nitrosyls with appended chromophore (linked via alkyl chains). 1-Resf has been employed as a "trackable" NO donor to promote NO-induced apoptosis in MDA-MB-231 human breast cancer cells under the control of light. The results of this work demonstrate that (a) the d pi(Ru) --> pi*(NO) transition (photoband) of {Ru-NO} (6) Nitrosyls can be tuned into visible range via careful alteration of the ligand frame(s) and (b) such Nitrosyls can be significantly sensitized to visible light by directly ligating a light-harvesting chromophore to the ruthenium center. The potential of these photosensitive nitrosyl-dye conjugates as (i) biological tools to study the effects of NO in cellular environments and (ii) "trackable" NO donors in photodynamic therapy of malignancies (such as skin cancer) has been discussed.
Nicolai Lehnert - One of the best experts on this subject based on the ideXlab platform.
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Non-heme High-Spin {FeNO}6–8 Complexes: One Ligand Platform Can Do It All
2018Co-Authors: Amy L. Speelman, Bo Zhang, Corey J. White, Ercan E. Alp, Jiyong Zhao, Carsten Krebs, James Penner-hahn, Nicolai LehnertAbstract:Heme and non-heme iron–nitrosyl complexes are important intermediates in biology. While there are numerous examples of low-spin heme iron–nitrosyl complexes in different oxidation states, much less is known about high-spin (hs) non-heme iron–Nitrosyls in oxidation states other than the formally ferrous NO adducts ({FeNO}7 in the Enemark–Feltham notation). In this study, we present a complete series of hs-{FeNO}6–8 complexes using the TMG3tren coligand. Redox transformations from the hs-{FeNO}7 complex [Fe(TMG3tren)(NO)]2+ to its {FeNO}6 and {FeNO}8 analogs do not alter the coordination environment of the iron center, allowing for detailed comparisons between these species. Here, we present new MCD, NRVS, XANES/EXAFS, and Mössbauer data, demonstrating that these redox transformations are metal based, which allows us to access hs-Fe(II)–NO–, Fe(III)–NO–, and Fe(IV)–NO– complexes. Vibrational data, analyzed by NCA, directly quantify changes in Fe–NO bonding along this series. Optical data allow for the identification of a “spectator” charge-transfer transition that, together with Mössbauer and XAS data, directly monitors the electronic changes of the Fe center. Using EXAFS, we are also able to provide structural data for all complexes. The magnetic properties of the complexes are further analyzed (from magnetic Mössbauer). The properties of our hs-{FeNO}6–8 complexes are then contrasted to corresponding, low-spin iron–nitrosyl complexes where redox transformations are generally NO centered. The hs-{FeNO}8 complex can further be protonated by weak acids, and the product of this reaction is characterized. Taken together, these results provide unprecedented insight into the properties of biologically relevant non-heme iron–nitrosyl complexes in three relevant oxidation states
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Heme-Nitrosyls: electronic structure implications for function in biology.
Accounts of chemical research, 2015Co-Authors: Andrew P. Hunt, Nicolai LehnertAbstract:ConspectusThe question of why mammalian systems use nitric oxide (NO), a potentially hazardous and toxic diatomic, as a signaling molecule to mediate important functions such as vasodilation (blood pressure control) and nerve signal transduction initially perplexed researchers when this discovery was made in the 1980s. Through extensive research over the past two decades, it is now well rationalized why NO is used in vivo for these signaling functions, and that heme proteins play a dominant role in NO signaling in mammals. Key insight into the properties of heme-nitrosyl complexes that make heme proteins so well poised to take full advantage of the unique properties of NO has come from in-depth structural, spectroscopic, and theoretical studies on ferrous and ferric heme-Nitrosyls. This Account highlights recent findings that have led to greater understanding of the electronic structures of heme-Nitrosyls, and the contributions that model complex studies have made to elucidate Fe–NO bonding are highlighte...
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Model complexes of key intermediates in fungal cytochrome P450 nitric oxide reductase (P450nor).
Current opinion in chemical biology, 2014Co-Authors: Ashley B. Mcquarters, Nathaniel E Wirgau, Nicolai LehnertAbstract:Denitrifying bacteria and fungi efficiently detoxify the toxic metabolite nitric oxide (NO) through reduction to nitrous oxide (N2O) using nitric oxide reductase (NOR) enzymes. In fungi, for example Fusarium oxysporum, NO is reduced by a Cytochrome P450 NOR (P450nor). This enzyme contains a heme b center coordinated to a proximal cysteinate ligand in the active site. In the proposed mechanism of P450nor, the ferric heme binds NO first to form a ferric heme-nitrosyl complex, which is subsequently reduced by NAD(P)H to generate a ferrous HNO species as the next key intermediate. Recently, key progress has been made in our understanding of the electronic structures and fundamental reactivity of these important intermediates, using suitable model complexes. In this review, model complexes of ferric heme-Nitrosyls with varied axial anionic ligands (such as N-donors, O-donors, and S-donors) are discussed first. Then, the generation and reactivity of ferrous heme-HNO complexes is summarized and related back to the mechanism of P450nor.
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A detailed investigation into the electronic structures of macrocyclic iron(II)-nitrosyl compounds and their similarities to ferrous heme-Nitrosyls
Inorganica Chimica Acta, 2012Co-Authors: Corinne D. Sulok, Jonathan L. Bauer, Amy L. Speelman, Birgit Weber, Nicolai LehnertAbstract:Abstract This paper presents vibrational (IR and FT-Raman) and electronic (UV–Vis absorption and magnetic circular dichroism (MCD)) spectra of the five-coordinate (5C) low-spin ferrous iron-nitrosyl model complexes [Fe(L1)(NO)] (1), [Fe(L2)(NO)], (2) and [Fe(L3)(NO)] (3) that contain Schiff base type tetradentate macrocyclic ligands. These complexes show structural and vibrational data that are very similar to corresponding 5C ferrous heme-Nitrosyls. For example, complexes 1–3 exhibit N–O and Fe–NO stretching frequencies of 1630–1680 and 520–595 cm−1, respectively, which compares well with ν(N–O) and ν(Fe–NO) of [Fe(TPP)(NO)] at 1697 and 532 cm−1. In complexes 1–3, a strong Fe–NO σ bond, mediated by the singly-occupied π∗ orbital of NO and d z 2 of iron, and a medium strong Fe–NO π backbond are present. This is again in close agreement with the electronic structures of 5C ferrous heme-Nitrosyls. Interestingly, a stepwise increase in the strength of the Fe–NO σ bond is observed in the order 1
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electronic structure of heme Nitrosyls and its significance for nitric oxide reactivity sensing transport and toxicity in biological systems
Inorganic Chemistry, 2010Co-Authors: Lauren E Goodrich, Florian Paulat, V K K Praneeth, Nicolai LehnertAbstract:This review summarizes recent developments in the investigation of the electronic structures, spectroscopic properties, and reactivities of ferrous and ferric heme-Nitrosyls and how this relates to important biological processes. Ferrous heme-Nitrosyls show interesting variations in electronic structure as a function of the different types of proximal ligands, as is evident from electron paramagnetic resonance, magnetic circular dichroism, and vibrational spectroscopy. In particular, coordination of imidazoles like histidine (His) increases the radical character on NO and, in this way, could help activate the bound NO for catalysis. Vice versa, the bound NO ligand imposes a strong σ trans effect on the proximal His, which, in the case of soluble guanylate cyclase (sGC), the biological NO sensor protein, induces breaking of the FeII−His bond and activates the protein. The possibility of sGC activation by HNO is also discussed. Finally, the properties of ferrous heme-Nitrosyls with proximal cysteinate (Cys)...
Anthony R. Butler - One of the best experts on this subject based on the ideXlab platform.
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Metal–Nitrosyl complexes as a source of new vasodilators: Strategies derived from systematic chemistry and nitrosyl ligand reactivity
Applied Organometallic Chemistry, 1994Co-Authors: John Reglinski, Anthony R. Butler, Christopher GlidewellAbstract:A series of nitrosyl complexes of empirical formula Kn[M(CN)5NO], where M = V, Cr, Mn and Co and n = 3, or M = Mo and n = 4, have been prepared which are notional analogues of the widely used vasodilator sodium nitroprusside. Their reactivity towards common nucleophiles (OH−, NH2R, NHR2, HS− and RS−), acid and photolysis has been investigated to elucidate the desired properties required of new metal Nitrosyls which may have some potential as new non-cyanide-based vasodilators.
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iron sulphur cluster Nitrosyls a novel class of nitric oxide generator mechanism of vasodilator action on rat isolated tail artery
British Journal of Pharmacology, 1992Co-Authors: Frederick W Flitney, Ian L Megson, D E Flitney, Anthony R. ButlerAbstract:1. Two iron-sulphur cluster Nitrosyls have been investigated as potential nitric oxide (NO.) donor drugs (A: tetranitrosyltetra-mu 3-sulphidotetrahedro-tetrairon; and B: heptanitrosyltri-mu 3-thioxotetraferrate(1-)). Both compounds are shown to dilate precontracted, internally-perfused rat tail arteries. 2. Bolus injections (10 microliters) of compound A or B generate two kinds of vasodilator response. Doses below a critical threshold concentration (DT) evoke transient (or T-type) responses, which resemble those seen with conventional nitrovasodilators. Doses > DT produce sustained (or S-type) responses, comprising an initial, rapid drop of pressure, followed by incomplete recovery, resulting in a plateau of reduced tone which can persist for several hours. 3. T- and S-type responses are attenuated by ferrohaemoglobin (Hb) and by methylene blue (MB), but not by inhibitors of endothelial NO. synthase. Addition of either Hb or MB to the internal perfusate can restore agonist-induced tone when administered during the plateau phase of an S-type response. Moreover, subsequent removal of Hb causes the artery to re-dilate fully. 4. We conclude that T- and S-type responses are both mediated by NO.. It is postulated that S-type responses represent the sum of two vasodilator components: a reversible component, superimposed upon a non-recoverable component. The former is attributed to free NO., preformed in solution at the time of injection; and the latter to NO. generated by gradual decomposition of a 'store' of iron-sulphur-nitrosyl complexes within the tissue. This hypothesis is supported by histochemical studies which show that both clusters accumulate in endothelial cells.