Ruffling in a Series of Nickel(II) meso-Tetrasubstituted Porphyrins as a Model for the Conserved Ruffling of the Heme of Cytochromes c

Jentzen, Walter; Simpson, M. Cather; Hobbs, J.; Song, Xing-Zhi; Ema, Tadashi; Nelson, Nora Y.; Medforth, Craig J.; Smith, Kevin M.; Veyrat, Marc; Mazzanti, Marinella; Ramasseul, R.; Marchon, Jean‐Claude; Takeuchi, Toshihiko; Goddard, William A.; Shelnutt, John A.

doi:10.1021/ja00150a008

Cited by 292 publications

(505 citation statements)

References 58 publications

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“…The two pairs of pyrrole rings are twisted in the opposite direction, resulting in a saddle shape for the porphyrin. This type of deviation has been observed in the crystal structures of a number of substituted metalloporphyrins (23)(24)(25)(26). The distortions are most likely to be a consequence of the short Ni-N(pyrrole) distances ( here to assume a planar conformation.…”

Section: Resultsmentioning

confidence: 75%

A DNA–porphyrin minor-groove complex at atomic resolution: The structural consequences of porphyrin ruffling

Bennett

Krah

Wien

et al. 2000

Proc. Natl. Acad. Sci. U.S.A.

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The crystal structure of a B-type DNA hexanucleotide duplex complexed with the porphyrin molecule nickel-[tetra-N-methylpyridyl] porphyrin has been solved by multiwavelength anomalous diffraction phasing and refined to an R factor of 11.5% at a resolution of 0.9 Å. The structure has been solved and refined as two crystallographically independent duplexes, stacked end to end. Contrary to expectation, the porphyrin molecule is not intercalated into the duplex but is stacked onto the ends of the two-duplex stack. The porphyrin molecule is highly buckled as a consequence of the nickel coordination, which produces large changes in local DNA structure. A second mode of porphyrin binding is apparent as a consequence of crystal packing, which places the ligand in the minor groove of an adjacent duplex. This structure thus provides, to our knowledge, the first atomic visualization of minor-groove binding for a porphyrin molecule. The geometry of groove binding provides a ready explanation for porphyrin-induced DNA strand cleavage at deoxyribose residues.DNA structure ͉ minor groove binding ͉ end capping T he interactions of cationic porphyrins with nucleic acids have received considerable attention (1, 2). Several have clinical potential as anticancer agents in photodynamic therapy (3, 4), probably as a consequence of their ability to selectively accumulate on the surface of tumor cells, become internalized, bind to genomic DNA, and then induce DNA strand cleavage. One such compound is tetra-(N-methylpyridyl) porphyrin (TMPy: Fig. 1a), which can be coordinated with a range of transition metals (1, 2, 5, 6). TMPy has more direct antitumor activity, possibly as a consequence of its ability to inhibit the telomerase enzyme (7). Binding to quadruplex DNA as well as to duplexes has been reported for TMPy and various complexes (8-10). Stabilization of G-quadruplex structures has been shown to be the mechanism whereby TMPy inhibits telomerase from catalyzing the synthesis of further linear telomere repeats. NMR and photocleavage data have been interpreted in favor of a model with a TMPy molecule externally stacking onto guaninequadruplex structures (8-10).Noncovalent interactions of TMPy and its metal complexes with duplex DNA are sequence dependent (2, 11), with intercalation occurring at 5Ј-CpG sites, as shown by NMR and other biophysical studies (12, 13) as well as molecular modeling (13,14). A crystallographic analysis (15) of the Cu 2ϩ complex of TMPy bound to the sequence 5Ј-d(CGTACG) 2 also found the ligand intercalated at this site, but with the 5Ј-end cytosine swung out in an extrahelical arrangement. By contrast, biophysical and modeling (14, 16) studies have suggested that TMPy itself (and many of its metal complexes) bind in the minor groove at A͞T sequences and perturb the double helix only to a minimal extent at such sites (16). No structural data has been reported to date on groove-binding modes. TMPy itself is a planar molecule (14, 15), and it has been assumed that the groove binding would therefore be analogou...

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Section: Resultsmentioning

confidence: 75%

A DNA–porphyrin minor-groove complex at atomic resolution: The structural consequences of porphyrin ruffling

Bennett

Krah

Wien

et al. 2000

Proc. Natl. Acad. Sci. U.S.A.

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“…2). These spectroscopic features are characteristic of a nonplanar porphyrin (16)(17)(18)(19)(20)(21)(22). Steric repulsion between the β-cyano groups and the meso-phenyl substituents leads to deformation of the tetrapyrrolic ring from its original planar geometry.…”

Section: Resultsmentioning

confidence: 99%

Mimicking the electron transfer chain in photosystem II with a molecular triad thermodynamically capable of water oxidation

Megiatto

Antoniuk-Pablant

Sherman

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

112

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In the photosynthetic photosystem II, electrons are transferred from the manganese-containing oxygen evolving complex (OEC) to the oxidized primary electron-donor chlorophyll P680 •+ by a proton-coupled electron transfer process involving a tyrosine-histidine pair. Proton transfer from the tyrosine phenolic group to a histidine nitrogen positions the redox potential of the tyrosine between those of P680 •+ and the OEC. We report the synthesis and time-resolved spectroscopic study of a molecular triad that models this electron transfer. The triad consists of a high-potential porphyrin bearing two pentafluorophenyl groups (PF 10 ), a tetracyanoporphyrin electron acceptor (TCNP), and a benzimidazole-phenol secondary electron-donor (Bi-PhOH). Excitation of PF 10 in benzonitrile is followed by singlet energy transfer to TCNP ( τ = 41 ps), whose excited state decays by photoinduced electron transfer ( τ = 830 ps) to yield . A second electron transfer reaction follows ( τ < 12 ps), giving a final state postulated as BiH + -PhO • -PF 10 -TCNP •- , in which the phenolic proton now resides on benzimidazole. This final state decays with a time constant of 3.8 μs. The triad thus functionally mimics the electron transfers involving the tyrosine-histidine pair in PSII. The final charge-separated state is thermodynamically capable of water oxidation, and its long lifetime suggests the possibility of coupling systems such as this system to water oxidation catalysts for use in artificial photosynthetic fuel production.

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“…52 Calculation of spectroscopic properties of porphyrins using the popular INDO/S method has a well-established precedent in porphyrins and their metal complexes. 32,34,53,54 INDO/S correctly reproduces the non-planarity induced red-shifts of sterically encumbered non-planar porphyrins, providing a realistic geometry is provided (i.e., either from a crystallographic study or suitable in silico optimization). 32,34 Work using geometries obtained from MM optimizations (e.g., a porphyrin specific DRIEDING II) has shown that INDO/S calculations may often systematically overestimate the Q y wavelength, whilst the Soret band is underestimated, but crucially relative differences amongst compounds are very well modelled.…”

Section: Methodsmentioning

confidence: 94%

“…32,34 Work using geometries obtained from MM optimizations (e.g., a porphyrin specific DRIEDING II) has shown that INDO/S calculations may often systematically overestimate the Q y wavelength, whilst the Soret band is underestimated, but crucially relative differences amongst compounds are very well modelled. 32,54 Linnanto and Korppi-Tommola 55,56,57 have performed extensive comparisons of the accuracy of semi-empirical and ab initio methods for the calculation of geometries and excitation energies of chlorophylls and bacteriochlorophylls. These studies have ranged from isolated molecules and solvent complexes all the way to full models of reaction center and light-harvesting complexes.…”

Section: Methodsmentioning

confidence: 99%

Conformational control of cofactors in nature – the influence of protein-induced macrocycle distortion on the biological function of tetrapyrroles

2015

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Tetrapyrrole-containing proteins are one of the most fundamental classes of enzymes in nature and it remains an open question to give a chemical rationale for the multitude of biological reactions that can be catalyzed by these pigmentprotein complexes. There are many fundamental processes where the same (i.e., chemically identical) porphyrin cofactor is involved in chemically quite distinct reactions. For example, heme is the active cofactor for oxygen transport and storage (hemoglobin, myoglobin) and for the incorporation of molecular oxygen in organic substrates (cytochrome P 450 ). It is involved in the terminal oxidation (cytochrome c oxidase) and the metabolism of H 2 O 2 (catalases and peroxidases) and catalyzes various electron transfer reactions in cytochromes. Likewise, in photosynthesis the same chlorophyll cofactor may function as a reaction center pigment (charge separation) or as an accessory pigment (exciton transfer) in light harvesting complexes (e.g., chlorophyll a). Whilst differences in the apoprotein sequences alone cannot explain the often drastic differences in physicochemical properties encountered for the same cofactor in diverse protein complexes, a critical factor for all biological functions must be the close structural interplay between bound cofactors and the respective apoprotein in addition to factors such as hydrogen bonding or electronic effects. Here, we explore how nature can use the same chemical molecule as a cofactor for chemically distinct reactions using the concept of conformational flexibility of tetrapyrroles. The multifaceted roles of tetrapyrroles are discussed in the context of the current knowledge on distorted porphyrins. Contemporary analytical methods now allow a more quantitative look at cofactors in protein complexes and the development of the field is illustrated by case studies on hemeproteins and photosynthetic complexes. Specific tetrapyrrole conformations are now used to prepare bioengineered designer proteins with specific catalytic or photochemical properties.

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Ruffling in a Series of Nickel(II) meso-Tetrasubstituted Porphyrins as a Model for the Conserved Ruffling of the Heme of Cytochromes c

Cited by 292 publications

References 58 publications

A DNA–porphyrin minor-groove complex at atomic resolution: The structural consequences of porphyrin ruffling

A DNA–porphyrin minor-groove complex at atomic resolution: The structural consequences of porphyrin ruffling

Mimicking the electron transfer chain in photosystem II with a molecular triad thermodynamically capable of water oxidation

Conformational control of cofactors in nature – the influence of protein-induced macrocycle distortion on the biological function of tetrapyrroles

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