Experimentally calibrated computational chemistry of tryptophan hydroxylase: Trans influence, hydrogen-bonding, and 18-electron rule govern O2-activation

Density functional theory (DFT) calculations are presented on biomimetic model complexes of cysteine dioxygenase and focus on the effect of axial and equatorial ligand placement. Recent studies of one of us [Y. M. Badiei, M. A. Siegler and D. P. Goldberg, J. Am. Chem. Soc. 2011, 133, 1274] gave evidence of a nonheme iron biomimetic model of cysteine dioxygenase using an i-propyl-bis(imino)pyridine, equatorial tridentate ligand. Addition of thiophenol, an anion – either chloride or triflate – and molecular oxygen, led to several possible stereoisomers of this cysteine dioxygenase biomimetic. Moreover, large differences in reactivity using chloride as compared to triflate as the binding anion were observed. Here we present a series of DFT calculations on the origin of these reactivity differences and show that it is caused by the preference of coordination site of anion versus thiophenol binding to the chemical system. Thus, stereochemical interactions of triflate and the bulky iso-propyl substituents of the ligand prevent binding of thiophenol in the trans position using triflate. By contrast, smaller anions, such as chloride, can bind in several ligand positions and give isomers with similar stability. Our calculations explain the observance of thiophenol dioxygenation by this biomimetic system and give details of the reactivity differences of ligated chloride versus triflate.

show abstract

“…The orbital occupation is in line with previous experimental and computational studies of six-coordinate iron(III)-superoxo complexes. 30,33,34 …”

Section: Resultsmentioning

confidence: 99%

Axial and equatorial ligand effects on biomimetic cysteine dioxygenase model complexes

et al. 2012

View full text Add to dashboard Cite

show abstract

“…[114,115] O2 activation [116,117] and the preceding required water dissociation [118] was also investigated in the tetrahydrobiopterin-iron amino acid hydroxylases.…”

Section: Miscellaneous Monoiron Systemsmentioning

confidence: 99%

Mono- and binuclear non-heme iron chemistry from a theoretical perspective

et al. 2016

View full text Add to dashboard Cite

In this minireview, we provide an account of the current state-of-the-art developments in the area of mono-and binuclear non-heme enzymes (NHFe and NHFe2) and the smaller NHFe(2) synthetic models, mostly from a theoretical and computational perspective. The sheer complexity, and at the same time the beauty, of the NHFe(2) world represent a challenge for both experimental as well as theoretical methods. We emphasize that the concerted progress on both theoretical and experimental side is a conditio sine qua non for future understanding, exploration and utilization of the NHFe(2) systems.After briefly discussing the current challenges and advances in the computational methodology, we review the recent spectroscopic and computational studies of NHFe(2) enzymatic and inorganic systems and highlight the correlations between various experimental data (spectroscopic, kinetic, thermodynamic, electrochemical) and computations. Throughout, we attempt to keep in mind the most fascinating and attractive phenomenon in the NHFe(2) chemistry which is the fact that despite the strong oxidative power of many reactive intermediates, the NHFe(2) enzymes perform catalysis with high selectivity. We conclude with our personal viewpoint and hope that further developments in quantum chemistry and especially in the field of multireference wave function methods are needed to have a solid theoretical basis for the NHFe(2) studies, mostly by providing benchmarking and calibration of the computationally efficient and easy-to-use DFT methods.

show abstract

“…30 Our previous combined quantum chemical and Mössbauer spectroscopic investigations have also enabled structure refinement and determination of iron binding sites in a number of iron protein systems. 29, 31-34 Here, we extend such kind of investigation to various first- and second-shell site 1 and site 2 models as well as the experimental Mössbauer properties of Fe-bound EC-Fur.…”

mentioning

confidence: 99%

“…It is well known that 57 Fe Mossbauer spectroscopy is a powerful, sensitive, and direct probe of iron binding sites, and DFT calculations have been successful in investigating Mossbauer properties of nonheme Fe proteins such as soybean monoxygenases, 28 isopenicillin N-synthase, 29 and hydroxy- lase. 30 Our previous combined quantum chemical and Mossbauer spectroscopic investigations have also enabled structure refinement and determination of iron binding sites in a number of iron protein systems. 29,31−34 Here we extend such kind of investigation to various firstand second-shell site 1 and site 2 models as well as the experimental Mossbauer properties of Fe-bound EC-Fur.…”

mentioning

confidence: 99%

Iron Binding Site in a Global Regulator in Bacteria–Ferric Uptake Regulator (Fur) Protein: Structure, Mössbauer Properties, and Functional Implication

Katigbak

Zhang

2012

J. Phys. Chem. Lett.

View full text Add to dashboard Cite

Fur protein plays key roles in regulating numerous genes in bacteria and is essential for intracellular iron concentration regulation. However, atomic level pictures of the iron binding site and its functional mechanism remain to be established. Here we present results of the first quantum chemical investigation of various first- and second-shell models and experimental Mössbauer data of E. Coli Fur, including 1) the first robust evidence that site 2 is the Fe binding site with a 3His/2Glu ligand set, being the first case in non-heme proteins, with computed Mössbauer data in excellent accord with experiment; 2) the first discovery of a conservative hydrogen bonding interaction in the iron binding site based on X-ray and homology structures; 3) the first atomic level hypothesis of active site reorganization upon iron concentration increase, triggering the conformational change needed for its function. These results shall facilitate structural and functional studies of Fur family proteins.

show abstract

Experimentally calibrated computational chemistry of tryptophan hydroxylase: Trans influence, hydrogen-bonding, and 18-electron rule govern O2-activation

Cited by 8 publications

References 59 publications

Axial and equatorial ligand effects on biomimetic cysteine dioxygenase model complexes

Axial and equatorial ligand effects on biomimetic cysteine dioxygenase model complexes

Mono- and binuclear non-heme iron chemistry from a theoretical perspective

Iron Binding Site in a Global Regulator in Bacteria–Ferric Uptake Regulator (Fur) Protein: Structure, Mössbauer Properties, and Functional Implication

Contact Info

Product

Resources

About