58088-50-9Relevant articles and documents
Interplay Between Steric and Electronic Effects: A Joint Spectroscopy and Computational Study of Nonheme Iron(IV)-Oxo Complexes
Mukherjee, Gourab,Alili, Aligulu,Barman, Prasenjit,Kumar, Devesh,Sastri, Chivukula V.,de Visser, Sam P.
, p. 5086 - 5098 (2019/03/17)
Iron is an essential element in nonheme enzymes that plays a crucial role in many vital oxidative transformations and metabolic reactions in the human body. Many of those reactions are regio- and stereospecific and it is believed that the selectivity is guided by second-coordination sphere effects in the protein. Here, results are shown of a few engineered biomimetic ligand frameworks based on the N4Py (N,N-bis(2-pyridylmethyl)-N-bis(2-pyridyl)methylamine) scaffold and the second-coordination sphere effects are studied. For the first time, selective substitutions in the ligand framework have been shown to tune the catalytic properties of the iron(IV)-oxo complexes by regulating the steric and electronic factors. In particular, a better positioning of the oxidant and substrate in the rate-determining transition state lowers the reaction barriers. Therefore, an optimum balance between steric and electronic factors mediates the ideal positioning of oxidant and substrate in the rate-determining transition state that affects the reactivity of high-valent reaction intermediates.
Folic acid conjugates of a bleomycin mimic for selective targeting of folate receptor positive cancer cells
Geersing, Arjan,de Vries, Reinder H.,Jansen, Gerrit,Rots, Marianne G.,Roelfes, Gerard
supporting information, p. 1922 - 1927 (2019/06/05)
A major challenge in the application of cytotoxic anti-cancer drugs is their general lack of selectivity, which often leads to systematic toxicity due to their inability to discriminate between malignant and healthy cells. A particularly promising target for selective targeting are the folate receptors (FR) that are often over-expressed on cancer cells. Here, we report on a conjugate of the pentadentate nitrogen ligand N4Py to folic acid, via a cleavable disulphide linker, which shows selective cytotoxicity against folate receptor expressing cancer cells.
Selective C-H halogenation over hydroxylation by non-heme iron(iv)-oxo
Rana, Sujoy,Biswas, Jyoti Prasad,Sen, Asmita,Clémancey, Martin,Blondin, Geneviève,Latour, Jean-Marc,Rajaraman, Gopalan,Maiti, Debabrata
, p. 7843 - 7858 (2018/10/31)
Non-heme iron based halogenase enzymes promote selective halogenation of the sp3-C-H bond through iron(iv)-oxo-halide active species. During halogenation, competitive hydroxylation can be prevented completely in enzymatic systems. However, synthetic iron(iv)-oxo-halide intermediates often result in a mixture of halogenation and hydroxylation products. In this report, we have developed a new synthetic strategy by employing non-heme iron based complexes for selective sp3-C-H halogenation by overriding hydroxylation. A room temperature stable, iron(iv)-oxo complex, [Fe(2PyN2Q)(O)]2+ was directed for hydrogen atom abstraction (HAA) from aliphatic substrates and the iron(ii)-halide [FeII(2PyN2Q)(X)]+ (X, halogen) was exploited in conjunction to deliver the halogen atom to the ensuing carbon centered radical. Despite iron(iv)-oxo being an effective promoter of hydroxylation of aliphatic substrates, the perfect interplay of HAA and halogen atom transfer in this work leads to the halogenation product selectively by diverting the hydroxylation pathway. Experimental studies outline the mechanistic details of the iron(iv)-oxo mediated halogenation reactions. A kinetic isotope study between PhCH3 and C6D5CD3 showed a value of 13.5 that supports the initial HAA step as the RDS during halogenation. Successful implementation of this new strategy led to the establishment of a functional mimic of non-heme halogenase enzymes with an excellent selectivity for halogenation over hydroxylation. Detailed theoretical studies based on density functional methods reveal how the small difference in the ligand design leads to a large difference in the electronic structure of the [Fe(2PyN2Q)(O)]2+ species. Both experimental and computational studies suggest that the halide rebound process of the cage escaped radical with iron(iii)-halide is energetically favorable compared to iron(iii)-hydroxide and it brings in selective formation of halogenation products over hydroxylation.
