Modelling the site of bromide binding in vanadate-dependent bromoperoxidases?

Dalton Transactions Pub Date: 2012-03-14 DOI: 10.1039/C2DT12287A

Abstract

Treatment of Boc-protected (S)-serine (Ser) methyl ester with triphenylphosphine bromide Ph3PBr (intermittently generated from PPh3 and N-bromosuccinimide) yields Boc-3-bromoalanine (R)-Boc–BrAlaMe and, after deprotection, bromoalanine methyl ester (R)-BrAlaMe in the form of its hydrobromide. Boc–BrAlaMe and BrAlaMe have been structurally characterised. The reaction between BrAlaMe, salicylaldehyde (sal) and VO2+ results in the formation of Schiff base complexes of composition [VO(sal–BrAlaMe)solv]+ (solv = CH3OH: 3, THF: 5) and [VO(sal–BrAla)THF] 4. DFT calculations of the structures of 3, 4 and 5, based on the B3LYP functional and employing the triple zeta basis set 6-311++g(d,p), provide distances Br?V = 4.0 ± 0.1 ?, if some distortion of the dihedral angle ∠N–C–C–Br is allowed (affording a maximum energy of ca. 45 kJ mol?1), and thus model Br?V distances detected by X-ray methods in bromoperoxidases from the marine algae Ascophyllum nodosum and Corallina pilulifera. The DFT calculations have been validated by comparing calculated and found structures, including the new complex [VVO(Amp–sal)OMe(MeOH)] (1, Amp is the aminophenol moiety) and the known complex [VO(L-Ser–van)H2O] (van = vanillin). Additional validation has been undertaken by checking experimental against calculated (BHandHLYP) EPR spectroscopic hyperfine coupling constants. Complexes containing bromine as a substituent at the phenyl moiety of a Schiff base ligand do not allow for an appropriate simulation of the Br?V distance in peroxidases. The closest agreement, d(Br?V) = 4.87 ?, is achieved with [VO(3Br–salSer)THF] (6), where 3Brsal–Ser is the dianionic Schiff base formed between 3-Br-5-NO2-salicylaldehyde and serine.

Graphical abstract: Modelling the site of bromide binding in vanadate-dependent bromoperoxidases
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