Alkaline phosphatase inhibition by vanadyl-β-diketone complexes: electron density effects

Figures & data

Figure 1.  Substituted VO(β-diketone)₂ complexes: VO(acac)₂, bis(acetylacetonato)oxovanadium(IV); VO(Meacac)₂, bis(3-methylacetylacetonato)oxovanadium(IV); VO(Clacac)₂, bis(3-chloroacetylacetonato)oxovanadium(IV); VO(CF₃ac)₂, bis(1,1,1-trifluoroacetylacetonato)oxovanadium(IV); and VO(Benzac)₂, bis(benzoylacetonato)oxovanadium(IV).

Figure 2.  Temperature dependence of k_cat for calf-intestine APase catalyzed pNPP dephosphorylation.

Figure 3.  Panel A. Plot of APase activity versus pNPP concentration at different VO(Clacac)₂ inhibitor concentrations. Panel B. Plots of k′_cat versus inhibitor concentration and K′_m versus inhibitor concentration.

Table I.  K_i values for inhibitors against calf-intestine APase at pH 8 and 37°C.

Compound	Ki (μM)
VO(CF3ac)2	0.07 ± 0.01
VO(Clacac)2	0.15 ± 0.01
VO(Meacac)2*	0.34 ± 0.04
VO(Benzac)2	0.40 ± 0.05
VO(acac)2	0.43 ± 0.04
Na3VO4	0.49 ± 0.04
VOSO4	0.55 ± 0.06
VO(acac)2·4-Mepy	0.69 ± 0.04
VO(Clacac)2·4-Mepy	1.04 ± 0.13

* Oxidizes to vanadium(V), possibly [VO(Meacac)₂]⁺.

Table II.  Variations in physical properties of VO(β-diketone)₂ complexes.

	VO charge (au)^a			IR: ν(V = O)(cm^− 1)^b
Compound	gas	soln.	V = O bond length (Å)	calc.	obs.	χG (Pauling)^c
VO(Meacac)2	0.733	0.672	1.572	1072	997	2.30 (CH3)
VO(acac)2	0.745	0.691	1.570	1076	997	2.20 (H)
VO(Benzac)2^d	0.750	0.691	1.571	1074	997	2.58 (C6H5)′
VO(Clacac)2	0.770	0.733	1.568	1080	1048	3.16 (Cl)
VO(CF3ac)2^d	0.783	0.752	1.565	1086	1056	3.32 (CF3)′

^a Mulliken charge in atomic units (au) on the vanadyl group in the gas-phase and aqueous solution

^b V = O bond stretching frequency. The calculated frequencies were obtained using a scaling factor of 0.963. The experimental frequencies were obtained from the infrared spectra of polycrystalline samples run as nujol mulls with air as the background

^c Pauling group electronegativity for substituents (R or R′) of Figure 1. [34]

^d Trans configuration.

Figure 4.  Correlation of K_i (μM) for VO(β-diketone)₂ complexes in aqueous solution with the calculated Mulliken charge on the VO group in atomic units, R = 0.995. VO(Meacac)₂ oxidizes immediately to vanadium(V) under assay conditions.

G Cathala, C Brunel, D Chappelet-Tordo, and M Lazdunski. (1975). Bovine kidney alkaline phosphatase catalytic properties, subunit interactions in the catalytic process, and mechanism of Mg2+ stimulation. J Biol Chem 250:6046–6053.

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