A Convenient Synthesis of 3-Methylthiobenzaldehyde

Requiring the title compound as a starting material, we were surprised to find only one published synthesis,¹ involving five steps with an overall yield of 15%. This is in contrast to the 2-and 4-alkylthiobenzaldehydes, which may be synthesised in one step by reaction of sodium alkanethiolates with the readily available halobenzaldehydes². 3-Halobenzaldehydes, although readily available, do not react under these conditions².     

Peroxygenase activity of cytochrome <Emphasis Type="Italic">c</Emphasis> peroxidase and three apolar distal heme pocket mutants: hydroxylation of 1-methoxynaphthalene

Background

The cytochrome P450s are monooxygenases that insert oxygen functionalities into a wide variety of organic substrates with high selectivity. There is interest in developing efficient catalysts based on the “peroxide shunt” pathway in the cytochrome P450s, which uses H₂O₂ in place of O₂/NADPH as the oxygenation agent. We report on our initial studies using cytochrome c peroxidase (CcP) as a platform to develop specific “peroxygenation” catalysts.

Results

The peroxygenase activity of CcP was investigated using 1-methoxynaphthalene as substrate. 1-Methoxynaphthalene hydroxylation was monitored using Russig’s blue formation at standard reaction conditions of 0.50 mM 1-methoxynaphthalene, 1.00 mM H₂O₂, pH 7.0_, 25°C. Wild-type CcP catalyzes the hydroxylation of 1-methoxynaphthalene with a turnover number of 0.0044?±?0.0001 min^-1. Three apolar distal heme pocket mutants of CcP were designed to enhance binding of 1-methoxynaphthalene near the heme, constructed, and tested for hydroxylation activity. The highest activity was observed for CcP(triAla), a triple mutant with Arg48, Trp51, and His52 simultaneously mutated to alanine residues. The turnover number of CcP(triAla) is 0.150?±?0.008 min^-1, 34-fold greater than wild-type CcP and comparable to the naphthalene hydroxylation activity of rat liver microsomal cytochrome P450. While wild-type CcP is very stable to oxidative degradation by excess hydrogen peroxide, CcP(triAla) is inactivated within four cycles of the peroxygenase reaction.

Conclusions

Protein engineering of CcP can increase the rate of peroxygenation of apolar substrates but the initial constructs are more susceptible to oxidative degradation than wild-type enzyme. Further developments will require constructs with increased rates and selectivity while maintaining the stability of wild-type CcP toward oxidative degradation by hydrogen peroxide.

     

Photochemical charge separation in closely positioned donor-boron dipyrrin-fullerene triads

A series of molecular triads, composed of closely positioned boron dipyrrin-fullerene units, covalently linked to either an electron donor (donor(1)-acceptor(1)-acceptor(2)-type triads) or an energy donor (antenna-donor(1)-acceptor(1)-type triads) was synthesized and photoinduced energy/electron transfer leading to stabilization of the charge-separated state was demonstrated by using femtosecond and nanosecond transient spectroscopic techniques. The structures of the newly synthesized triads were visualized by DFT calculations, whereas the energies of the excited states were determined from spectral and electrochemical studies. In the case of the antenna-donor(1)-acceptor(1)-type triads, excitation of the antenna moiety results in efficient energy transfer to the boron dipyrrin entity. The singlet-excited boron dipyrrin thus generated, undergoes subsequent energy and electron transfer to fullerene to produce a boron dipyrrin radical cation and a fullerene radical anion as charge-separated species. Stabilization of the charge-separated state in these molecular triads was observed to some extent.