Dichloroacetate, DCA

Since Bahnemann and co-workers have observed that a comparatively high amount of trapped holes are formed when partially platinized titanium dioxide particles are subjected to ultra band gap irradiation (cf. Fig. 7.6), they have chosen this system to study the dynamics of the photocatalytic oxidation of the model compounds dichloroacetate, DCA", and SCN- [7]. To explain their experimental observations these authors have used a model assuming two energetically different types of hole traps (see our detailed discussion above). 

Figure 7-2. Reactions of the pyruvate dehydrogenase (PDU) multienzyme complex (PDC). Pyruvate is decarboxylated by the PDH subunit (I ,) in the presence of thiamine pyrophosphate (TPP). The resulting hydroxyethyl-TPP complex reacts with oxidized lipoamide (LipS3), the prosthetic group of dehydrolipoamide transacetylase (Ii2), to form acetyl lipoamide. In turn, this intermediate reacts with coenzyme A (CoASH) to yield acetyl-CoA and reduced lipoamide [Lip(SH)2]. The cycle of reaction is completed when reduced lipoamide is reoxidized by the flavoprotein, dehydrolipoamide dehydrogenase (E3). Finally, the reduced flavoprotein is oxidized by NAD+ and transfers reducing equivalents to the respiratory chain via reduced NADH. PDC is regulated in part by reversible phosphorylation, in which the phosphorylated enzyme is inactive. Increases in the in-tramitochondrial ratios of NADH/NAD+ and acetyl-CoA/CoASH also stimulate kinase-mediated phosphorylation of PDC. The drug dichloroacetate (DCA) inhibits the kinase responsible for phosphorylating PDC, thus locking the enzyme in its unphosphory-lated, catalytically active state. Reprinted with permission from Stacpoole et al. (2003).

Direct hole transfer was also observed when dichloroacetate (DCA) was used as the electron donor [26]. While it was obvious that deeply trapped holes /zt+rd do not react with dichloroacetate, it was observed that the /zt+rd concentration is reduced considerably in the presence of DCA", either the free holes, h+, can be directly transferred to adsorbed DCA" molecules (reaction 19) or shallowly trapped holes, ht+r s, are detrapped (reaction 11) to react with DCA" in the nanosecond time scale via reaction 22. 

Sodium dichloroacetate (DCA) is a small molecule that has multiple effects on intermediary metabolism. Of primary interest in the current example is the ability of DCA to activate pyruvate dehydrogenase, the rate-limiting enzyme for the conversion of pyruvate to acetyl CoA. The pyruvate concentration is, in turn, replenished by oxidation of lactate, thereby replenishing concentrations of the latter. Such a reduction may decrease the morbidity in head trauma, where local (CSF) elevated lactate is thought to be neurotoxic. 

Figure 14 Separation of haloacetic acids and inorganic anions. Column Cryptand A15(x (150mm x 3mm) eluent gradient —8 to 3min, lOmM NaOH t = 3min, lOmM LiOH. Monochloro-cacetic (MCA), monobromoacetic (MBA), dichloroacetic (DCA), bromochloroacetic (BCA), dibromoacetic (DBA), trichloroacetic (TCA), monobromodichloroacetic (MBDCA), monochlorodibro-moacetic (MCDBA), and tribromoacetic (TBA) acids. (Reproduced from Ref. 64. Elsevier, 2008.)...

The kinetics of hole transfer is somewhat different. It could be studied very well with Pt/Ti02 because here the electrons are rapidly transferred to the Pt islands so that a pure hole spectrum (Figure 9.12) remains after about 1 ps. The corresponding decay curves in the presence of dichloroacetate (DCA) as a hole acceptor are... 

An ideal therapy should increase GBM [glioblastoma] apoptosis, overcome the molecular heterogeneity, inhibit angiogenesis, and cross the blood-brain barrier while having minimal systemic toxicity. On the basis of our recent findings in animal models [phase I], we hypothesized that the orphan small-molecule dichloroacetate (DCA) fulfills these criteria and may be effective in the treatment of GBM in humans."... 

DCA = dichloroacetic acid TFA = trifluoroacetic acid TFE = trifluoroethanol EDC = ethylene dichloride DMF = dimethylformamide... 

In ion-exclusion chromatography, ions are separated from nonelectrolytes by an ion-exchange column. Nonelectrolytes penetrate the stationary phase, whereas half of the ions are repelled by the fixed charges. Because electrolytes have access to less of the column volume, they are eluted before nonelectrolytes. The chromatogram here shows the separation of trichloroacetic acid (TCA, pKa = 0.5), dichloroacetic acid (DCA, pK.a = 1.1), and... 

All three chloroacetic acids (chloroacetic acid [MCA], dichloroacetic acid [DCA], and trichloroacetic acid [TCA]) are naturally occurring (7), with TCA being identified in the environment most frequently (reviews (278, 405 108)). However, these chlorinated acetic acids also have anthropogenic sources. The major source of natural TCA appears to be the enzymatic (chloroperoxidase) or abiotic degradation of humic and fulvic acids, which ultimately leads to chloroform and TCA. Early studies (409) and subsequent work confirm both a biogenic and an abiotic pathway. Model experiments with soil humic and fulvic acids, chloroperoxidase, chloride, and hydrogen peroxide show the formation of TCA, chloroform, and other chlorinated compounds (317, 410-412). Other studies reveal an abiotic source of TCA (412, 413). 

Hirvonen et al. (1995) evaluated the feasibility of the UV/H202 process for the removal of trichloroethylene (TCE) and erythromycin (perchloroethylene [PCE]) in contaminated groundwater. The formation of chloroacetic acids (CAs) was used as an indication of partial degradation. The dominant byproduct, dichloroacetic acid (DCA), accounted for the major part of the total yield of CAs. The observed concentrations of trichloroacetic acid (TCA) and DCA were relatively low compared with the total amount of TCE and PCE degraded. The effect of initial concentrations of the parent compounds, hydrogen peroxide, and bicarbonate on the yield of by-product was inves-... 

While the initial height of the transient absorption signal attributed to energetically deep traps, iT d. i.e., the concentration of h+tr,d) is considerably decreased by an increasing dichloroacetate concentration, the kinetics of its decay is not effected. It was therefore concluded that h+ttid do not react with dichloroacetate [7 a]. However, since the h+trid concentration is reduced considerably in the presence of DCA" (cf. Fig. 7.5), either the free holes, h can be directly transferred to... 

The direct charge transfer to dichloroacetate proposed in reaction (7.21) requires that the scavenging molecules are adsorbed on the Ti02 surface prior to the adsorption of the photon. Otherwise, this reaction could not compete with the normal hole-trapping reactions (7.9) and (7.10). So the adsorption of the model compound DCA on the titanium dioxide surface prior to the bandgap excitation appears to be a prerequisite for an efficient hole scavenging. 

A kinetic and product study of the dichloroacetic acid (DCA) catalyzed chlorination of 1-methylpyrrole with a series of 3- and 4-substituted A -chlorobenzamides 325 under nitrogen, at 40 °C was carried out (Scheme 73) <2003T2125>. Chlorination at C-2 of the pyrrole ring leads to the formation of 2-chloro-l-methylpyrrole 326 and subsequently 2,5-dichloro-l-methylpyrrole 327. The total yield of attack at C-2 is therefore the sum of the yields of pyrroles 326 and 327. The yields of 2-chlorination (ca. 84%) and 3-chlorination (ca. 2.6%) were essentially constant as... 

Poly-y-benzyl-7-glutamate, M = 300,000 (1 g of solid or 25 mL of 2.5 weight percent solution) ethylene dichloride-dichloroacetic acid solvent (76 volume percent DCA) stored in polyethylene bottle wash acetone. The polypeptide can be obtained from Sigma Chemical Co., P.O. Eox 14508, St. Louis, MO 63178. Check the current Chem. Sources for other suppliers. 

The photocatalytic degradation of TCE was studied intensively, both in the liquid phase and in the gas phase. Unlike in the aqueous phase, where the quantum efficiency is no more than a few percents (Alberici and Jardim, 1997 Pruden and Ollis, 1983), the quantum efficiency in the gas phase can be higher than 100% (Upadhya and Ollis, 1998). This difference was attributed to the existence of two mechanisms. That the mechanism in the liquid phase was different than that in the gas phase could be deduced also by the fact that the intermediate products dichloroacetaldehyde (DCA) and dichloroacetic acid (DCAA) were identified only during liquid-phase photocatalysis (Pruden and Ollis, 1983). 

SYNS BICHLORACETIC ACID DCA DICHLORETHANOIC ACID 2,2-DICHLOROACETIC ACID DICHLOROETHANOIC ACID D KYSELINA DICHLOROCTOVA URNER S LIQUID... 

Fig. 3. Intrinsic viscosity-molecular weight relationship of poly-7-benzyl-L-glutamates. The open circles represent the randomly coiled form and other symbols the a-helical form. The line of steeper slope is a plot of Simha s equation. Abbreviations dichloroacetic acid, DCA chloroform saturated with formamide, C-F dimethyl formamide, DMF light scattering, L.S. weight-average molecular weight, A/m. Reproduced from Doty et al. (1956).

Reduced mean residue rotations for helical L-polypeptides extrapolated to meso-composition. Solvent abbreviations CHCI3, chloroform DCA, dichloroacetic acid DMF, dimethyl formamide. 

All ao and 6o measurements are based on Xo = 212 mu. Solvent abbreviations CHCli, chloroform DCA, dichloroacetic acid. 

A second collagen sample was bovine Achilles tendon collagen (Schwartz Mann, Inc.). This material resisted solvation in all simple aqueous solutions and even in strong acids, but it could be solubilized with time by dichloroacetic acid (DCA). Thus, films formed from this sample had to be cast from DCA. 

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