Dual-activation

The combination of electrochemistry and photochemistry is a fonn of dual-activation process. Evidence for a photochemical effect in addition to an electrochemical one is nonnally seen m the fonn of photocurrent, which is extra current that flows in the presence of light [, 89 and 90]. In photoelectrochemistry, light is absorbed into the electrode (typically a semiconductor) and this can induce changes in the electrode s conduction properties, thus altering its electrochemical activity. Alternatively, the light is absorbed in solution by electroactive molecules or their reduced/oxidized products inducing photochemical reactions or modifications of the electrode reaction. In the latter case electrochemical cells (RDE or chaimel-flow cells) are constmcted to allow irradiation of the electrode area with UV/VIS light to excite species involved in electrochemical processes and thus promote fiirther reactions. 

Another kind of dual activity was given to type I MAI by incorporating hydroxy-phenyl-propanedione-dioxime (HPO) group alternatively with ordinary azo group [Eq. (5)] [11]. 

Without question, the most significant advance in the use of sulfur-centered nucleophiles was made by Shibasaki, who discovered that 10 mol% of a novel gallium-lithium-bis(binaphthoxide) complex 5 could catalyze the addition of tert-butylthiol to various cyclic and acyclic meso-epoxides with excellent enantioselectiv-ities and in good yields (Scheme 7.11) [21], This work builds on Shibasaki s broader studies of heterobimetallic complexes, in which dual activation of both the electrophile and the nucleophile is invoked [22]. This method has been applied to an efficient asymmetric synthesis of the prostaglandin core through an oxidation/ elimination sequence (Scheme 7.12). 

Dual activation of nucleophile and epoxide has emerged as an important mechanistic principle in asymmetric catalysis [110], and it appears to be particularly important in epoxide ARO reactions. Future work in this area is likely to build on the concept of dual substrate activation in interesting and exciting new ways. 

Proguanil appears to have a dual activity. Part of it is metabolized to cycloguanil, which subsequently inhibits the protozaon dihydrofolate reduc-tase/thymidylate synthase (DHFR/TS) (Fig. 4). In addition, the native form, proguanil itself, exerts a potent antimalarial activity, especially in combination with other antimalarial drugs. The target of proguanil is unknown. 

Mermerian AH, Fu GC (2003) Catalytic enantioselective synthesis of quaternary stereocenters via intermolecular C-acylation of silyl ketene acetals dual activation of the electrophile and the nucleophile. J Am Chem Soc 125 4050-4051... 

Proteins B, D and P also amplify the effects ofthe classical pathway in that some of the 3b generated by this pathway interacts with these proteins to form additional C3 convertase that supplements that provided by C4b.2a. Likewise, enhanced cleavage of C5 occurs due to the dual activity of C4.2a.3b and C3b.Bb.C3b complexes. 

Compton RG, Eklund JC, Marken F (1997) Dual activation coupling ultrasound to electrochemistry - an overview. Electrochim Acta 42 2919-2927... 

In 1995, Perkin-Ehner introduced a new enzyme rTth-DNA polymerase with a dual activity. It can perform both RT and PCR in the presence of manganese acetate buffer, sense and antisense primers, and nucleotides. This protocol is easier to perform and reduces total in situ RT-PCR reaction time (46). 

Another target defined for anionized albumins are cells of the immune system that have been infected with the human immunodeficiency virus (HIV). Suc-HSA and Aco-HSA are potent inhibitors of HIV-1 repheation in vitro [48]. Thus, auionized albumins can be regarded as pharmacologicaUy active proteins, that can be used either as such, or as dual-active cou-... 

This dual activity against both nematode and arthropod parasites of animals was an unexpected bonus from a screen for anthelmintic agents. The reason for this broad activity lies in their mode of action. They act by interfering with y-aminobutyric acid (GABA) mediated neurotransmission. When treated with avermectin, the nematode Ascaris suum becomes paralyzed although it retains normal muscle tone (17). Picrotoxin, an antagonist of GABA, can reverse the effect of avermectin on neurotransmission vitro. 

Newer types of the dinuclear vanadium(IV) complex catalysts 84 have been developed. The abovementioned dinuclear vanadium complexes possess a VO V linkage whereas the ESR study on the catalyst 84 revealed no V—O—V linkage. The sense of enantioselection by the catalyst 84 of the (R,5,5)-structure is opposite to that of the binuclear complex 78a of the same (R,5,5)-structure. These results suggested two active sites attached to the binaphthyl skeleton in the catalyst 84 performed the dual activation of 2-naphthols in the oxidative couphng to achieve high enantioselectivity ... 

We reported a catalytic enantioselective cyanosUylation of ketones that produces chiral tetrasubstituted carbons from a wide range of substrate ketones [Eq. (13.31)]. The catalyst is a titanium complex of a D-glucose-derived ligand 47. It was proposed that the reaction proceeds through a dual activation of substrate ketone by the titanium and TMSCN by the phosphine oxide (51), thus producing (l )-ketone cyanohydrins ... 

Corey reported a catalytic enantioselective cyanosilylation of methyl ketones using combination of a chiral oxazaborolidinium and an achiral phosphine oxide, [Eq. (13.23)]. An intermolecular dual activation of a substrate by boron and TMSCN by the achiral phosphine oxide (MePh2PO) is proposed as a transition-state model (54). The same catalyst was also used for cyanosilylation of aldehydes ... 

In 1996, Carreira reported a catalytic enantioselective aUylation of aldehydes using BlNOL-modified Tip4. More recently, Kobayashi reported a catalytic enantioselective aUylation of hydrazono esters in aqueous media using ZnF2-chiral diamine complex, [Eq. (13.36)]. In both reactions, reaction mechanism via dual activation of the substrate by Lewis acid metals and aUylsUanes by fluoride is proposed ... 

These inhibitors act directly on the enzyme without the necessity for incorporation into the DNA. In theory, this should shift the dual activity of reactivation of silenced genes and cytotoxicity towards the epigenetic effects which may result in reduced side-effects. But the proof for that remains yet to be established. 

A method using dual activation has been developed in which a Lewis acid activates the aldehyde with concomitant nucleophilic activation of the allylic silicon reagent with fluoride anion. Thus, by using a BINOL-based titanium... 

Oximes of certain sterols were examined as inhibitors of cholesterol biosynthesis, by suppressing two enzymes that are involved in the biochemical pathway of cholesterol biosynthesis. This dual activity indicates a promising series of biologically reactive oximes (and oxime ethers) capable of reducing cholesterol levels . 

As discussed previously, the activation loop can also flip into an active state, and the pyridopyrimidine derivatives and dasatinib are able to bind ABLl whether the activation loop is in the closed or open position (inactivated or activated) (92). Thus, binding is not affected by the activation state. Dasatinib and related compounds are also smaller in size than IM, so the P-loop must undergo major conformational changes on binding with IM, whereas only minimal changes occur with dasatinib and related compounds. This dual activity of dasatinib also raises the question as to whether its broader activity may have broader effects, including potentially adverse effects in the treatment of patients. 

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