Multiple pathways

Figure Al.6.31. Multiple pathway interference interpretation of pump-dump control. Since each of the pair of pulses contains many frequency components, there are an infinite number of combination frequencies which lead to the same fmal energy state, which generally interfere. The time delay between the pump and...

Figure 6.5 (a) Some proteins such as barnase fold through one major pathway whereas others fold through multiple pathways. 

Weissman, J.S. All the roads lead to Rome The multiple pathways of protein folding. Chem. Biol. 2 255-260, 1995. 

Multiple pathways are a major concern since depostion of PIC would have occurred. Specific soil conditions determine attenuation rates of penta PIC leachate. Once penta reaches the water table, other transport and fate processes become important. Penta exists in two forms ionized and non-ionized. The ionized form is soluble in water, while the non-ionized form is not. The ratio of the two forms in water is dependent on the pH of the aquifer. In alkaline environments penta PIC tend to be more soluble and more susceptible to advective transport and biological decay. Half-lives of penta leachate in groundwater have been estimated ranging from 27 days to 58 years. 

Creosote is a complex mixture of toxic chemicals, which can have both immediate and chronic effects on exposed organisms. PIC of creosote are of particular concern due to long half-lives of some chemicals, and because of multiple pathways to the environment from ash and soot. 

Environmental Protection Agency. (1993). Multiple Pathways to Supe.r-EBiae.nt ReBigerators. EPA-430-R-93-008. Washington, DC Author. 

Bile acid synthesis from cholesterol is the prime pathway for cholesterol catabolism. Cholesterol is converted into bile acids via multiple pathways which involve 17 different enzymes. Many of these enzymes are predominantly expressed in the liver and are localized in several different subcellular... 

Since the SUMO pathway affects multiple pathways ranging from transcription, DNA repair, and intracellular trafficking over cell signaling and cell cycle control to basic metabolism, it is not suiprising that links to diseases and viral assaults are emerging. However, the field is not yet at a stage sufficiently developed for pharmacological intervention. Below we will describe selected examples for links of the SUMO pathway to diseases and viral functions. 

Even though the rate of radical-radical reaction is determined by diffusion, this docs not mean there is no selectivity in the termination step. As with small radicals (Section 2.5), self-reaction may occur by combination or disproportionation. In some cases, there are multiple pathways for combination and disproportionation. Combination involves the coupling of two radicals (Scheme 5.1). The resulting polymer chain has a molecular weight equal to the sum of the molecular weights of the reactant species. If all chains are formed from initiator-derived radicals, then the combination product will have two initiator-derived ends. Disproportionation involves the transfer of a P-hydrogen from one propagating radical to the other. This results in the formation of two polymer molecules. Both chains have one initiator-derived end. One chain has an unsaturated end, the other has a saturated end (Scheme 5.1). 

Benke GM, Murphy SD. 1974. The influence of age and sex on the toxicity and multiple pathways of metabolism of methyl parathion and parathion in rats. Toxicol Appl Pharmacol 29 125. 

The following sections discuss classes of reactions in which multiple pathways appear, outline methods of probing and predicting their behavior, provide representative examples of such reactions, and examine the ramifications of multiple pathways on our understanding of reaction mechanisms. 

Pathways through abstraction and addition-elimination mechanisms may lead to the same product channel. However, they will only compete significantly when the energy and entropy barriers (or free energy barriers AG = AH — TAS) for the two mechanisms are comparable. In these cases, they make excellent candidates for multiple pathway studies because several experimental approaches discussed in Section III are suited to detect the competition. 

Multiple pathways leading to the same product channel can also be observed in a reaction when there are a sufficient number of identical atoms, thereby allowing different intermediate structures to yield the same products. In these cases, the mechanisms in the two pathways are often quite similar, but involve differing positions of identical atoms on the reactants. The different pathways often involve formation of ring intermediates in which the rings have different sizes. A simple example of this class is the photodissociation of vinyl chloride [9]... 

The possibility of multiple pathways arising from identical atoms becomes greater as the total number of atoms increases because the possibility to form... 

However, deep potential wells, including those on the MEP, may be avoided in the reaction mechanism. Forces exerted on the downhill slope of saddle points or ridges on the PES can impart sufficient velocity (both magnitude and direction) to steer the trajectory past a well, just as a skilled kayaker can avoid a whirlpool in the middle of a river by choosing an appropriate velocity well before the whirlpool is encountered. Multiple pathways can arise when the initial conditions upon surmounting the barrier either facilitate or hinder the avoidance of the well. The reaction OH + CH3F discussed in Section V is an example of this phenomenon. 

Reactions without wells can also exhibit multiple pathways due to deviation from the MEP. While many trajectories may follow the MEP over a saddle point, alternative pathways arise when forces on the PES steer away from the saddle point, typically into relatively flat regions of the PES, before finding an additional path to the same exit channel. The roaming mechanisms recently elucidated in the photodissociation of formaldehyde and acetaldehyde, and the reaction of CH3 + O, are examples of this phenomenon, and are discussed in Section V. 

Multiple pathways to the same product channel therefore occur via nonadiabatic transitions that lead from the initial electronic state to at least one other electronic state before converging on the product asymptote. Two examples are presented in this chapter the photodissociations CH2O —> H + HCO and H2O H + OH. There is evidence of similar effects in the photodissociation HNCO H + NCO [13]. 

It is challenging experimentally to study two pathways leading to a single product channel for the simple reason that the products in either case are structurally identical. Nevertheless, there are several methods, each applicable to certain classes of reactions, that can distinguish the presence of multiple pathways. 

A qualitatively different approach to probing multiple pathways is to interrogate the reaction intermediates directly, while they are following different pathways on the PES, using femtosecond time-resolved pump-probe spectroscopy [19]. In this case, the pump laser initiates the reaction, while the probe laser measures absorption, excites fluorescence, induces ionization, or creates some other observable that selectively probes each reaction pathway. For example, the ion states produced upon photoionization of a neutral species depend on the Franck-Condon overlap between the nuclear configuration of the neutral and the various ion states available. Photoelectron spectroscopy is a sensitive probe of the structural differences between neutrals and cations. If the structure and energetics of the ion states are well determined and sufficiently diverse in... 

In principle, these approaches are very attractive because they probe multiple pathways in the critical regions where the pathways are separated, but in practice these are extremely challenging experiments to conduct, and the interpretation of results is often quite difficult. Furthermore, these experiments are difficult to apply to bimolecular collisions because of the difficulty of initiating the reaction with sufficient time resolution and control over initial conditions. 

Like the previous reaction, multiple pathways in the HO2 - - O3 reaction arise because of the participation of identical atoms. However, in this case the two... 

The final example of a reaction in which multiple pathways arise from the participation of identical atoms is the reaction HCCO + O2. This reaction demonstrates another general feature of pathway competition when unsaturated species are involved, namely, the possibilities for formation of ring intermediates of different sizes. 

Section V.D described the competition of two pathways in the H2 + CO molecular channel. There are also multiple pathways to the radical channel producing H + HCO. In aU cases, highly vibrationally excited CH2O is prepared by laser excitation via the So transition. In the case of the radical channel discussed in this section, multiple pathways arise because of a competition between internal conversion (S o) and intersystem crossing ( i T ), followed by evolution on these electronic states to the ground-state H + HCO product channel. Both electronic states So and Ti correlate adiabatically with H + HCO products, as shown in Fig. 7. 

The study of multiple pathways leading to a single product channel provides a stringent test of our understanding of the potential energy surface and the calculations that use it to predict reaction outcomes. Although there are not many examples to date of pathway competitions, the increasing prominence of such systems, coupled with advances in experiment and theory that facilitate their study, promises a rich future in this normally hidden facet of reaction mechanisms. 

Johnson GR, RH Olsen (1997) Multiple pathways for toluene degradation in Burkholderia sp. strain JS150. Appl Environ Microbiol 63 4047-4052. 

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