Linear, template reaction

For the synthetic chemist [14], the synthetic behavior of an assembler is akin to a molecule that functions as a template (Figure 2) [13], The pick-and-place paradigm evoked by an assembler [1] suggests a molecule that grabs and positions two molecules for a reaction that leads to a covalent bond. Moreover, such structure behavior is reminiscent of a linear template, a ditopic molecule that juxtaposes, by way of molecular recognition and self-assembly [5], two molecules linearly to achieve a particular linking of atoms. 

Kelly observed entropy and solvent effects in the first synthetic system that operates as a linear template (Figure 3a) [15]. Specifically, a bifunctional molecule based on a 1,3-disubstituted benzene was found to organize two molecules in apolar media, by way of a N-H N and N-H O forces, for a regiocon-trolled Sn2 reaction. The reaction occurred six times faster than the same reaction without the template. The enhanced rate, however, was significantly less than an analogous intramolecular process. This was attributed, in part, to entropic effects... 

Since the work of Kelly, there have been very few reports that focus upon applications of synthetic linear templates to chemical synthesis. Most recent studies have focused on systems that self-replicate [13]. A synthetic system based on a barbituric acid has been shown to organize two cinnamates in apolar media, by way of N-H N and N-H O forces, for a regiocontrolled [2 + 2] ultraviolet-(UV) induced cycloaddition reaction (Figure 3b) [16]. Similar to the system of Kelly, a mixture of products was attributed to free rotation about C-C bonds of the reactants. 

To enable linear templates to be used as general devices for building molecules, we have identified an ability of rigid bifunctional molecules to serve as linear templates in the organized environment of the solid state [6-12], The templates operate by assembling two complementary molecules by way of hydrogen bonds for a UV-induced [2 + 2] cycloaddition reaction [18]. By using the solid state as a medium for reaction, we have been able to circumvent the structure effects of... 

The minimalist molecules that may be organized by a linear template within a molecular assembly for reaction are molecules with a single hydrogen-bond acceptor site. Thus, a single template may organize two stilbazoles in a head-to-head arrangement for a regiocontrolled photodimerization that produces a head-to-head cyclobutane product. 

The ability of a linear template to orient two identical pyridyl units in a face-to-face stacked arrangement suggested that a linear template might be used to assemble two unsymmetrical reactants for a head-to-head photodimerization. Since different combinations of hydrogen-bond acceptor sites may be employed for the reaction (i.e. I runs-1 -( -pyndyl)-2-(n/-pyridyl)e(hylene (where n,m =2, 3, or 4 n f m)), a general means to establish regiocontrol of the cycloaddition could be achieved. 

Most recently, the methods of template-directed solid-state synthesis were employed to constmct the [3]- and the [5]-ladderane. The construction involved a resorcinol derivative (5-methoxyresorcinol) as a linear template to organize pyridine-substituted polyenes for the reaction within discrete molecular assemblies in solids. The assemblies are... 

Run 10 iL of the PCR product on a 1 % agarose gel for verification of the reaction (include linearized template DNA as a control). The PCR product should be smaller by the size of the deletion compared to the control. Extract once with phenol/chloroform twice with chloroform. Precipitate the DNA by adding sodium acetate, pH 5.2 to 0.3Mand 2 vol of ethanol. Incubate on dry ice for 15 min. Spin, wash with cold 80% ethanol, and respin. Dry the pellet under vacuum and suspend the precipitated DNA in 20 pL of TE. 

The [2+2] photodimerization of olefins is the best studied reaction in the context of SCSC reactions in both co-crystals and single-component solids. Co-crystals that exhibit SCSC [2+2] photoreactivity have been achieved using both the host-guest and linear template approach. The reactive solids have involved neutral and ionic [49] species, and have been constructed primarily using hydrogen bonds. 

The application of linear templates to form reactive co-crystals relies on the ability of template molecules to juxtapose reactant olefins within finite molecular assemblies for reaction (Scheme 2.3.7) [42], By virtue of the finite nature of the molecular assembly, the reaction is expected to occur largely without disturbing the overall crystal structure. In that way, co-crystals involving linear templates can be expected to provide an environment suitable to achieve SCSC reactivity. The linear template... 

The ability of a SCSC reaction to occur within a finite molecular assembly based on a linear template was first demonstrated by MacGillivray and co-workers who utilized 1,8-naphthalenedicarboxylic acid as a template to assemble trans-1-(3-pyridyl)-2-(4-pyridyl)ethylene, via O-H - -N hydrogen bonds, fora regioconotrlled [2+2] photodimerization [55]. The SCSC reaction was found to proceed, upon UV-irradiation with 420 nm light, quantitatively to give the head-to-head photoproduct rctt-l,2-bis(3-pyridyl)-3,4-bis(4-pyridyl)cyclobutane. A comparison of the single-... 

Several review articles have dealt with various aspects of cycloaddition reactions. A short review has presented examples to illustrate the use to which tethered alkenes can be put in the synthesis of cyclobutenes. The photochemical (2 + 2)-cycloaddition of enones to ethene has been studied from a theoretical standpoint. A review has highlighted the use of linear templates to control photochemical reactions such as (2 + 2)-photocycloadditions. The stereochemical control of photochemical reactions in clay-intercalated compounds has been discussed. A review has highlighted the interdisciplinary nature of photochemistry. ... 

Mock et al. [44] have shown that cucurbituril 48 catalyzes the 1,3-dipolar cycloaddition shown in Scheme 1-13. Here, cucurbituril acts as a linear template note that linear refers to the reaction topology and not to the shape of the template. 49 and 50 bind inside the cavity of 48 by hydrogen bonding between the ammonium groups and the rims of the cucurbituril. The reaction between 49 and 50 is made faster and more regiospecific clean formation of 51 occurs. 

Scheme 1-19 (a) Statistical reaction and (b) coupling in the presence of a linear template. 

Kinetic templates accelerate reaction of bound substrates, which makes it tempting to quantify template effects in terms of rate enhancement . In this section, we will show how this can be misleading because such rate enhancements are concentration dependent. We will elucidate the parameters which determine the rate enhancement achieved with a kinetic template, by analyzing the thermodynamic and kinetic behavior of simple theoretical models, and applying these models to published template systems. Our theoretical models are similar to the Michaelis-Menten analysis of enzyme catalyzed reactions [51], except that we assume there is no catalytic turnover. First, we consider linear templates, then cyclization templates. In general, the rate of reaction varies as the reaction proceeds whenever we refer to rates in the following discussion, we mean initial rates. 

The reaction is facilitated by a linear template T. We will assume that this template has two independent, identical, binding sites both bind substrates with the same microscopic binding constant K, to give a binary complex S-T and a ternary complex S T S. 

The rate enhancement, plotted as a function of [S]q in Figure 1-5 (g), reaches a maximum value of 1 + 2EM-KI21 when [S]o = H(4K) (these are exact algebraic results, independent of the values of k, k2, and K). Curve (g) shows that it is misleading to state a rate enhancement for a linear template at some arbitrary concentration [S]q. The maximum rate enhancement occurs when the rates of the templated and untemplated reactions are both low the intermolecular reaction is barely perceptible whereas the reaction in the ternary complex is proceeding several orders of magnitude faster the observed rate enhancement is therefore very high. 

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