Linear templates

Consider the situation where two molecules of a substrate S, of initial concentration [S]o, react together to yield a product P  

The bimolecular rate constant for the untemplated reaction is 2. so the initial rate of the reaction in the absence of a template is  

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 concentrations of unbound substrate [S] and unbound template [T] are related to the concentration of these complexes by the equilibrium constant. 

The unimolecular rate constant for conversion of the ternary complex S-T-S to the template product T - P is /cj. 

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Scheme 47 Linear templates direct the phodimerisation of olefin 96... 

MacGillivray s group has employed rigid bifunctional molecules [42], such as 1,3-dihydroxybenzene and 1,8-naphthalenedicarboxyHc acid [42a], as linear templates to organize reactants such as fra s-l,2-bis(4-pyridyl)ethylene via hydrogen bonds for single and multiple photoinduced [2+2] cycloadditions, for the template-controlled synthesis of a l,2,3,4-(4-pyridyl)cyclobutane] [42b] and also of paracyclophanes [42d]. Very recently, [ ]ladderanes ( =2,3) have been synthesized in the solid state by UV irradiation of 2(5-methoxyresorci-nol) 2(4-pyr-poly-m-ene) (m=2,3) [42e]. 

Very recently, MacGillivray et al. succeeded in the supramolecular construction of molecular ladders in the solid state using a linear template approach [48]. They designed the cocrystals 1,3-benzenediol (resorcinol) or a derivative with an all-trans-bis(4-pyridyl)butadiene or hexatriene, in which two resorcinol molecules preorganize two polyene molecules through two hydrogen bond interactions, for [2-1-2] photoaddition (Scheme 5). In this design, two polyenes would... 

The formation of complexes involved two steps. In the first step, the ionene bromide was converted to ionene hydroxide by replacing the Br ions with OH ions. In the second step, the equivalent quantities of acid and ionene were mixed together. Polymerizations were carried out mostly in water-isopropanol solution. AIBN or 4,4-azobis-4-cyanovaleric acid was used as initiator. Polymerization of p-styrene sulfonic acid onto various ionenes was studied as a function of the charge density of the template. It was shown that a linear dependence of rate on charge density prevailed. From the results obtained, the authors concluded that the monomeric counterions possess mobility along the linear template. PolyCvinyl sulfonate) prepared on the template displays a different stereo-structure from polyCvinyl sulfonate) prepared in solution. 

Scheme 6 Combined Solid-Phase and Solution Strategy After Chain Assembly, the Linear Template Sequence Is Cleaved from the Resin, Cyclized in Solution and Re-immobilized on a Resin (Steps a-d) Orthogonal Protection Allows for the Construction of Protein Surface Mimetics, TASP Molecules, or Receptor Mimetics 52 53 ...

Split-Primer Design for the Construction of PCR-Generated Linear Template DNAs for Transcription and Translation... 

Supramolecular Control of Reactivity in the Solid State Using Linear Templates... 

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. 

Although chemists have designed molecules that function as linear templates, the concept of the assembler goes beyond the synthetic abilities of linear templates... 

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... 

Figure 3 Artificial linear templates that operate in the liquid phase (a) linear template of Kelly and (b) linear template of Bassani.

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... 

To develop a system of linear templates to control the [2 + 2] cycloaddition in the solid state, we turned to crystal structure studies involving a bis(resorcinol) anthracene [19,20]. In particular, it had been shown that co-crystallization of a l,8-bis(resorcinol)anthracene with anthraquinone yielded a one-dimensional (1-D) hydrogen-bonded polymer wherein each resorcinol unit of the anthracene organized, by way of O-H O hydrogen bonds, two quinones in a face-to-face... 

To expand the scope of products accessible using linear templates, and thereby enable linear templates to begin to fulfill the design principles of assemblers,... 

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. 

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