Douglas Philp

Applying biological principles to the assembly and selection of synthetic superstructures

It has become clear over the past two decades that, in order to create functional synthetic nanoscale structures, the chemist must exploit a fundamental understanding of the self-assembly of large-scale biological structures, which exist and function at and beyond the nanoscale. This mode of construction of nanoscale structures and nanosystems represents the so-called ‘bottom-up’ or ‘engineering-up’ approach to fabrication. Significant progress has been made in the development of nanoscience by transferring concepts found in the biological world into the chemical arena. The development of simple chemical systems that are capable of instructing their own organisation into large aggregates of molecules through their mutual recognition properties has been central to this success. By utilising a diverse array of intermolecular interactions as the information source for assembly processes, chemists have successfully applied biological concepts in the construction of complex nanoscale structures and superstructures with a variety of forms and functions. More recently, the utility of assembly processes has been extended through the realisation that recognition processes can be used to select a single structure from a library of equilibrating structures. These developments open the way for the design and implementation of artificial assembly processes that are capable of adapting themselves to the local environment in which they are conducted.

A New Method for the Synthesis of Aromatic Sulfurpentafluorides and Studies of the Stability of the Sulfurpentafluoride Group in Common Synthetic Transformations

Abstract A new synthesis of aromatic sulfurpentafluoride compounds is described. Subsequent elaboration of the aromatic rings in the presence of the sulfurpentafluoride group is also discussed for a variety of common synthetic methods. This paper also describes ab initio electronic structure calculations of 3- and 4-aminophenylsulfurpentafluoride, compared with 3- and 4-aminobenzotrifluoride, and presents X-ray crystal structures of two aromatic sulfurpentafluoride derivatives.

Minimal self-replicating systems

Examples of chemical systems capable of templating and catalysing their own synthesis—self-replicating systems—have begun to appear in the chemical literature over the last 15 years. For the biologist, these systems represent a link with the origin of life—their study can shed light on prebiotic chemical evolution. However, for the synthetic chemist, they represent the ultimate synthetic machine, capable of templating the production of a large number of perfect copies of themselves from a single original molecule. In this Review, we describe the design and synthesis of synthetic minimal replicating systems and provide a general overview and critique of the field.

Slippage—an alternative method for assembling [2]rotaxanes

The exploitation of size-complementarity between the macrocyclic component and the stoppers of the dumbbell component of a [2]rotaxane, together with stabilising noncovalent bonding interactions that create a thermodynamic trap, have permitted the development of an alternative method, which can be termed slippage, for the syntheses of [2]rotaxanes in good yields.

Integrating replication-based selection strategies in dynamic covalent systems.

In the past 15 years, the chemistry of reversible covalent bond formation (dynamic covalent chemistry (DCC)) has been exploited to engineer networks of interconverting compounds known as dynamic combinatorial libraries (DCLs). Classically, the distribution of library components is governed by their relative free energies, and so, processes that manipulate the free energy landscape of the DCL can influence the distribution of library members. Within the same time frame, the design and implementation of molecules capable of copying themselves--so-called replicators--has emerged from the field of template-directed synthesis. Harnessing the nonlinear kinetics inherent in replicator behavior offers an attractive strategy for amplification of a target structure within a DCL and, hence, engendering high levels of selectivity within that library. The instructional nature of replicating templates also renders the combination of replication and DCC a potential vehicle for developing complex reaction networks; a prerequisite for the development of the emerging field of systems chemistry. This Concept article explores the role of kinetically and thermodynamically controlled processes within different DCC frameworks. The effects of embedding a replicating system within these DCC frameworks is explored and the consequences of the different topologies of the reaction network for amplification and selectivity within DCLs is highlighted.

Complexation between methyl viologen (paraquat) bis(hexafluorophosphate) and dibenzo[24]crown-8 revisited.

Paraquat bis(hexafluorophosphate) undergoes stepwise dissociation in acetone. All three species-the neutral molecule, and the mono- and dications-are represented significantly under the experimental conditions typically used in host-guest binding studies. Paraquat forms at least four host-guest complexes with dibenzo[24]crown-8. They are characterized by both 1:1 and 1:2 stoichiometries, and an overall charge of either zero (neutral molecule) or one (monocation). The monocationic 1:1 host-guest complex is the most abundant species under typical (0.5-20 mM) experimental conditions. The presence of the dicationic 1:1 host-guest complex cannot be excluded on the basis of our experimental data, but neither is it unambiguously confirmed to be present. The two confirmed forms of paraquat that do undergo complexation-the neutral molecule and the monocation-exhibit approximately identical binding affinities toward dibenzo[24]crown-8. Thus, the relative abundance of neutral, singly, and doubly charged pseudorotaxanes is identical to the relative abundance of neutral, singly, and doubly charged paraquat unbound with respect to the crown ether in acetone. In the specific case of paraquat/dibenzo[24]crown-8, ion-pairing does not contribute to host-guest complex formation, as has been suggested previously in the literature.

Weak interactions in crystal engineering—understanding the recognition properties of the nitro group

1,3,5-Trinitrobenzene and 1,3,5-triethynylbenzene cocrystallise to form a solid state structure in which the two components assemble to form segregated hydrogen-bonded tapes. This behaviour is rationalised, through the use of the Cambridge Structural Database and ab initio electronic structure calculations, in terms of the fundamental recognition properties of the nitro group. The recognition behaviour of the nitro group is a function of both the intrinsic electronic properties of the nitro group itself and the nature of the hydrogen bond donor with which it interacts.

Recognition-mediated regiocontrol of a dipolar cycloaddition reaction

Abstract The rational design of a recognition-based system that is capable of accelerating and controlling the regiochemical outcome of a dipolar cycloaddition reaction between an azide and an alkyne is presented. The origins of the acceleration and control of the cycloaddition reactions are rationalized—using molecular mechanics calculations—in terms of the formation of a complex between the reagents which organizes and orients them prior to reaction.

Evolving Opportunities in Structure Solution from Powder Diffraction Data—Crystal Structure Determination of a Molecular System with Twelve Variable Torsion Angles

The genetic algorithm approach, in which a population of trial structures is allowed to evolve subject to well-defined procedures for mating, mutation, and natural selection, was employed to solve the complex molecular crystal structure of Ph2 P(O)(CH2 )7 P(O)Ph2 directly from powder diffraction data. The structure solution reveals an interesting (perhaps unexpected) molecular conformation (see picture), which emphasizes the importance of allowing complete conformational flexibility of the molecule in the structure solution calculation.

Manipulating replication processes within a dynamic covalent framework.

The reaction of an amine bearing an amidopyridine recognition site and an aldehyde bearing a carboxylic acid recognition site affords an imine that is capable of directing its own formation through a dynamic covalent replication cycle. Additionally, the amine, formed by reduction of the replicating imine, is a more efficient catalyst for the formation of the replicating imine than the imine is a catalyst for its own formation.