Deracemisations under kinetic and thermodynamic control

Deracemisation reactions occur when a racemic mixture is converted into a nonracemic mixture by increasing the quantity of one enantiomer at the expense of the other. This process can take place under thermodynamic control, but when combined with crystallisation processes kinetic factors also play a role. This review summarises the different approaches that have been taken to achieve efficient deracemisations. Starting from examples in which spontaneous symmetry breaking was found to occur, attrition enhanced deracemisation will be discussed in which solid-solution equilibria drive the deracemisation process. The combination of detailed experimental studies and mathematical models resulted in a profound understanding of this complex process, which is applicable to all congomerate forming compounds with a racemisable stereocenter. Then, we focus on deracemisations that occur under full thermodynamic control. Especially the combination of supramolecular interactions with a racemisation process gives interesting results, albeit that they are less predictable. The review will end with the possibilities supramolecular helical structures that show dynamic helicity can offer in conjunction with asymmetric catalysis. Herein, the helical preference induced by a minute amount of chiral compound is relayed to high enantiomeric excesses in a variety of reactions

Single-chain polymeric nanoparticles:Toward in vivo imaging and catalysis in complex media

\u3cp\u3eFolding an amphiphilic polymer around a transition metal affords homogeneous, water-soluble, and stable catalysts that are active in complex, cellular media. This chapter summarizes the progress made in this area over the last decade and explores how far research at the interface of polymer chemistry, homogeneous transition-metal-based catalysis, and disease biology can provide solutions to the treatment of complex diseases such as cancer. We start with a short overview on how single polymer chains can be constrained in their conformation by intramolecular covalent and noncovalent cross-linking processes. We then continue with discussing the compatibility of these folded/collapsed single polymer chains in and around cells. Because the stability and compatibility for these systems in water and complex media is promising, a number of biomedical applications are highlighted. First, gadolinium- and gallium-based folded polymers are attractive for magnetic resonance imaging and single-photon emission computerized tomography, respectively. In addition, folded polymers successfully serve as carriers for porphyrin-based systems that upon irradiation produce singlet oxygen, which is highly promising for photodynamic therapy. Moreover, folded polymers are also promising candidates for drug-carrier materials. Finally, examples are presented in which folded polymers operate as either carriers of reactive species or carriers of transition-metal-based catalysts to induce synthesis in living cells. The field of folded single-chain polymers is still young, and the examples discussed in this chapter highlight that many exciting challenges in the area of biomedical applications are awaiting. To successfully integrate current and future systems in complex cellular media, a seamless integration of the different disciplines is crucial.\u3c/p\u3

Cooperative folding of linear poly(dimethyl siloxane)s via supramolecular interactions

\u3cp\u3eThe synthesis and characterization of graft copolymers are reported based on linear poly(dimethyl siloxane) (PDMS) and chiral, pendant benzene-1,3,5-tricarboxamides (BTAs). The copolymers differ in degree of polymerization (DP) and BTA graft density. Characterization of the bulk materials at room temperature reveals that the BTAs aggregate in a helical fashion via threefold hydrogen-bond formation within the PDMS matrix. A significant degree of hydrogen bonding persists up to 180 °C, regardless of DP and BTA content. Analysis of the solution behavior by \u3csup\u3e1\u3c/sup\u3eH NMR spectroscopy indicates that BTA aggregation occurs in CDCl\u3csub\u3e3\u3c/sub\u3e, a solvent normally suppressing aggregation. Circular dichroism (CD) spectroscopy in 1,2-dichloroethane shows strong CD effects and reveals that increasing the DP and decreasing the BTA graft density results in an increase in the cooperativity of the BTA aggregation. Dynamic light scattering indicates the formation of particles with sizes of 400 nm. This is the first time that polymers with pendant BTAs show a sharp transition between a nonaggregated and aggregated state, a behavior similar to the one observed for “free” BTAs. The cooperative aggregation is attributed to the strong phase-segregation between the PDMS backbone and the BTAs, in combination with a high propensity of these polymers to form multichain aggregates.\u3c/p\u3

Benzene-1,3,5-tricarboxamide : a versatile ordering moiety for supramolecular chemistry

After their first synthesis in 1915 by Curtius, benzene-1,3,5-tricarboxamides (BTAs) have become increasingly important in a wide range of scientific disciplines. Their simple structure and wide accessibility in combination with a detailed understanding of their supramolecular self-assembly behaviour allow full utilization of this versatile, supramolecular building block in applications ranging from nanotechnology to polymer processing and biomedical applications. While the opportunities in the former cases are connected to the self-assembly of BTAs into one-dimensional, nanometer-sized rod like structures stabilised by threefold H-bonding, their multivalent nature drives applications in the biomedical field. This review summarises the different types of BTAs that appeared in the recent literature and the applications they have been evaluated in. Currently, the first commercial applications of BTAs are emerging. The adaptable nature of this multipurpose building block promises a bright future

Unravelling the pathway complexity in conformationally flexible N-centered triarylamine trisamides

Two families of C3-symmetrical triarylamine-trisamides comprising a triphenylamine- or a tri(pyrid-2-yl)amine-core are presented. Both families self-assemble in apolar solvents via cooperative hydrogen-bonding interactions into helical supramolecular polymers as evidenced by a combination of spectroscopic measurements, and corroborated by DFT calculations. The introduction of a stereocenter in the side chains biases the helical sense of the supramolecular polymers formed. Compared to other C3-symmetrical compounds, a much richer self-assembly landscape is observed. Temperature-dependent spectroscopy measurements highlight the presence of two self-assembled states of opposite handedness. One state is formed at high temperature from a molecularly dissolved solution via a nucleation-elongation mechanism. The second state is formed below room temperature through a sharp transition from the first assembled state. The change in helicity is proposed to be related to a conformational switch of the triarylamine core due to an equilibrium between a 3:0 and a 2:1 conformation. Thus, within a limited temperature window, a small conformational twist results in an assembled state of opposite helicity

Amplifying chiroptical properties of conjugated polymer thin-film using an achiral additive

\u3cp\u3eChiral conjugated polymers bearing enantiopure side chains offer the possibility to harness the effect of chirality in organic electronic devices. However, its use is hampered by the low degree of circular polarization in absorption (g\u3csub\u3eabs\u3c/sub\u3e) in most of the conjugated polymer thin-films studied. Here we demonstrate a versatile method to significantly increase the g\u3csub\u3eabs\u3c/sub\u3e by using a few weight percentages of a commercially available achiral long-chain alcohol as an additive. This additive enhances the chiroptical properties in both absorption and emission by ca. 5-10 times in the thin-films. We envisage that the alcohol additive acts as a plasticizer which enhances the long-range chiral liquid crystalline ordering of the polymer chains, thereby amplifying the chiroptical properties in the thin-film. The application of this methodology to various conjugated polymers has been demonstrated.\u3c/p\u3

Equilibrium model for supramolecular copolymerizations

The coassembly of different building blocks into supramolecular copolymers provides a promising avenue to control their properties and to thereby expand the potential of supramolecular polymers in applications. However, contrary to covalent copolymerization which nowadays can be well controlled, the control over sequence, polymer length, and morphology in supramolecular copolymers is to date less developed, and their structures are more determined by the delicate balance in binding free energies between the distinct building blocks than by kinetics. Consequently, to rationalize the structures of supramolecular copolymers, a thorough understanding of their thermodynamic behavior is needed. Though this is well established for single-component assemblies and over the past years several models have been proposed for specific copolymerization cases, a generally applicable model for supramolecular cooperative copolymers is still lacking. Here, we provide a generalization of our earlier mass-balance models for supramolecular copolymerizations that encompasses all our earlier models. In this model, the binding free energies of each pair of monomer types in each aggregate type can be set independently. We provide scripts to solve the model numerically for any (co)polymerization of one or two types of monomer into an arbitrary number of distinct aggregate types. We illustrate the applicability of the model on data from literature as well as on new experimental data of triarylamine triamide-based copolymers in three distinct solvents. We show that apart from common properties such as the degree of polymerization and length distributions, our approach also allows us to investigate properties such as the copolymer microstructure, that is, the internal ordering of monomers within the copolymers. Moreover, we show that in some cases, also intriguing analytical approximations can be derived from the mass balances

Single chain polymeric nanoparticles as selective hydrophobic reaction spaces in water

A Ru(II)-based catalyst trapped within an amphiphilic, folded polymer is employed for the oxidation of secondary alcohols to their corresponding ketones using tBuOOH as the oxidant. Under the applied catalytic conditions, the polymer catalyst forms a compartmentalized structure with a hydrophobic interior. We selected secondary alcohols that differ in hydrophobicity, reactivity, and steric hindrance as substrates, with the aim to elucidate how this affects the rate and the end conversion of the oxidation reaction. Our investigations show that the Ru(II)-based catalyst is very efficient for oxidation reactions in water. Moreover, high selectivity toward the more hydrophobic substrate is observed, which originates from the hydrophobic interior of the compartmentalized catalyst system. This hydrophobic selectivity is also observed in the reverse reaction, the transfer hydrogenation

Lipase-catalyzed ring-opening polymerizations of 4-substituted e-caprolactones : Mechanistic considerations

Lipase-catalyzed ring-opening polymerizations of 4-substituted -caprolactones employing Novozym 435 as the biocatalyst demonstrate dramatic differences in polymerization rates and selectivity depending on the size of the substituent. Quantification of the reaction rates shows that the polymerization rate decreases by a factor of 2 upon the introduction of a Me substituent at the 4-position. Moreover, 4-EtCL polymerizes 5 times slower than 4-MeCl and 4-PrCL is even 70 times slower. The decrease in polymerization rate is accompanied by a strong decrease in enantioselectivity: while the E-ratio of 4-MeCL polymerization is 16.9, the E-ratios of 4-EtCL and 4-PrCL are 7.1 and 2.0, respectively. Interestingly, Novozym 435 displays S-selectivity for 4-MeCL and 4-EtCL in the polymerization reaction, but the enantioselectivity is changed to the (R)-enantiomer in the case of the 4-PrCL. The nature of these differences was investigated by hydrolyzing all monomers in water/diisopropyl ether mixtures employing Novozym 435 as the catalyst. In the hydrolysis reactions, the rates are only moderately affected upon increasing the substituent size, and the enantioselectivity is S in all cases, also for 4-PrCL. Again, a steady decrease of the E-ratio was observed upon increasing the substituent size, but this was less pronounced than in the polymerization reactions: the E-ratios were 17.6, 12.4, and 4.6, going from 4-MeCL to 4-PrCL. For 4-substituted -caprolactones, the results obtained are a clear indication that the chirality of the propagating alcohol chain end is important in the catalytic cycle and that-in contrast to unsubstituted lactones-the rate-determining step is not necessarily the formation of the acyl-enzyme intermediate but more likely the deacylation of the acyl-enzyme intermediate by the propagating alcohol chain end

Single chain polymeric nanoparticles as compartmentalised sensors for metal ions

3,3'-Bis(acylamino)-2,2'-bipyridine substituted benzene-1,3,5-tricarboxamide (BiPy-BTA) grafted polynorbornene polymers were prepared via ring-opening metathesis polymerisation using a third generation Grubbs catalyst. The polymers fold intramolecularly via pi-pi interactions into fluorescent, compartmentalised particles of nanometer-size in mixtures of tetrahydrofuran and methylcyclohexane. Spectroscopic and light scattering techniques show that the compact conformation of the folded polymer is affected by increasing the BiPy-BTA functionalisation degree and by changing the solvent polarity. Changes in the conformation are accompanied by changes in the fluorescence intensity. Due to the affinity of the 2,2'-bipyridine units for metal ions such as copper, the particles obtained are effective sensors for these metals. The compartmentalisation of the binding motifs in SCPNs proves to be advantageous in sensor applications of these particles