Chiroptical Recognition of Carboxylates with Charge-Neutral Double-Stranded Zinc(II) Helicates.

Chirality analysis of small molecules for the determination of their enantiopurity is nowadays ruled by streamlined chromatographic methods which utilize chiral stationary phases. Chiroptical probes which rely on host-guest interactions are so far overshadowed by the latter but have the benefit of depending only on common spectroscopic techniques such as CD spectroscopy to distinguish enantiomers and to quantify their ratio. Interest into this receptor-based approach is constantly rising because non-invasive high-throughput screenings with a minimal waste production can be performed. In this study we investigate the possibility to utilize metal-based containers in form of charge-neutral helicates able to recognize anions for this purpose. Key building block of the helicates are triazole units which show rotational freedom and give rise to either a meso-structure or a racemic mixture of the right- and left-handed complex. A chiroptical response of the probe is observed upon recognition of chiral mono- or dicarboxylates and chirality analysis of tartrate is conducted by CD spectroscopy.

Orthogonal, modular anion-cation and cation-anion self-assembly using pre-programmed anion binding sites.

Subcomponent self-assembly relies on cation coordination whereas the roles of anions often only emerge during the assembly process. When sites for anions are instead pre-programmed, they have the potential to be used as orthogonal elements to build up structure in a predictable and modular way. We explore this idea by combining cation (M+) and anion (X-) binding sites together and show the orthogonal and modular build up of structure in a multi-ion assembly. Cation binding is based on a ligand (L) made by subcomponent metal-imine chemistry (M+ = Cu+, Au+) while the site for anion binding (X- = BF4 -, ClO4 -) derives from the inner cavity of cyanostar (CS) macrocycles. The two sites are connected by imine condensation between a pyridyl-aldehyde and an aniline-modified cyanostar. The target assembly [LM-CS-X-CS-ML],+ generates two terminal metal complexation sites (LM and ML) with one central anion-bridging site (X) defined by cyanostar dimerization. We showcase modular assembly by isolating intermediates when the primary structure-directing ions are paired with weakly coordinating counter ions. Cation-directed (Cu+) or anion-bridged (BF4 -) intermediates can be isolated along either cation-anion or anion-cation pathways. Different products can also be prepared in a modular way using Au+ and ClO4 -. This is also the first use of gold(i) in subcomponent self-assembly. Pre-programmed cation and anion binding sites combine with judicious selection of spectator ions to provide modular noncovalent syntheses of multi-component architectures.

A Charge-Neutral Self-Assembled L2Zn2 Helicate as Bench-Stable Receptor for Anion Recognition at Nanomolar Concentration.

The field of anion recognition chemistry is dominated by two fundamental approaches to design receptors. One relies on the formation of covalent bonds resulting in organic and often neutral host species, while the other one utilizes metal-driven self-assembly for the formation of charged receptors with well-defined nanocavities. Yet, the combination of their individual advantages in the form of charge-neutral metal-assembled bench-stable anion receptors is severely lacking. Herein, we present a fluorescent and uncharged double-stranded hydroxyquinoline-based zinc(II) helicate with the ability to bind environmentally relevant dicarboxylate anions with high fidelity in dimethyl sulfoxide (DMSO) at nanomolar concentrations. These dianions are pinned between zinc(II) centers with binding constants up to 145 000 000 M-1. The presented investigation exemplifies a pathway to bridge the two design approaches and combine their strength in one structural motif as an efficient anion receptor.

Hierarchically assembled helicates as reaction platform - from stoichiometric Diels-Alder reactions to enamine catalysis.

The stereoselectivity of a Diels-Alder reaction within the periphery of hierarchically assembled titanium(IV) helicates formed from mixtures of achiral, reactive and chiral, unreactive ligands was investigated in detail. Following the pathway of the chiral induction, the chiral ligands, solvents as well as substituents at the dienophile were carefully varied. Based on the results of the stoichiometric reaction, a secondary amine-catalyzed nitro-Michael reaction is performed as well which afforded reasonable diastereoselectivities.

Bimetallic Bis-anion Cascade Complexes of Magnesium in Nonaqueous Solution.

Bimetallic magnesium(II) complexes are gaining significant interest in catalysis, yet their fundamental formation and behavior in organic media remain surprisingly unexplored relative to other divalent cations. To understand key principles of their formation, we investigate symmetric ditopic ligands bearing a phenolic backbone and characterize their ability to form dinuclear magnesium(II) cascade complexes with two bridging anions. High-fidelity production of bimetallic magnesium complexes relative to the monometallic complexes is indicative of positive cooperativity. Binding and recognition of analytes or substrates is a key characteristic of metal cascade complexes and relies on anion exchange, but this is also rarely studied with bimetallic magnesium complexes. Investigations with acetate, phosphate, and pyrophosphate reveal exchange of bridging nitrates using the bis-dipicolylamine complex. Rare seven-coordinate magnesium centers are found for the ester complex. The findings in this study provide formative steps to establish design principles for future generations of bimetallic magnesium(II) complexes.

Stability of Hierarchically Formed Titanium(IV) Tris(catecholate ester) Helicates with Cyclohexyl Substituents in DMSO.

A cyclohexyl substituent strongly prefers the chair conformation with large substituents in equatorial positions, while other cycloalkyls are structurally more flexible. In hierarchically formed dimeric titanium(IV) tris(catecholates) equatorial versus axial connection of the cyclohexane to the ester results in either a more compact (axial) or more expanded (equatorial) structure. In DMSO solution the axial position results in a compact structure which minimizes solvophobic effects, leading to higher stability. However, computational investigations indicate that additionally intramolecular London dispersion interactions significantly contribute to the stability of the dimer. Thus, weak side-chain-side-chain interactions are responsible for the high stability of cyclohexyl ester derivatives with axial compared to equatorial ester connection.

Shedding Light on the Interactions of Hydrocarbon Ester Substituents upon Formation of Dimeric Titanium(IV) Triscatecholates in DMSO Solution.

The dissociation of hierarchically formed dimeric triple lithium bridged triscatecholate titanium(IV) helicates with hydrocarbyl esters as side groups is systematically investigated in DMSO. Primary alkyl, alkenyl, alkynyl as well as benzyl esters are studied in order to minimize steric effects close to the helicate core. The 1 H NMR dimerization constants for the monomer-dimer equilibrium show some solvent dependent influence of the side chains on the dimer stability. In the dimer, the ability of the hydrocarbyl ester groups to aggregate minimizes their contacts with the solvent molecules. Due to this, most solvophobic alkyl groups show the highest dimerization tendency followed by alkenyls, alkynyls and finally benzyls. Furthermore, trends within the different groups of compounds can be observed. For example, the dimer is destabilized by internal double or triple bonds due to π-π repulsion. A strong indication for solvent supported London dispersion interaction between the ester side groups is found by observation of an even/odd alternation of dimerization constants within the series of n-alkyls, n-Ω-alkenyls or n-Ω-alkynyls. This corresponds to the interaction of the parent hydrocarbons, as documented by an even/odd melting point alternation.

Kinetic investigation of the dissociation of dinuclear hierarchically assembled titanium(iv) helicates.

Hierarchically assembled helicates consisting of lithium-bridged triscatecholate titanium(iv) complexes represent a powerful self-assembled supramolecular system with applications as e.g. molecular balances for the evaluation of weak interactions, stereoselectivity switches in asymmetric synthesis or molecular switches. Their applications or properties are based on the monomer-dimer equilibrium which can be easily observed in solution. The dimer is the only species in the crystal. After dissolution, the dimer slowly dissociates into the monomer until the equilibrium is reached. This can be observed by NMR spectroscopy to investigate the kinetics of the dissociation process. A strong steric effect can be observed by studying differently substituted ligands. Activation energies of the dissociation process can be correlated with the size of the ester substituents and the system may be described as a molecular buckle.

From Hierarchical Helicates to Functional Supramolecular Devices.

Catechol ligands with aldehyde, ketone or ester groups attached in 3-position form, in the presence of titanium(IV) triscatecholate, titanium(IV) complexes. If lithium cations are the counterions, they can bind in a successive step to the salicylate units of the complex and form a dimeric triple-lithium-bridged dinuclear helicate. In solution, the dimer is in equilibrium with the monomer and the thermodynamics of the dimerization can be easily evaluated. Thus, the hierarchically assembled titanium(IV) helicates represent a lithium-dependent molecular switch. The investigation of different derivatives of the complex allows for an estimation of the influence of side chain functionalities on the energetics of the dimerization. Thus, the hierarchically assembled helicates can be used as a kind of molecular balance to determine weak interaction energies (solvophobic effects and even dispersive effects). In addition, tethering of two ligands leads to "classical" helicates. Removal or addition of lithium cations allows for a reversible switching between a compressed and expanded state, which in the case of chiral ligands can be even performed stereospecifically.

Chasing Weak Forces: Hierarchically Assembled Helicates as a Probe for the Evaluation of the Energetics of Weak Interactions.

London dispersion forces are the weakest interactions between molecules. Because of this, their influence on chemical processes is often low, but can definitely not be ignored, and even becomes important in cases of molecules with large contact surfaces. Hierarchically assembled dinuclear titanium(IV) helicates represent a rare example in which the direct observation of London dispersion forces is possible in solution even in the presence of strong cohesive solvent effects. Hereby, the dispersion forces do not unlimitedly support the formation of the dimeric complexes. Although they have some favorable enthalpic contribution to the dimerization of the monomeric complex units, large flexible substituents become conformationally restricted by the interactions leading to an entropic disadvantage. The dimeric helicates are entropically destabilized.

A Supramolecular Chiral Auxiliary Approach: "Remote Control" of Stereochemistry at a Hierarchically Assembled Dimeric Helicate.

Dimeric hierarchically-assembled titanium(IV) helicates are in solvent-dependent equilibrium with the corresponding monomers. Statistically formed mixtures of such complexes bearing chiral stereocontrolling ligands and achiral diene-substituted ligands show high diastereoselectivity and reasonable enantioselectivity in the Diels-Alder reaction with maleimides if the reaction proceeds with the dimer but not with the monomer. Thus, solvent dependent switching between the monomer and dimer enables on/off switching of the enantioselectivity.

N-heterocyclic carbene catalyzed synthesis of oxime esters.

A triazolium salt derived N-heterocyclic carbene catalyzes the redox esterification reaction between α-ß-unsaturated aldehydes and oximes. The resulting saturated oxime esters were obtained in very good yields for a broad range of aliphatic, aromatic and heteroaromatic substrates.