RESUMEN

Fast and direct permeation of drug molecules is crucial for effective biotherapeutics. Inspired by a recent finding that fluorous compounds disrupt the hydrogen-bonded network of water, we developed fluoro-crown ether phosphate CyclicFP-X. This compound acts as a fast cell-permeating agent, enabling direct delivery of various bioactive cargos (X) into cancer cells without endocytic entrapment. In contrast, its nonfluorinated cyclic analog (CyclicP-X) failed to achieve cellular internalization. Although the acyclic fluorous analog AcyclicFP-X was internalized, this process occurred slowly owing to the involvement of an endocytic trapping pathway. Designed with a high fluorine density, CyclicFP-X exhibits compactness, polarity, and high-water solubility, facilitating lipid vesicle fusion by disrupting their hydration layers. Raman spectroscopy confirmed the generation of dangling -OH bonds upon addition of CyclicFP-OH to water. Furthermore, conjugating CyclicFP-X with fluorouracil (FU, an anticancer drug) via a reductively cleavable disulfide linker (CyclicFP-SS-FU) demonstrated the general utility of fluoro-crown ether phosphate as a potent carrier for biotherapeutics.

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RESUMEN

A three-component network for OFF/ON catalysis was built from a protonated nanoswitch and a luminophore. Its activation by addition of silver(i) triggered the proton-catalyzed formation of a biped and the assembly of a fast slider-on-deck (k 298 = 540 kHz).

RESUMEN

Boolean operations with multiple catalysts as output are yet unknown using molecular logic. The issue is solved using a two-component ensemble, composed of a receptor and rotaxane, which acts as a three-input AND gate with a dual catalytic output. Actuation of the ensemble gate by the stoichiometric addition of metal ions (Ag+ and Cd2+) and 2,2,2-trifluoroacetic acid generated in the (1,1,1) truth table state a catalyst duo that synergistically enabled a three-step reaction, furnishing a dihydroisoquinoline as the output of a three-input logic AND gate operation.

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RESUMEN

Driving conformational motion in defined off-equilibrium oscillations can be achieved using chemical fuels. When the ultrafast turnstile 1 (k298> 1012 Hz) was fueled with 2-cyano-2-phenylpropanoic acid (Fuel 1), the diprotonated rotor [H2(1)]2+ (k298 = 84.0 kHz) formed as a transient regaining the dynamics of the initial turnstile after consumption of the fuel (135 min). Upon addition of silver(I) (Fuel 2) to turnstile 1, the metastable rotor [Ag2(1)]2+ (k298 = 1.57 Hz) was initially furnished, but due to a consequentially triggered SN2 reaction, the Ag+ ions were consumed as insoluble AgBr along with regeneration of 1 (within 3 h). The off-equilibrium fast ⇆ slow rotor conversions fueled by acid and silver(I) were directly monitored by fluorescence and 1H NMR. In addition, metal ion exchange was fueled enabling off-equilibrium oscillations between rotors [Li2(1)]2+ ⇆ [Ag2(1)]2+. In the end, both sustainability and efficiency of the process were increased in unison by using the interfering proton waste in the formation of a [2]pseudorotaxane.

RESUMEN

The three-component nanorotor [Cu2(S)(R)]2+ (k298 = 46.0 kHz) that is a catalyst for a CuAAC reaction binds the click product at each of its copper centers thereby creating a new platform and a dynamic slider-on-deck system. Due to this sliding motion (k298 = 65.0 kHz) the zinc-porphyrin bound N-methylpyrrolidine is efficiently released into solution and catalyzes a follow-up Michael addition.

RESUMEN

Enzymes are encoded with a gamut of information to catalyze a highly selective transformation by selecting the proper reactants from an intricate mixture of constituents. Mimicking biological machinery, two switchable catalysts with differently sized cavities and allosteric control are conceived that allow complementary size-selective acyl transfer in an on/off manner by modulating the effective local concentration of the substrates. Selective activation of one of two catalysts in a mixture of reactants of similar reactivity enabled upregulation of the desired product.

RESUMEN

The dynamics of hydrogen bonding do not only play an important role in many biochemical processes but also in Nature's multicomponent machines. Here, a three-component nanorotor is presented where both the self-assembly and rotational dynamics are guided by hydrogen bonding. In the rate-limiting step of the rotational exchange, two phenolic O-H-N,N(phenanthroline) hydrogen bonds are cleaved, a process that was followed by variable-temperature 1 H NMR spectroscopy. Activation data (ΔG≠ 298 =46.7 kJ mol-1 at 298 K, ΔH≠ =55.3 kJ mol-1 , and ΔS≠ =28.8 J mol-1 K-1 ) were determined, furnishing a rotational exchange frequency of k298 =40.0 kHz. Fully reversible disassembly/assembly of the nanorotor was achieved by addition of 5.0 equivalents of trifluoroacetic acid (TFA)/1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) over three cycles.

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RESUMEN

The simple preparation of the multicomponent devices [Cu4 (A)2 ]4+ and [Cu2 (A)(B)]2+ , both rotors with fluxional axles undergoing domino rotation, highlights the potential of self-sorting. The concept of domino rotation requires the interconversion of axle and rotator, allowing the spatiotemporal decoupling of two degenerate exchange processes in [Cu4 (A)2 ]4+ occurring at 142 kHz. Addition of two equiv of B to rotor [Cu4 (A)2 ]4+ afforded the heteromeric two-axle rotor [Cu2 (A)(B)]2+ with two distinct exchange processes (64.0 kHz and 0.55 Hz). The motion requiring a pyridine→zinc porphyrin bond cleavage is 1.2×105 times faster than that operating via a terpyridine→[Cu(phenAr2 )]+ rupture. Finally, both rotors are catalysts due to their copper(I) content. The fast domino rotor (142 kHz) was shown to suppress product inhibition in the catalysis of the azide-alkyne Huisgen cycloaddition.

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A look at the elegance and efficiency of biological machines readily reveals that Nature masters the full gamut of chemical interactions to compose masterpieces of the living world. The present analysis singles out metal coordination for the actuation of nanomechanical motion. According to our analysis, metal coordination has a manifold of rewards, putting it primo loco in opportunities for putting nanomechanical systems into action: (i) its strength and dynamics can be properly modulated and fine-tuned by the choice of metal, redox state, and ligand(s), (ii) the high directionality of the interaction allows reliable design, and (iii) the emergence of novel self-sorting algorithms allows multiple of these interactions to be working in parallel. On top of all these advantages, intermolecular metal-ion translocation is a well-known factor in biological signaling. These benefits have recently proven their usefulness in the operation of networked devices and in overcoming the limitations of traditional stand-alone molecular systems.

RESUMEN

Different from the current paradigms of chemistry, a switchable catalytic system is presented that does not rely on a molecular switch in different toggling states but on a smart seven-component mixture that manages the reversible ON/OFF regulation of two catalytic processes. Hereunto, the workflow of two multicomponent rotary catalytic machineries was interlinked by the simultaneous shuffling of two components (metal and ligand) requiring perfect signaling in a 13-component system (see Movie 1). This network underwent reversible switching over three cycles as demonstrated by 1H NMR, UV-vis, and fluorescence spectroscopies and electrospray ionization mass spectrometry. Addition and removal of zinc(II) ions trigger three distinct events in parallel: the (i) mutually dependent self-assembly of three-component nanorotors and two-component reservoirs by resorting components, (ii) toggling between vastly different rotational exchange rates in the self-assembled rotors that directly affect catalysis, and (iii) toggling between two diverse catalytic reactions in a fully reproducible manner. Because of this information system, the concentrations of free aza-crown ether 7 and its complex with copper(I), that is, [Cu(7)]+, which represent the effective catalysts, are up- and downregulated in a manner to alternately switch ON/OFF a catalytic conjugate addition and a click reaction.

RESUMEN

Framework 1, a freely rotating turnstile, is transformed by sequential metal ion addition into the coordination-based double-minimum rotors [M2(1)]2n+ that operate at 8 kHz (M = Zn2+; n = 2) and 30 kHz (M = Cu+; n = 1). In a network with the fluorescent receptor 2, the metal ion exchange at [M2(1)]2n+ and thus indirectly the rotor speed is reported by distinct fluorescence changes at 2.

RESUMEN

A catalytically active three-component nanorotor is reversibly self-assembled and disassembled by remote control. When zinc(ii) ions (2 equiv.) are added as an external chemical trigger to the mixture of transmitter [Cu(1)]+ and pre-rotor assembly [(S)·(R)], two equiv. of copper(i) ions translocate from [Cu(1)]+ to the two phenanthroline sites of [(S)·(R)]. As a result, [Zn(1)]2+ forms along with the three-component assembly [Cu2(S)(R)]2+, which is both a nanorotor (k298 = 46 kHz, ΔH‡ = 49.1 ± 0.4 kJ mol-1, ΔS‡ = 9.5 ± 1.7 J mol-1 K-1) and a catalyst for click reactions (catalysis ON: A + B→AB). Removal of zinc from the mixture reverts the translocation sequence and thus commands disassembly of the catalytically active rotor (catalysis OFF). The ON/OFF catalytic cycle was run twice in situ in the full network.

RESUMEN

Three supramolecular slider-on-deck systems DS1-DS3 were obtained as two-component aggregates from the sliders S1-S3 and deck D with its three zinc porphyrin (ZnPor) binding sites. The binding of the two-footed slider to the deck varies with the donor qualities of and the steric hindrance at the pyridine/pyrimidine (pyr) feet, and was effected by two Npyr →ZnPor interactions. Accordingly, the sliders move over the three zinc porphyrins in the deck at different speeds, namely with 32.2, 220, and 440 kHz at room temperature. The addition of N-methylpyrrolidine as an organocatalyst to DS1-DS3 generates catalytic three-component machineries. By using a conjugate addition as a probe reaction, we observed a correlation between the operating speed of the slider-on-deck systems and the yields of the catalytic reaction. As the thermodynamic binding of the slider decreases, both the frequency of the sliding motion and the yield of the catalytic reaction increase.

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Two and a half decades of copper phenanthroline-based switches, devices and machines have illustrated the rich dynamic nature of these metal complexes. With an emphasis on the metal-ligand dissociation as the rate-determining step the present review summarizes not only spectacular examples of machinery, but also highlights rate data collected during a variety of investigations. Copper-ligand exchange reactions are mostly triggered by redox processes, addition of metal ions or addition of ligands. While the rate data spread over >8 orders of magnitude, individual effects of solvent, steric bulk, flexibility, σ-basicity and the trajectory (intra- vs. intermolecular dissociation) have large impact. Unfortunately, in many cases the exact mechanism in the rate-determining step (nucleophile-induced vs. monomolecular metal-ligand dissociation) has not been determined, suggesting to invest further efforts in the physical (in)organic chemistry of such coordination-driven systems.

RESUMEN

The fusion of two homoleptic complexes quantitatively created a novel three-component nanorotor. The intra-supramolecular rotational dynamics leads to a rapid exchange (k298 = 24.0 ± 2.5 kHz) of two degenerate Npy → ZnPor interactions. Metal exchange at the remote HETTAP complexation site provided a faster nanorotor (k298 = 34.0 ± 3.0 kHz).

RESUMEN

The nanomechanical switch 1 with its three orthogonal binding motifs-the zinc(II) porphyrin, azaterpyridine, and shielded phenanthroline binding station-is quantitatively and reversibly toggled back and forth between four different switching states by means of addition and removal of appropriate metal-ion inputs. Two of the four switching stages are able to initiate catalytic transformations (ON1, ON2), while the two others shut down any reaction (OFF1, OFF2). Thus, in a cyclic four-state switching process the sequential transformation A+B+C→AB+C→ABC can be controlled, which proceeds stepwise along the switching states OFF1→ON1 (click reaction: A+B→AB)→OFF2→ON2 (Michael addition: AB+C→ABC)→OFF1. Two consecutive cycles of the sequential catalysis were realized without loss in activity in a reaction system with eleven different components.