Macrocyclic Precursor Research Articles

Rational Design of Diatomic Active Sites for Elucidating Oxygen Evolution Reaction Performance Trends

AbstractDiatomic catalysts, especially those with heteronuclear active sites, have recently attracted significant attention for their advantages over single‐atom catalysts in reactions with relatively high energy barrier, e.g. oxygen evolution reaction. Rational design and synthesis of heteronuclear diatomic catalysts are of immense significance but have so far been plagued by the lack of a definitive correlation between structure and catalytic properties. Here, we report macrocyclic precursor constrained strategy to fabricate series of transition metal (MT, Ni, Co, Fe, Mn, or Cu)‐noble (MN, Ir or Ru) centers in carbon material. One notable performance trend is observed in the order of Cu−MN<Mn−MN<Fe−MN<MN<Co−MN<Ni−MN. Meanwhile, the pathway has been not altered, still following the traditional adsorption reaction mechanism. The effect of the MT atoms on the performances could possibly originate from the distinct adsorption/desorption behaviors of key intermediates (i.e. *OH, *O and/or *OOH), strongly implying that ΔG*OOH–ΔG*OH could be used as the performance descriptor. We believe that our work provides useful strategy for synthesis of diatomic active sites with sole coordination configuration and varied composition, and in‐depth insight to their catalytic mechanism, which could be used for further optimization of diatomic catalysts towards oxygen electrocatalysis.

Rational Design of Diatomic Active Sites for Elucidating Oxygen Evolution Reaction Performance Trends.

Diatomic catalysts, especially those with heteronuclear active sites, have recently attracted significant attention for their advantages over single-atom catalysts in reactions with relatively high energy barrier, e.g. oxygen evolution reaction. Rational design and synthesis of heteronuclear diatomic catalysts are of immense significance but have so far been plagued by the lack of a definitive correlation between structure and catalytic properties. Here, we report macrocyclic precursor constrained strategy to fabricate series of transition metal (MT, Ni, Co, Fe, Mn, or Cu)-noble (MN, Ir or Ru) centers in carbon material. One notableperformance trend is observed in the order of Cu-MN < Mn-MN < Fe-MN < MN < Co-MN < Ni-MN. However, thepathway has been not altered, still following the traditional adsorption reaction mechanism. The effect of the MT atoms on theperformances could possibly originate from the distinct adsorption/desorption behaviors of key intermediates (i.e. *OH, *O and/or *OOH), strongly implying that ΔG*OOH-ΔG*OH could be used as the performance descriptor. We believe that our work provides useful strategy for synthesis of diatomic active sites with sole coordination configuration and varied composition, and in-depth insight to their catalytic mechanism, which could be used for further optimization of diatomic catalysts towards oxygen electrocatalysis.

How the macrocyclic precursors influence the M-N-C catalysts? Preparation and their applications on the electrochemically catalyzed hydrogen evolutions

Herein, a series of metallo-porphyrins, corroles and phthalocyanines were applied as the key precursors to confirm the influence of macrocyclic cores on the preparation of single- and dual-metal nitrogen-doped carbon (M-N-C) catalysts, and the control the M-N-C catalyst preparation towards accelerating electrocatalyzed hydrogen evolutions could be rationally modulated. Due to the synergetic effect, the dual-metal Co0.97Cu0.03TPP@rGO-900 M-N-C catalyst has the best performance on the electrochemically catalyzed hydrogen evolution with onset potentials as −166 mV and Tafel 117 mV·dec−1. More importantly, these M-N-C catalysts could also be used in a wide range of pH values, such as PBS and KOH medias.

A High‐Yielding Active Template Click Reaction (AT−CuAAC) for the Synthesis of Mechanically Interlocked Nanohoops

AbstractMechanically interlocked molecules (MIMs) represent an exciting yet underexplored area of research in the context of carbon nanoscience. Recently, work from our group and others has shown that small carbon nanotube fragments—[n]cycloparaphenylenes ([n]CPPs) and related nanohoop macrocycles—may be integrated into mechanically interlocked architectures by leveraging supramolecular interactions, covalent tethers, or metal‐ion templates. Still, available synthetic methods are typically difficult and low yielding, and general methods that allow for the creation of a wide variety of these structures are limited. Here we report an efficient route to interlocked nanohoop structures via the active template Cu‐catalyzed azide‐alkyne cycloaddition (AT−CuAAC) reaction. With the appropriate choice of substituents, a macrocyclic precursor to 2,2′‐bipyridyl embedded [9]CPP (bipy[9]CPP) participates in the AT−CuAAC reaction to provide [2]rotaxanes in near‐quantitative yield, which can then be converted into the fully π‐conjugated catenane structures. Through this approach, two nanohoop[2]catenanes are synthesized which consist of a bipy[9]CPP catenated with either Tz[10]CPP or Tz[12]CPP (where Tz denotes a 1,2,3‐triazole moiety replacing one phenylene ring in the [n]CPP backbone).

A High-Yielding Active Template Click Reaction (AT-CuAAC) for the Synthesis of Mechanically Interlocked Nanohoops.

Mechanically interlocked molecules (MIMs) represent an exciting yet underexplored area of research in the context of carbon nanoscience. Recently, work from our group and others has shown that small carbon nanotube fragments-[n]cycloparaphenylenes ([n]CPPs) and related nanohoop macrocycles-may be integrated into mechanically interlocked architectures by leveraging supramolecular interactions, covalent tethers, or metal-ion templates. Still, available synthetic methods are typically difficult and low yielding, and general methods that allow for the creation of a wide variety of these structures are limited. Here we report an efficient route to interlocked nanohoop structures via the active template Cu-catalyzed azide-alkyne cycloaddition (AT-CuAAC) reaction. With the appropriate choice of substituents, a macrocyclic precursor to 2,2'-bipyridyl embedded [9]CPP (bipy[9]CPP) participates in the AT-CuAAC reaction to provide [2]rotaxanes in near-quantitative yield, which can then be converted into the fully π-conjugated catenane structures. Through this approach, two nanohoop[2]catenanes are synthesized which consist of a bipy[9]CPP catenated with either Tz[10]CPP or Tz[12]CPP (where Tz denotes a 1,2,3-triazole moiety replacing one phenylene ring in the [n]CPP backbone).

A Platform Approach to Cleavable Macrocycles for the Controlled Disassembly of Mechanically Caged Molecules

AbstractInspired by interlocked oligonucleotides, peptides and knotted proteins, synthetic systems where a macrocycle cages a bioactive species that is “switched on” by breaking the mechanical bond have been reported. However, to date, each example uses a bespoke chemical design. Here we present a platform approach to mechanically caged structures wherein a single macrocycle precursor is diversified at a late stage to include a range of trigger units that control ring opening in response to enzymatic, chemical, or photochemical stimuli. We also demonstrate that our approach is applicable to other classes of macrocycles suitable for rotaxane and catenane formation.

A Platform Approach to Cleavable Macrocycles for the Controlled Disassembly of Mechanically Caged Molecules.

Inspired by interlocked oligonucleotides, peptides and knotted proteins, synthetic systems where a macrocycle cages a bioactive species that is "switched on" by breaking the mechanical bond have been reported. However, to date, each example uses a bespoke chemical design. Here we present a platform approach to mechanically caged structures wherein a single macrocycle precursor is diversified at a late stage to include a range of trigger units that control ring opening in response to enzymatic, chemical, or photochemical stimuli. We also demonstrate that our approach is applicable to other classes of macrocycles suitable for rotaxane and catenane formation.

Construction of hydrocarbon belts based on macrocyclic arenes.

Hydrocarbon belts have garnered significant attention due to their intriguing structures, unique properties, and potential applications in supramolecular chemistry and materials science. However, their highly inherently strained structures pose challenges in their synthesis, and the resulting tedious synthesis strategies hinder their large-scale applications. Utilizing unstrained macrocyclic arenes as precursors presents an efficient strategy, allowing for a strain-induction step that mitigates the energy barrier associated with building strain in the formation of these belts. Accessible unstrained macrocyclic precursors play a pivotal role in enabling efficient and large-scale syntheses of highly strained belts, facilitating their broader practical applications. This review provides an overview of the recent advancements in the construction of hydrocarbon belts using accessible macrocyclic arenes as building blocks. The synthetic strategies for these partially and fully conjugated hydrocarbon belts are discussed, along with their unique properties. We hope that this review will inspire the development of novel nanocarbon molecules, opening pathways for emerging areas and applications.

Nanographene with a Nitrogen-Doped Cavity.

Nitrogen-doped cavities are pervasive in graphenic materials, and represent key sites for catalytic and electrochemical activity. However, their structures are generally heterogeneous. In this study, we present the synthesis of a well-defined molecular cutout of graphene featuring N-doped cavity. The graphitization of a macrocyclic pyridinic precursor was achieved through photochemical cyclodehydrochlorination. In comparison to its counterpart with pyridinic nitrogen at the edges, the pyridinic nitrogen atoms in this nanographene cavity exhibit significantly reduced basicity and selective binding to Ag+ ion. Analysis of the protonation and coordination equilibria revealed that the tri-N-doped cavity binds three protons, but only one Ag+ ion. These distinct protonation and coordination behaviors clearly illustrate the space confinement effect imparted by the cavities.

Nanographene with a Nitrogen‐Doped Cavity

AbstractNitrogen‐doped cavities are pervasive in graphenic materials, and represent key sites for catalytic and electrochemical activity. However, their structures are generally heterogeneous. In this study, we present the synthesis of a well‐defined molecular cutout of graphene featuring N‐doped cavity. The graphitization of a macrocyclic pyridinic precursor was achieved through photochemical cyclodehydrochlorination. In comparison to its counterpart with pyridinic nitrogen at the edges, the pyridinic nitrogen atoms in this nanographene cavity exhibit significantly reduced basicity and selective binding to Ag+ ion. Analysis of the protonation and coordination equilibria revealed that the tri‐N‐doped cavity binds three protons, but only one Ag+ ion. These distinct protonation and coordination behaviors clearly illustrate the space confinement effect imparted by the cavities.

Active-metal template clipping synthesis of novel [2]rotaxanes.

Mechanically interlocked molecules (MIMs) have been important synthetic targets in supramolecular chemistry due to their beautiful structures and intriguing properties. We present herein a new synthetic strategy to access [2]rotaxanes, namely active-metal template clipping. We discuss the design of the target [2]rotaxanes, synthesis and characterization of the axle, macrocycle precursors and macrocycles as well as preparation of the final [2]rotaxanes by active template copper(I)-catalyzed alkyne-azide cycloaddition (CuAAC) as key step of the synthesis. HRMS and NMR experiments have been performed to confirm the formation of the interlocked structures.

Continuous-Flow Synthesis of Cycloparaphenylene Building Blocks on a Large Scale.

The synthesis of [n]cycloparaphenylenes ([n]CPPs) and similar nanohoops is usually based on combining building blocks to a macrocyclic precursor, which is then aromatized in the final step. Access to those building blocks in large amounts will simplify the synthesis and studies of CPPs as novel functional materials for applications. Herein, we report a continuous-flow synthesis of key CPP building blocks by using versatile synthesis techniques such as electrochemical oxidation, lithiations and Suzuki cross-couplings in self-built reactors on up-to kilogram scale.

Ultracycles consisting of macrocycles

Presented here is a one-pot strategy starting from rationally designed macrocyclic precursors for the diverse construction of sophisticated ultracycles. The type and amount of the base were found to significantly influence the macrocyclization outcome. The use of 4.0 equiv. CsF resulted in ultracycles of both types A and B while the presence of CsF larger than 6.0 equiv. produced only type B ultracycles. Existence of anion template increased the total yields and affected the distribution of the ultracycles. The ultracycles can accommodate large organic dicarboxylates anions via multiple anion–π and hydrogen bonds, and show selectivity to the size-matched heptanedioate (C72−). Based on all possible species and relevant equilibrium constants as well as material and charge balances, a numerical iterative algorithm was developed and applied to fit the association constants of B2H with dicarboxylates from glutarate (C52−) to octanedioate (C82−), which gave association constants up to 103 L/mol.

Synthesis and Chiroptical Properties of Binaphthyl‐Hinged [5]Helicenes

AbstractThe synthesis, structure, and circularly polarized luminescence (CPL) of two types of shape‐persistent [5]helicenes, hinged by a tethered (−OCH2CH2O−) or untethered (−OCH3) binaphthyl, are reported. The binaphthyl tethering system facilitated an effective Wittig ring‐closure reaction in the synthesis of a macrocyclic precursor, which could be easily converted to the title compound via successive photocyclization. The tethered groups were replaced with untethered −OCH3 groups by treatment with BBr3 followed by methylation. Both compounds exhibited similar spectra, and their longest wavelength absorption band with a low intensity was attributed to the transition from HOMO to LUMO+1. These compounds exhibited CPL with higher dissymmetry factors glum values than unlocked helicenes.

Synthesis of a Complex and Highly Potent PCSK9 Inhibitor.

The solution-based gram-scale synthesis of complex and highly potent proprotein convertase subtilisin-like/kexin type 9 (PCSK9) inhibitor 1 is presented. Construction of Northern fragment 2, followed by stepwise installation of Eastern 3, Southern 4, and Western 5 fragments, provided macrocyclic precursor 19. This intermediate was cross-linked via an intramolecular azide-alkyne click reaction, which preceded macrolactamization to afford the core framework of compound 1. Finally, coupling with poly(ethylene glycol) side-chain-based 6 gave the PCSK9 inhibitor 1.

Negatively curved molecular nanocarbons containing multiple heptagons are enabled by the Scholl reactions of macrocyclic precursors

•A general strategy for synthesizing negatively curved molecular nanocarbons •Remarkably curved π-backbones containing multiple heptagons •π-Backbones interlocked through both edge-to-face and face-to-face π-π interactions Embedding heptagons in polycyclic aromatic frameworks gives rise to negatively curved molecular nanocarbons, which not only are key fragments of long-sought-after carbon schwarzites but also bring new opportunities to explore unprecedented nanocarbons with interesting properties. This study demonstrates the Scholl reactions of macrocyclic precursors as a general strategy for synthesizing negatively curved molecular nanocarbons containing different numbers of heptagons. The π-backbones containing multiple heptagons are significantly curved and rigid, as revealed by density functional theory calculations and X-ray crystallography. Some of these negatively curved π-backbones are interlocked through both face-to-face and edge-to-face π-π interactions in the crystals. Such unusual π-π interactions have enabled a p-type organic semiconductor, although its hole mobility in the field effect transistors is limited by the amorphous nature of the vacuum-deposited films. Embedding heptagons in polycyclic aromatic frameworks gives rise to negatively curved molecular nanocarbons, which not only are key fragments of long-sought-after carbon schwarzites but also bring new opportunities to explore unprecedented nanocarbons with interesting properties. This study demonstrates the Scholl reactions of macrocyclic precursors as a general strategy for synthesizing negatively curved molecular nanocarbons containing different numbers of heptagons. The π-backbones containing multiple heptagons are significantly curved and rigid, as revealed by density functional theory calculations and X-ray crystallography. Some of these negatively curved π-backbones are interlocked through both face-to-face and edge-to-face π-π interactions in the crystals. Such unusual π-π interactions have enabled a p-type organic semiconductor, although its hole mobility in the field effect transistors is limited by the amorphous nature of the vacuum-deposited films.

Asymmetric Synthesis of Enantioenriched Zigzag-Type Molecular Belts by Kinetic Resolution and Subsequent Transformations

Asymmetric synthesis of enantioenriched zigzag-type molecular belts featuring copper/H8-binaphthol-catalyzed kinetic resolution of a resorcinarene derivative and subsequent transformations was developed. The acquired rigid and C4-symmetric belt exhibited remarkably enhanced photophysical and chiroptical properties in comparison to its conformationally fluxional macrocyclic precursor.

Synthesis of a Halicyclamine-Type Macrocyclic Scaffold via Biomimetic Transannular Cyclization

Previous attempts for biomimetic transannular reactions between two dihydropyrdine (DHP) rings incorporated in macrocycle frameworks relevant to manzamine alkaloids have been unsuccessful. Herein, we report an efficient regiocontrolled transannular cyclization of C2-symmetric macrocyclic precursor with rational modifications of the 3 and 6 positions of the DHP rings to synthesize a halicyclamine-type scaffold. The cis-double bonds installed in the macrocyclic alkyl loops played a crucial role in achieving the biomimetic transannular cyclization.

Single Atom Ring Contraction of Peptide Macrocycles Using Cornforth Rearrangement

AbstractSite‐selective transformations of densely functionalized scaffolds have been a topic of intense interest in chemical synthesis. Herein we have repurposed the rarely used Cornforth rearrangement as a tool to effect a single‐atom ring contraction in cyclic peptide backbones. Investigations into the kinetics of the rearrangement were carried out to understand the impact of electronic factors, ring size, and linker type on the reaction efficiency. Conformational analysis was undertaken and showed how subtle differences in the peptide backbone result in substrate‐dependent reaction profiles. This methodology can now be used to perform conformation‐activity studies. The chemistry also offers an opportunity to install building blocks that are not compatible with traditional C‐to‐N iterative synthesis of macrocycle precursors.

Single Atom Ring Contraction of Peptide Macrocycles Using Cornforth Rearrangement.

Site-selective transformations of densely functionalized scaffolds have been a topic of intense interest in chemical synthesis. Herein we have repurposed the rarely used Cornforth rearrangement as a tool to effect a single-atom ring contraction in cyclic peptide backbones. Investigations into the kinetics of the rearrangement were carried out to understand the impact of electronic factors, ring size, and linker type on the reaction efficiency. Conformational analysis was undertaken and showed how subtle differences in the peptide backbone result in substrate-dependent reaction profiles. This methodology can now be used to perform conformation-activity studies. The chemistry also offers an opportunity to install building blocks that are not compatible with traditional C-to-N iterative synthesis of macrocycle precursors.