Julian Vogel

Membrane or no membrane? Fatty acids are valuable molecules to assemble prebiotic protocells. In this Minireview, two types of fatty acid-based compartments are compared: membrane-bound vesicles and membrane-free coacervates; the latter are shown to provide a promising alternative paradigm for prebiotic compartmentalization. It is also argued that the dynamic transition between fatty acid vesicles and coacervates offers an exciting new hypothesis for the emergence of the first living protocells.

Abstract

The prebiotic organization of chemicals into compartmentalized ensembles is an essential step to understand the transition from inert molecules to living matter. Compartmentalization is indeed a central property of living systems. Fatty acids represent the simplest prebiotic amphiphiles capable of self-assembling into membrane-bound vesicles, and have therefore emerged as valuable molecules to create models of protocellular compartments. Here, the main experimental findings supporting this idea are reviewed, together with approaches to increase the stability of fatty acid vesicles in adverse pH, salt, or temperature conditions. Recent studies on the self-assembly of fatty acids into membrane-free coacervate microdroplets are then discussed, providing a promising new paradigm for prebiotic compartmentalization. Lastly, it is also argued that the unique possibility of cycling between fatty acid vesicles and coacervates paves the way to an exciting new hypothesis for the emergence of the first living protocells.

A chemical system is presented where polymerization of peptide monomers results in predominantly macrocyclic oligomers. Using this system, we make a clear demonstration of how the combination of autocatalysis, diversity of products, and out-of-equilibrium conditions results in the selection of complex products.

Abstract

Autocatalytic reaction networks are instrumental for validating scenarios for the emergence of life on Earth and for synthesizing life de novo. Here, we demonstrate that dimeric thioesters of tripeptides with the general structure (Cys-Xxx-Gly-SEt)₂ form strongly interconnected autocatalytic reaction networks that predominantly generate macrocyclic peptides up to 69 amino acids long. Some macrocycles of 6–12 amino acids were isolated from the product pool and were characterized by NMR spectroscopy and single-crystal X-ray analysis. We studied the autocatalytic formation of macrocycles in a flow reactor in the presence of acrylamide, whose conjugate addition to thiols served as a model “removal” reaction. These results indicate that even not template-assisted autocatalytic production combined with competing removal of molecular species in an open compartment could be a feasible route for selecting functional molecules during the pre-Darwinian stages of molecular evolution.

A strategy by building cooperative anion–π interactions in a confined cage cavity to drive efficient and selective catalysis was established. Only 2 mol % of easily made chiral cages enabled excellent conversions and up to 97 % ee in catalyzing a class of decarboxylate Mannich reactions, which was unrealized with conventional organocatalysts.

Abstract

Exploiting anion–π interactions in catalyst design is a fascinating direction to develop new and fundamental catalysis. For the appealing yet flexible π-face activation, can two or more π-acidic surfaces be manipulated for cooperative activation to achieve efficient transformation and particularly selectivity control is highly desirable. Here, we demonstrate a supramolecular π-catalysis strategy by establishing cooperative π-face activation in a confined electron-deficient cage cavity. The catalysts have a triazine based prism-like cage core and pendant chiral base sites. Only 2 mol % of cage catalyst efficiently catalyzed the decarboxylate Mannich reactions of sulfamate-headed cyclic aldimines and a series of malonic acid half thioesters in nearly quantitative yields and up to 97 % ee, enabling an unprecedent organocatalytic approach. The supramolecular π-cavity is essential in harnessing cooperative anion–π interactions for the efficient activation and excellent selectivity control.

Nature Chemistry, Published online: 31 May 2021; doi:10.1038/s41557-021-00716-z

Statistical tools based on machine learning are becoming integrated into chemistry research workflows. We discuss the elements necessary to train reliable, repeatable and reproducible models, and recommend a set of guidelines for machine learning reports.

We demonstrated that the delicate mortise-and-tenon joint was precisely mimicked to construct a mechanically interlocked network (MIN), which simultaneously integrates incompatible mechanical adaptivity, robustness, and dynamic stability in a single system.

Abstract

Mortise-and-tenon joints have been widely used for thousands of years in wooden architectures in virtue of their artistic and functional performance. However, imitation of similar structural and mechanical design philosophy to construct mechanically adaptive materials at the molecular level is a challenge. Herein, we report a mortise-and-tenon joint inspired mechanically interlocked network (MIN), in which the [2]rotaxane crosslink not only mimics the joint in structure, but also reproduces its function in modifying mechanical properties of the MIN. Benefiting from the hierarchical energy dissipative ability along with the controllable intramolecular movement of the mechanically interlocked crosslink, the resultant MIN simultaneously exhibits notable mechanical adaptivity and structural stability in a single system, as manifested by decent stiffness, strength, toughness, and deformation recovery capacity.

The first nitrogen-doped aromatic belt with a [6]cycloparaphenylene skeleton ([6]CPP) was conveniently synthesized from calix[3]carbazole. The aromatic belt showed an enhanced π-conjugated structure and a deep cavity, and also exhibited strong green fluorescence and a narrow HOMO–LUMO energy gap.

Abstract

The design and synthesis of nitrogen-doped aromatic belts with conjugated structures still remain a challenge. Here, we report the first nitrogen-doped aromatic belt with a [6]cycloparaphenylene skeleton, which is conveniently synthesized from the easily available calix[3]carbazole. The aromatic belt has a rigid conjugated structure and deep cavity, and it can encapsulate one dichloromethane both in solution and in the solid state. Interestingly, the aromatic belt shows strong green fluorescence with a quantum yield of 0.39 and exhibits a narrow HOMO–LUMO energy gap of 2.02 eV. The belt-shaped conjugated structure composed of three carbazole subunits has specific optoelectronic properties that will promote wide applications in supramolecular chemistry and materials science.

Nonenzymatic copying of RNA templates with activated nucleotides is a useful model for studying the emergence of heredity at the origin of life. Previous experiments with defined-sequence templates have pointed to the poor fidelity of primer extension as a major problem. Here we examine the origin of mismatches during primer extension on random templates in the simultaneous presence of all four 2-aminoimidazole-activated nucleotides. Using a deep sequencing approach that reports on millions of individual template-product pairs, we are able to examine correct and incorrect polymerization as a function of sequence context. We have previously shown that the predominant pathway for primer extension involves reaction with imidazolium-bridged dinucleotides, which form spontaneously by the reaction of two mononucleotides with each other. We now show that the sequences of correctly paired products reveal patterns that are expected from the bridged dinucleotide mechanism, whereas those associated with mismatches are consistent with direct reaction of the primer with activated mononucleotides. Increasing the ratio of bridged dinucleotides to activated mononucleotides, either by using purified components or by using isocyanide-based activation chemistry, reduces the error frequency. Our results point to testable strategies for the accurate nonenzymatic copying of arbitrary RNA sequences.

Nature Chemistry, Published online: 15 April 2021; doi:10.1038/s41557-021-00671-9

Aromatic hydrocarbon belts consisting of fully fused benzenoid rings have fascinated scientists for over half a century. This Review revisits the protracted historical background of these compounds and features some recent breakthroughs in their rational design and synthesis, including the challenges faced in the precise synthesis of carbon-rich materials such as single-walled carbon nanotubes.

Multi-milligram-scale synthesis of the first example of a bowl-shaped nanographene with a pyrrolo-pyrrole core has been achieved via sequential, programmed, intramolecular direct arylations. This curved molecule possesses an inverse Stone–Thrower–Wales topology (a combination of fused pentagons and heptagons), small bowl-to-bowl inversion barrier, high-lying HOMO, weak red-emission at 615 nm, and a small dipole moment.

Abstract

A bowl-shaped nitrogen-doped nanographene composed of a pyrrolo[3,2-b]pyrrole core substituted with six arene rings circularly bonded with one another has been prepared via a concise synthetic strategy encompassing the multicomponent tetraarylpyrrolopyrrole (TAPP) synthesis, the Scholl reaction, and intramolecular direct arylation. This synthesis represents the first case of programmed sequential intramolecular direct arylation reactions utilizing the different reactivity of C–Br and C–Cl bonds. The target compound contains two central pentagons confined between two adjacent heptagons—the inverse Stone–Thrower–Wales topology. The presence of both five- and seven-membered rings in the final structure is responsible for interesting properties such as a perpendicularly aligned dipole moment, absorption and fluorescence in the orange-red region, weak emission originating from the charge-transfer character of a low-energy absorption band, and a high lying HOMO. In the solid state slipped convex-to-convex π–π stacking dominates.

Chemical fueling enables complex self‐replicating molecules to outcompete structurally simpler and faster replicators, revealing an important mechanism behind complexification that is required to transform chemistry into biology.

Abstract

Unravelling how the complexity of living systems can (have) emerge(d) from simple chemical reactions is one of the grand challenges in contemporary science. Evolving systems of self‐replicating molecules may hold the key to this question. Here we show that, when a system of replicators is subjected to a regime where replication competes with replicator destruction, simple and fast replicators can give way to more complex and slower ones. The structurally more complex replicator was found to be functionally more proficient in the catalysis of a model reaction. These results show that chemical fueling can maintain systems of replicators out of equilibrium, populating more complex replicators that are otherwise not readily accessible. Such complexification represents an important requirement for achieving open‐ended evolution as it should allow improved and ultimately also new functions to emerge.

Life is a non-equilibrium state of matter maintained at the expense of energy. Nature uses chemical energy stored in molecules to sustain non-equilibrium structures. This Review describes how chemical energy can be used to control the self-assembly of organic molecules. The ability of chemists to implement the described strategies in a synthetic context will permit the development of artificial systems with life-like properties.

Abstract

Life is a non-equilibrium state of matter maintained at the expense of energy. Nature uses predominantly chemical energy stored in thermodynamically activated, but kinetically stable, molecules. These high-energy molecules are exploited for the synthesis of other biomolecules, for the activation of biological machinery such as pumps and motors, and for the maintenance of structural order. Knowledge of how chemical energy is transferred to biochemical processes is essential for the development of artificial systems with life-like processes. Here, we discuss how chemical energy can be used to control the structural organization of organic molecules. Four different strategies have been identified according to a distinguishable physical-organic basis. For each class, one example from biology and one from chemistry are discussed in detail to illustrate the practical implementation of each concept and the distinct opportunities they offer. Specific attention is paid to the discussion of chemically fueled non-equilibrium self-assembly. We discuss the meaning of non-equilibrium self-assembly, its kinetic origin, and strategies to develop synthetic non-equilibrium systems.

Regioselective Scholl reactions have enabled successful synthesis of unprecedented zigzag carbon nanobelts, which present a wave‐like arrangement of hexagons in the unrolled lattice of (n,0) single wall carbon nanotubes (n=16 or 24). As monitored with fluorescence spectroscopy, one of these nanobelts binds C₆₀ with an association constant as high as (6.6±1.1)×10⁶ M⁻¹ in toluene.

Abstract

Zigzag carbon nanobelts are a long‐sought‐after target for organic synthesis. Herein we report new strategies for designing and synthesizing unprecedented zigzag carbon nanobelts, which present a wave‐like arrangement of hexagons in the unrolled lattice of (n,0) single wall carbon nanotubes (n=16 or 24). The precursors of these zigzag carbon nanobelts are hybrid cyclic arylene oligomers consisting of meta‐phenylene and 2,6‐naphthalenylene as well as para‐phenylene units. The Scholl reactions of these cyclic arylene oligomers form multiple carbon‐carbon bonds selectively at the α‐positions of naphthalene units resulting in the corresponding zigzag carbon nanobelts. As monitored with fluorescence spectroscopy, one of these nanobelts binds C₆₀ with an association constant as high as (6.6±1.1)×10⁶ M⁻¹ in the solution in toluene. Computational studies combining linear regression analysis and hypothetical homodesmotic reactions reveal that these zigzag nanobelts have strain in the range of 67.5 to 69.6 kcal mol⁻¹, and the ladderization step through Scholl reactions is accompanied by increase of strain as large as 69.6 kcal mol⁻¹. The successful synthesis of these nanobelts demonstrates the powerfulness and efficiency of Scholl reactions in synthesizing strained polycyclic aromatics.

Dimeric cycloparaphenylene (CPP) architectures with well‐defined flipping motion are constructed taking advantage of an efficient cyclocondensation reaction. Variable‐temperature nuclear magnetic resonance (VT‐NMR) analyses and theoretical calculations indicate rapid interconversion of cis and trans conformers at room temperature, while energetically favorable trans conformer exists at low temperature with the metastable cis conformer hidden. The trihexylsilylethynyl‐substituted dimer exhibits bright emission in solution at 616 nm with quantum yield up to 80%, representing the brightest CPP‐based emitter beyond 600 nm. A 1:2 host‐guest complex of the dimer and C60 is established with negative cooperativity, demonstrating the first example of 1:2 complex from CPP derivatives.

We propose a model for the replication of primordial protocell genomes that builds upon recent advances in the nonenzymatic copying of RNA. We suggest that the original genomes consisted of collections of oligonucleotides beginning and ending at all possible positions on both strands of one or more virtual circular sequences. Replication is driven by feeding with activated monomers and by the activation of monomers and oligonucleotides in situ. A fraction of the annealed configurations of the protocellular oligonucleotides would allow for template-directed oligonucleotide growth by primer extension or ligation. Rearrangements of these annealed configurations, driven either by environmental fluctuations or occurring spontaneously, would allow for continued oligonucleotide elongation. Assuming that shorter oligonucleotides were more abundant than longer ones, replication of the entire genome could occur by the growth of all oligonucleotides by as little as one nucleotide on average. We consider possible scenarios that could have given rise to such protocell genomes, as well as potential routes to the emergence of catalytically active ribozymes and thus the more complex cells of the RNA World.

Nature Chemistry, Published online: 14 December 2020; doi:10.1038/s41557-020-00594-x

A combination of metal- and anion-template synthesis directs the weaving of molecular weft and warp strands in the assembly of a 3 × 3 interwoven grid. Connection of the ligand strands by alkene metathesis produces the topology of a seven-crossing endless knot, an important cultural and religious symbol.

A highly strained carbon nanobelt (CNB) containing an octabenzo[12]cyclacene unit was synthesized and isolated in a single crystal form. It shows local aromaticity and highly shielded chemical environment in the cavity. Benzo‐annulation and phenyl substitution are crucial to the successful synthesis of this CNB.

Abstract

Synthesis of a carbon nanobelt (CNB) is a very challenging task in organic chemistry. Herein, we report the successful synthesis of an octabenzo[12]cyclacene based CNB (6), which can be regarded as a sidewall fragment of a (12,0) carbon nanotube. The key intermediate compound, a tetraepoxy nanobelt (5), was first synthesized by Diels–Alder reaction, and subsequent reductive aromatization gave the fully conjugated CNB 6. X‐ray crystallographic analysis unambiguously confirmed the belt‐shaped structure of 6. ¹H NMR spectrum and theoretical calculations (ACID, NICS, and 2D/3D ICSS) revealed localized aromaticity and stronger shielding chemical environment in the inner region of the belt. The optical properties (absorption and emission) of 6 were studied and correlated to its electronic structure. Strain analysis indicates that the phenyl substituents at the zigzag edges are crucial to the successful synthesis of 6. This report presents a new strategy towards highly strained CNBs.

Transient covalent bonds generated by chemical fuels are a fundamental tool for generating nonequilibrium reaction networks. In this Minireview, different approaches to transient bond formation are discussed, illustrating how similar fuel chemistry can be applied to a wide range of abiotic systems ranging from self-assembly to molecular machines.

Abstract

Biochemical systems accomplish many critical functions with by operating out-of-equilibrium using the energy of chemical fuels. The formation of a transient covalent bond is a simple but very effective tool in designing analogous reaction networks. This Minireview focuses on the fuel chemistries that have been used to generate transient bonds in recent demonstrations of abiotic nonequilibrium systems (i.e., systems that do not make use of biological components). Fuel reactions are divided into two fundamental classifications depending on whether the fuel contributes structural elements to the activated state, a distinction that dictates how they can be used. Reported systems are further categorized by overall fuel reaction (e.g., hydrolysis of alkylating agents, carbodiimide hydration) and illustrate how similar chemistry can be used to effect a wide range of nonequilibrium behavior, ranging from self-assembly to the operation of molecular machines.