Self‐consistent field method for open‐shell systems within the density‐matrix functional theory

Abstract

The unrestricted Hartree-Fock method is extended to correlation calculation within the density-matrix functional theory. The method is derived from an entropic cumulant functional for the correlation energy. The eigenvalue equations for the spin-orbitals are modified by the orbital occupation numbers. The Euler equation for the occupation numbers results in the Fermi-Dirac distribution, which is very efficient to update as soon as the orbital eigenvalue equations are solved. The method is demonstrated on the ground state of O2$$ {}_2 $$.

Emergence of ATP‐ and GTP‐Binding Aptamers from Single RNA Sequences by Error‐Prone Replication and Selection

Emergence of ATP- and GTP-Binding Aptamers from Single RNA Sequences by Error-Prone Replication and Selection**

Function in RNA oligomers - specifically low μM specific binding of purine (ATP and GTP) nucleotides - can arise from single, non-functional and partially homopolymeric (polyA) sequences of minimal structural and informational complexity by iterative cycles of mutation and selection.


Abstract

The spontaneous emergence of function from diverse RNA sequence pools is widely considered an important transition in the origin of life. Here we show that diverse sequence pools are not a prerequisite for the emergence of function. Starting five independent selection experiments each from a single RNA seed sequence - comprising a central homopolymeric poly-A (or poly-U) segment flanked by different conserved primer binding sites - we observe transformation (continuous drift) of the seeds into low diversity sequence pools by mutation, truncation and recombination without ever reaching that of a random pool even after 24 rounds. Upon continuous error prone replication and selection for ATP binding we isolate specific ATP- or GTP-binding aptamers with low micromolar affinities. Our results have implications for early RNA evolution in the light of the high mutation rates associated with both non-enzymatic and enzymatic prebiotic RNA replication.

Elucidating the Mechanism of Freeze‐Thaw Driven Content Mixing between Protocells

Elucidating the Mechanism of Freeze-Thaw Driven Content Mixing between Protocells

Freeze-thaw cycles serve as physicochemical driving force for the lateral exchange of enclosed material between giant lipid vesicles. It was demonstrated that this exchange relies on transient periods of membrane permeability leading to content diffusion across vesicle membranes. Moreover, we explored and quantified essential parameters affecting the lateral transfer efficiency.


Abstract

Modern cells rely on highly evolved protein networks to accomplish essential life functions, including the inheritance of information from parents to their offspring. In the absence of these sophisticated molecular machineries, alternatives were required for primitive protocells to proliferate and disseminate genetic material. Recurring environmental constraints on ancient earth, such as temperature cycles, are considered as prebiotically plausible driving forces capable of shuffling of protocellular contents, thereby boosting compositional complexity. Using confocal fluorescence microscopy, we show that temperature oscillations such as freezing-thawing (FT) cycles promote efficient content mixing between giant unilamellar vesicles (GUVs) as model protocells. We shed light on the underlying exchange mechanism and demonstrate that transient periods of destabilized membranes enable the diffusion of cargo molecules across vesicle membranes. Furthermore, we determine essential parameters, such as membrane composition, and quantify their impact on the lateral transfer efficiency. Our work outlines a simple scenario revolving around inter-protocellular communication environmentally driven by periodic freezing and melting of water.

Influence of Silicate Rock Glass Compositions on the Efficacy of Prebiotic RNA Polymerization Reactions: The Case of 3’,5’ Cyclic Guanosine Monophosphate

Influence of Silicate Rock Glass Compositions on the Efficacy of Prebiotic RNA Polymerization Reactions: The Case of 3’,5’ Cyclic Guanosine Monophosphate

Glass composition matters: This work demonstrates that the outcome of dry-phase prebiotic polymerization reactions could have been strongly affected by the oxide composition of the hosting rock glasses.


Abstract

Silicate glasses are ubiquitous on terrestrial planets wherever molten rock – generated by volcanism or impacts – is quenched by air or water. Hence, they provided ready and abundant reactive solid surfaces for prebiotic chemistry on the early Earth. Here, we show that rock glass composition determines basicity, which in turn modulates the outcome of prebiotic synthetic processes such as the polymerization of 3’, 5’ cyclic guanosine monophosphate.

Front Cover: Elucidating the Mechanism of Freeze‐Thaw Driven Content Mixing between Protocells (ChemSystemsChem 5/2023)

Front Cover: Elucidating the Mechanism of Freeze-Thaw Driven Content Mixing between Protocells (ChemSystemsChem 5/2023)

The Front Cover illustrates the exchange of genetic material between model protocells through cycles of freezing and thawing. Freeze-thaw cycles as prebiotic environmental driver induce a transient increase in membrane permeability enabling the lateral transfer of genetic information in a population of primitive protocells. More information can be found in the Research Article by Benedikt Peter and Petra Schwille.


Molecular Engineering of Carbohydrate Recognition

Molecular Engineering of Carbohydrate Recognition

The recognition of carbohydrates has been of growing interest in the supramolecular chemistry field, with specific relevance for numerous potential applications. At the same time, the binding many of carbohydrates in water selectively and with high affinity still presents a number of practical challenges that inspire ongoing research efforts toward new classes of bio-inspired synthetic receptors.


Abstract

Carbohydrates play a number of structural, functional, and metabolic roles in underpinning natural life processes, acting in states of both health and disease. Given this importance, over millions of years of evolution, living systems have developed an ability to recognize and bind carbohydrates, achieving remarkable recognition affinity and specificity in spite of the often hydrophilic and ubiquitous character of carbohydrate targets. In recent years, bio-inspired synthetic receptors have been developed to bind carbohydrates, with examples of (pseudo)temple-shaped receptors, flexible receptors, and dynamic-covalent/coordinative receptors reported. Certain of these have even demonstrated promising results, for example in binding glucose or exhibiting antiviral and antibiotic function. Accordingly, and in spite of remaining challenges, the development of synthetic receptors for carbohydrate recognition holds great promise to combat some of the most urgent problems facing our world today.

Elucidating the Mechanism of Freeze‐Thaw Driven Content Mixing between Protocells

Elucidating the Mechanism of Freeze-Thaw Driven Content Mixing between Protocells

We show how recurring environmental constraints on ancient earth, namely cycles of freezing and thawing, might have driven the dissemination of genetic material in populations of primitive protocells. In this work, confocal fluorescence microscopy at sub-zero temperatures was used to gain mechanistic insights into inter-protocellular communication based on cyclic freezing and melting of the aqueous environment. The cover design highlights the transient formation of membrane pores that enable content diffusion across protocell membranes…” This and more about the story behind the front cover can be found in the Research Article at 10.1002/syst.202300008.


Abstract

The front cover artwork is provided by the Schwille group from the Max Planck Institute of Biochemistry in Martinsried. The image shows the dissemination of genetic material in a population of primitive protocells during freeze-thaw induced periods of membrane permeability. Read the full text of the Research Article at 10.1002/syst.202300008.

Dcalycinumines A–E, alkaloids with cytotoxic activities of nasopharyngeal carcinoma cells from Daphniphyllum calycinum

Comprehensive Summary

Five novel Daphniphyllum alkaloids, named dcalycinumines A–E (14, 6), and eight previously described Daphniphyllum alkaloids (5, 713) were isolated from Daphniphyllum calycinum. Compound 1 is the first Daphniphyllum alkaloid possessing a highly rearranged 6/6/6/7/5/6 hexacyclic architecture with a unique 3-methyl-1-azabicyclo [4,4,0] decane ring system. Compound 2 represents a rare diamino Daphniphyllum alkaloid with an unprecedented 6/5/5/6/6/5 carbon skeleton featuring a unique 1-aza-6-azaspiro [4,5] decane unit, whereas 3 also represents a rare diamino Daphniphyllum alkaloid as a possible precursor of 2. Compound 4 is the second example of C-22-nor yuzurimine-type alkaloids. Their structures and absolute configurations were elucidated by HRESIMS, NMR spectroscopic analyses, ECD calculations, and single-crystal X-ray diffraction. Moreover, compound 1 showed remarkable antitumor activities, which could inhibit the proliferation, migration and invasion of nasopharyngeal carcinoma cells, and promoted nasopharyngeal carcinoma cells apoptosis.

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Stereoselective Synthesis of Iminosugar‐C‐Glycosides through Addition of Organometallic Reagents to N‐tert‐Butanesulfinyl Glycosylamines: A Comprehensive Study

Stereoselective Synthesis of Iminosugar-C-Glycosides through Addition of Organometallic Reagents to N-tert-Butanesulfinyl Glycosylamines: A Comprehensive Study

A comprehensive study of the preparation and reactivity of N-tert-butanesulfinyl glycosylamines with simple Grignard and organo lithium reagents is reported. As they readily react as latent imine equivalents with a variety of carbon nucleophiles in batch and continuous flow chemistry, these carbohydrate derivatives constitute very useful precursors for the diastereoselective synthesis of bioactive compounds such as iminosugar-C-glycosides.


Abstract

A comprehensive study of the preparation and reactivity of N-tert-butanesulfinyl glycosylamines with simple Grignard and organo lithium reagents in batch vs. continuous flow chemistry is reported. As they readily react as latent imine equivalents with a variety of carbon nucleophiles, these carbohydrate derivatives constitute very useful precursors for the diastereoselective synthesis of bioactive compounds such as iminosugar-C-glycosides. A hybrid protocol, involving the addition of benzylmagnesium chloride to a (S R )-arabinofuranosylamine substrate in flow, at room temperature, combined with a cyclization protocol in batch is also described for the first time. Of note, this semi-continuous flow process shortens the synthesis of imino-C-glycoside scaffolds to a single workday.

Lewis Acid Catalysed Chemoselective Amination of Alcohols Using Heterocyclic Thiones: An Avenue to Thiotetrazole Derivatives

Lewis Acid Catalysed Chemoselective Amination of Alcohols Using Heterocyclic Thiones: An Avenue to Thiotetrazole Derivatives

Herein, the development of a Cu(OTf)2 catalysed chemoselective amination of alcohols using heterocyclic thiones is described. Notably, the method is additive, ligand or inert atmosphere free and shows good tolerance towards variety of alcohols and thiotetrazole derivatives affording good to excellent yields of the product.


Abstract

Herein,a protocol for the chemoselective formation of C−N bond using Cu(OTf)2 as catalyst has been described using heterocyclic thiones. The reaction occurs preferentially at the nitrogen centre over the sulphur atom leading to C−N bond formation. Water being the only by-product, the reaction is environmentally friendly. The reaction proceeds without any additive, ligand or inert atmosphere and shows good tolerance towards variety of alcohols and thiotetrazole derivatives. Our developed protocol could be scaled up to gram scale efficiently, which highlights the efficacy of this method and might offer potential application in synthetic industry.