ChemRxiv
Not a member yet
27047 research outputs found
Sort by
The amenability of different solvents to electrospray ionization mass spectrometry
No full textElectrospray ionization mass spectrometry is capable of transferring ions from solution to the gas phase across a broad range of solvents. A systematic investigation of the relative performance of different solvents has not been previously conducted, and we sought to remedy this situation. Fourteen solvents across a wide range of polarities were investigated for their ability to provide strong signals for four permanently charged ions. We found the best solvents to be acetone, acetonitrile, dichloromethane, tetrahydrofuran, and the previously unused (in an ESI-MS context) trifluorotoluene
(Supra-)Molecular Capsules
No full textStemming from early seminal notions of molecular recognition and encapsulation, three-dimensional, cavity-containing capsular compounds and assemblies have attracted intense interest due to the ability to modulate chemical and physical properties of species encapsulated within these confined spaces compared to bulk solution. With such a diverse range of covalent motifs and non-covalent (supramolecular) interactions available to assemble building blocks, an incredibly wide-range of capsular-type architectures have been developed. Furthermore, synthetic tunability of the internal environments gives chemists the opportunity to engineer systems for uses in sensing, sequestration, catalysis and transport of molecules, just to name a few. In this tutorial review, an overview is provided into the design principles, synthesis, characterisation, structural facets and properties of coordination cages, porous organic cages, supramolecular capsules and mechanically interlocked molecules. Using seminal and recent examples, the advantages and limitations of each system are explored, highlighting their application in various tasks and functions
Promiscuity guided evolution of a decarboxylative aldolase for synthesis of chiral tertiary alcohols
No full textEnzymes play an increasingly important role in synthetic biology and organic synthesis. Many potential applications benefit from promiscuous activity with a diverse array of substrates. Here, we show how to intentionally guide an enzyme towards generality through multi-generational directed evolution using substrate-multiplexed screening (SUMS). We demonstrate the advantages of promiscuity-guided evolution in a challenging context, engineering the decarboxylative aldolase UstD to perform a C-C bond forming reaction with ketone electrophiles. Mutations outside of the active site that impact catalytic function were immediately revealed by shifts in promiscuity, even when the overall activity was lower. By re-targeting these distal residues that couple to the active site with saturation mutagenesis, broadly activating mutations were readily identified. When analyzing active site mutants, SUMS identified both specialist enzymes that would have more limited utility as well as generalist enzymes with complementary activity on diverse substrates. These new UstD enzymes catalyze convergent synthesis of non-canonical amino acids bearing tertiary alcohol side chains. This methodology is easy to implement and enables the rapid and effective evolution of enzymes to catalyze desirable new functions
Salt-Free CatAnionic Vesicular Nanoreactor from Dithiocarbamate: Michael Addition of Nitroolefins in Aqueous Vesicle System
No full textThe salt-free CatAnionic vesicle was previously generated by mixing cationic and anionic amphiphiles, and removing the salt that occurred as a side product from the mixture. In this study, we report a new strategy to produce the salt-free CatAnionic vesicle of N,N-dialkylamonium N,N dialkyldithiocarbamate (AmDTC) through a one-step condensation between secondary amine and carbon disulfide. Both dialkylammonium cationic and dithiocarbamate anionic amphiphiles were generated concurrently during the condensation. The AmDTC was dispersed in water, resulting in the spontaneous formation of salt-free CatAnionic vesicles. Among several AmDTCs, the N,N-didodecylamonium N,N-didodecyldithiocarbamate (AmDTC-C12C12) showed high stability and was applied as a vesicular nanoreactor for the Michael addition in water. Michael addition in an aqueous system between nitroolefins and 1,3-dicarbonyl compounds afforded the desired twenty-three Michael adducts, with yields ranging from 65% to 92%. It is hypothesized that the AmDTC-C12C12 serves as a vesicular nanoreactor and plays a role in catalysis at the dithiocarbamate functional group. Preparative-scale and one-pot Michael addition by in situ generation of AmDTC-C12C12 vesicle afforded the Michael adducts also in good yields. The AmDTC-C12C12 vesicular nanoreactor was applied for the synthesis of (±)-baclofen with 54% yields over three steps. The reusability of the AmDTC-C12C12 was demonstrated and allowed the reuse of the CatAnionic vesicle up to seven cycles. Finally, chemical recycling was demonstrated by converting AmDTC-C12C12 to N,N-didodecylammonium chloride by simple acidification
Correcting Implicit Solvation at Metal/Water Interfaces Through the Incorporation of Competitive Water Adsorption
No full textConventional continuum solvation models are ubiquitous in computational catalysis, including for describing metal/water interfaces which are relevant to both solution-phase heterogeneous catalysis and electrocatalysis. Nonetheless, we find that such continuum models qualitative fail to describe both the adsorption free energy and conformational preference for many organic molecules at such interfaces, largely due to the failure of continuum models to incorporate the role of competitive water adsorption. We develop a simple phenomenological model that accounts for competitive water adsorption and show that the model, when used in conjunction with continuum solvation, provides a dramatic improvement in the description of both adsorption and conformational preference. The model is also extended to additionally incorporate the influence of applied potential at the electrode surface, thus facilitating computationally efficient applications to scenarios including electrocatalysis
Pellet dispensomixer and pellet distributor: Open hardware for nanocomposite space exploration via automated material compounding
No full textThe development of novel polymer-based nanocomposites necessitates the experimental preparation and characterization of numerous compositions to identify optimal formulations. For thermoplastic-based materials, the compounding process typically involves the labor-intensive tasks of dispensing, weighing, mixing, and extruding solid components such as polymers and additives. Herein, we present an open hardware solution that aims to automate this process. Our setup system is designed to streamline material surveying tasks associated with experimental design or closed-loop, self-driving laboratories. Our hardware setup consists of two main components: a multi-material pellet dispenser, which simplifies the preparation of targeted compositions from a range of master batches, and a pellet collector-distributor, which efficiently gathers and distributes processed materials into various containers throughout the experiment
Automatic orbital pair selection for multi-level local coupled-cluster based on orbital maps
No full textWe present an automatic, orbital-map based orbital pair selection scheme for multi-level local coupled-cluster approaches that exploits the locality of chemical reactions and concentrates on the part of the molecule directly involved in the reaction. The previously introduced pair-selected multi-level extension to domain-based local pair natural orbital coupled-cluster with singles, doubles, and semi-canonical perturbative triples [DLPNO-CCSD(T0)] partitions the orbital pairs according to relative changes in pair correlation energies [J. Chem. Phys. 157, 064102 (2022)]. To this end, maps between localized orbitals are required which in turn require maps between the atoms of structures along reaction paths. So far, these atom maps have been manually determined, which can be a (human) time-consuming procedure. In order to automatize this procedure, we present an atom mapping algorithm based on the principle of minimum chemical distance that incorporates the orientation through dihedral angles. Within the methodology of this algorithm, linear assignment problems are addressed and explicitly solved, giving rise to the idea of considering the orbital mapping problem as such. This led to a new strategy to obtain orbital maps that proves advantageous over the previously used direct orbital selection. Along with a modified orbital pair prescreening, this results in an improved variant of the pair-selected multi-level DLPNO-CCSD(T0) method. For given combinations of pair selection thresholds, the performance of this approach is demonstrated for various reaction types showing a significant efficiency gain and accurate results due to beneficial, systematic error cancellation. The presented method operates in a black-box manner due to its fully-automatized algorithms with only the need to specify a single target-accuracy parameter. Core orbitals can be included in the correlation treatment in a computationally cheap way such that there is no need for the frozen-core approximation. Additionally, we demonstrate that basis set extrapolation techniques can be applied. In this context, the approach shows deficiencies for the use of large basis sets, especially with diffuse basis functions, which can be traced back to the semi-canonical triples correction
Phononic Modulation of Spin-Lattice Relaxation in Molecular Qubit Frameworks
No full textThe advancement of molecular quantum information science demands solid-state integration of molecular electron spin qubits. With highly ordered structures and rational designability, microporous framework materials offer ideal matrices to host qubits. They exhibit tunable phonon dispersion relations and spin distributions, enabling optimization of essential qubit properties including the spin-lattice relaxation time (T1) and decoherence time. In this study, through spin dynamic and vibrational spectroscopic characterizations of two radical-embedded framework materials, we show that hydrogen-bonded networks give rise to a low Debye temperature of acoustic phonons and generates sub-terahertz optical phonons, both of which facilitate spin-lattice relaxation. Whereas deuterating hydrogen-bonded networks reduces both phonon frequencies and T1, eliminating such flexible structural motifs in the structure raises phonon dispersions and improves the T1 by one to two orders of magnitude. The phononic tunability of spin-lattice relaxation in molecular qubit frameworks would facilitate the development of solid-state qubits operating at elevated temperatures
A Facile Supramolecular Strategy to Switch Photodynamic Pathway and Augment ROS Production of Sensitizers for Enhanced Tumor Therapy
No full textThe photosensitizers (PSs) capable of generating radical reactive oxygen species (ROS) via the type-I electron transfer pathway under photoirradiation offer a promising solution to the challenge of unsatisfactory photodynamic therapy (PDT) in hypoxic environments. Classical PSs (type-II), however, primarily transfer excited energy to ground state O2 rather than undergoing photoinduced electron transfer, posing a tough challenge in promoting the type-I pathway through existing strategies. Herein, we demonstrate a novel and straightforward approach using bioinspired supramolecular assembly to convert classical type-II PSs into type-I supramolecular PSs with augmented ROS production. The phosphate-templated assembly facilitated the formation of nanoscale aggregates with orderly and efficient packing of PSs, effectively suppressing the energy transfer pathway by promoting photoinduced charge- separation between PSs (resulting in PS+· and PS−·), thereby enhancing the generation of superoxide radicals (O2−·) through electron transfer from PS−· to O2 (Scheme 1). Additionally, this shift of photosensitization pathway also enhances overall ROS production, overcoming the typical inhibition usually associated with PS aggregation and indicating the highly efficient ROS generation via the type-I pathway. Consequently, the type-I supramolecular PSs demonstrated excellent ROS generation capability in the treatment of hypoxic tumors, thus achieving outstanding therapeutic outcomes. This study not only addresses a critical challenge in PDT under hypoxic conditions but also opens a new avenue for modifying the sensitization behavior of clinically approved type-II PSs to achieve superior therapeutic outcomes
Identification of a novel transasparaginase activity of Bacillus Subtilis (bTG) for sequence-specific bioconjugation.
No full textThe ability of bacillus subtilis transglutaminase (bTG) to functionalize BSA has been investigated using peptide mapping experiments. Interestingly, the conjugation was not detected on a glutamine but on an asparagine residue. A sequence determination study was further performed and a sequence of ten amino acids for site specific conjugation was identified. A monobody showing no native reactivity with the bTG enzyme was produced with the identified peptide sequences and successfully conjugated to various types of substrates in very high yields (>90 %) with a 1/1/1.5 ratio of protein/amine/enzyme. Direct conjugation to the amino linker of a small interfering RNA (siRNA) was achieved in good yield and no impact on the siRNA activity was observed following the conjugation. The identified sequences were further engineered in VHH and IgG scaffolds and successful conjugation could also be observed with both small molecules and siRNA, confirming the potential of bTG for site-specific enzymatic bioconjugation