Advanced Chemistry Research Articles

Thiol-ene click chemistry: Enabling 3D printing of natural-based inks for biomedical applications

Over the last decade, 3D bioprinting has gained increasing popularity, being a technique capable of producing well-defined tissue-like structures. One of its most groundbreaking features is the ability to create personalized therapies tailored to the specific demands of individual patients. However, challenges including the selection of materials and crosslinking strategies, still need to be addressed to enhance ink characteristics and develop robust biomaterials. Herein, the authors showcase the potential of overcoming these challenges, focusing on the use of versatile, fast, and selective thiol-ene click chemistry to formulate inks for 3D bioprinting. The exploration of natural polymers, specifically proteins and polysaccharides, will be discussed and highlighted, outlining the advantages and disadvantages of this approach.Leveraging advanced thiol-ene click chemistry and natural polymers in the development of 3D printable bioinks may face the current challenges and is envisioned to pave the way towards innovative and personalized biomaterials for biomedical applications.

Responses of teachers in Scotland to the reintroduction of the practical project in the advanced higher chemistry curriculum

Abstract Many pupils who study chemistry in Scotland and intend to progress to university undertake a final capstone practical research project as part of their Advanced Higher chemistry qualification. This project work was suspended for several years due to COVID-19, then reintroduced in 2023/24. We surveyed 47 Scottish teachers during this first project year using a mixed-methods survey, and found that resource availability had the biggest impact on projects, with over half of respondents reporting that they asked pupils to buy materials and a third committing their own money. Technician support was seen as critical to success, but project selection was heavily curtailed by the availability of existing equipment or chemicals, even as teachers made good use of available professional development and other forms of support. We finally make recommendations around the resourcing of project work and teacher/technician CPD provision.

Few-femtosecond electron transfer dynamics in photoionized donor-π-acceptor molecules.

The exposure of molecules to attosecond extreme-ultraviolet (XUV) pulses offers a unique opportunity to study the early stages of coupled electron-nuclear dynamics in which the role played by the different degrees of freedom is beyond standard chemical intuition. We investigate, both experimentally and theoretically, the first steps of charge-transfer processes initiated by prompt ionization in prototype donor-π-acceptor molecules, namely nitroanilines. Time-resolved measurement of this process is performed by combining attosecond XUV-pump/few-femtosecond infrared-probe spectroscopy with advanced many-body quantum chemistry calculations. We show that a concerted nuclear and electronic motion drives electron transfer from the donor group on a sub-10-fs timescale. This is followed by a sub-30-fs relaxation process due to the probing of the continuously spreading nuclear wave packet in the excited electronic states of the molecular cation. These findings shed light on the role played by electron-nuclear coupling in donor-π-acceptor systems in response to photoionization.

Matching traditional Chinese medicine and western medicine-based research: Advanced nutraceutical development for proactive gastric cancer prevention.

Gastric cancer (GC), the third leading cause of cancer-related death globally, is complex and heterogeneous. This review explores multidisciplinary investigations of traditional Chinese medicine (TCM) combined with Western medical practices, emphasizing the development of nutraceuticals for cancer prevention. Using advanced analytical chemistry and food chemistry techniques, this study investigated how TCM components may be optimized for nutraceutical development. Focusing on molecular interactions with GC pathways, particularly the NF-κB, PI3K/Akt, and Wnt/β-catenin pathways, we examined the effects of TCM polyherbal formulas, extracts, and isolated compounds. These agents modulate apoptosis and cellular proliferation, underscoring their potential in preventive strategies. The convergence of nutraceutical and medicine food homology studies highlights a significant shift towards integrating TCM-derived compounds in a preventive health framework. This approach aims not only to enhance efficacy and reduce side effects but also to champion a preventive paradigm using personalized medicine to advance proactive health maintenance and disease prevention. The combination of TCM and western medical practices offers promising avenues for future research and practical applications in GC prevention.

Spin States Matter─from Fundamentals toward Synthetic Methodology Development and Drug Discovery.

ConspectusThe potent reactivity of carbenes and nitrenes has been traditionally harnessed by the employment of a transition-metal catalyst in which the reactivity of the metal carbene/nitrene intermediates can be controlled via the judicious tuning of the metal catalyst. In recent years, progress made in this research area has unveiled novel strategies to directly access free carbenes or nitrenes under visible-light-mediated conditions without the necessity of a metal catalyst for stabilization of the carbene/nitrene intermediate. Such photochemical approaches present new opportunities to leverage orthogonal reactions with classic metal-catalyzed transformations.In this Account, we describe the major contributions from our group over the past years pushing the boundaries of light-mediated carbene and nitrene transfer reactions. In the first section, the development from purely singlet carbene chemistry toward methods that allow access to triplet carbene intermediates will be dissected. We describe how the triplet spin state of reagents provides a rich array of novel synthetic methods that build on the fundamentals of spin conservation. We lay out the different strategies in accessing the triplet spin state of carbenes (i.e., via electronic stabilization, via triplet sensitization with suitable photocatalysts, or via exploitation of geometric features of these intermediates), followed by an analysis of how the triplet spin state can be employed to leverage reactions distinct to the classic singlet carbene chemistry.The second part focuses on free nitrene intermediates, whereby both photochemical and photocatalytic strategies are analyzed and compared. We initiate with a discussion of the reactivity of iminoiodinanes as nitrene precursors in the presence of a photocatalyst or under photochemical conditions and how these two approaches result in fundamentally distinct nitrogen-based intermediates. While a nitrene radical anion is formed under photocatalytic conditions, triplet nitrene is generated under photochemical conditions. We commence with an outline of the basic reactivity of nitrene transfer reactions under both conditions, with a focus on the reaction with substrates containing double bonds. Finally, the latest developments in advanced cycloaddition chemistry beyond classic aziridination reactions are examined, with a special emphasis on the relay of the triplet nitrene reactivity to enable a Pauson-Khand-like (2 + 2 + 1) cycloaddition reaction that offers convenient access to high value bioisosteres in drug discovery.The work from our group on spin-dependent reactivities offers insight into important fundamentals in synthesis, where the spin state of the reactive intermediate will dictate the reaction outcome. We hope this may inspire others to widen the scope of applications of light-mediated carbene and/or nitrene transfer reactions, and furthermore, we anticipate that these understandings may also enable the development of advanced catalytic systems featuring triplet metal carbene/nitrene intermediates.

Forte: A suite of advanced multireference quantum chemistry methods.

Forte is an open-source library specialized in multireference electronic structure theories for molecular systems and the rapid prototyping of new methods. This paper gives an overview of the capabilities of Forte, its software architecture, and examples of applications enabled by the methods it implements.

How Well Can Quantum Embedding Method Predict the Reaction Profiles for Hydrogenation of Small Li Clusters?

Quantum computing leverages the principles of quantum mechanics in novel ways to tackle complex chemistry problems that cannot be accurately addressed using traditional quantum chemistry methods. However, the high computational cost and available number of physical qubits with high fidelity limit its application to small chemical systems. This work employed a quantum-classical framework which features a quantum active space-embedding approach to perform simulations of chemical reactions that require up to 14 qubits. This framework was applied to prototypical example metal hydrogenation reactions: the coupling between hydrogen and Li2, Li3, and Li4 clusters. Particular attention was paid to the computation of barriers and reaction energies. The predicted reaction profiles compare well with advanced classical quantum chemistry methods, demonstrating the potential of the quantum embedding algorithm to map out reaction profiles of realistic gas-phase chemical reactions to ascertain qualitative energetic trends. Additionally, the predicted potential energy curves provide a benchmark to compare against both current and future quantum embedding approaches.

Modifications of Furan-Based Polyesters with the Use of Rigid Diols.

The replacement of polymers derived from petrochemical resources has been a prominent area of focus in recent decades. Polymers used in engineering materials must exhibit mechanical strength and stiffness while maintaining performance through a broad temperature range. Most of the polyesters used as engineering materials are based on terephthalic acid (TPA) and its derivatives, which provide necessary rigidity to molecular chains due to an aromatic ring. Bio-based alternatives for TPA-based polyesters that are gaining popularity are the polyesters derived from 2,5-furandicarboxylic acid (FDCA). To broaden applicational possibilities, one effective way to achieve specific properties in targeted applications is to adjust the composition and structure of polymers using advanced polymer chemistry techniques. The incorporation of rigid diols such as isosorbide, 1,4-cyclohexanedimethanol (CHDM), and 2,2,4,4-tetramethyl-1,3-cyclobutanediol (CBDO) should result in a greater stiffness of the molecular chains. This review extensively explores the effect of incorporating rigid diols on material properties through a review of research articles as well as patents. Moreover, this review mainly focuses on the polyesters and copolyesters synthesized via two-step melt polycondensation and its alterations due to the industrial importance of this method. Innovative synthesis strategies and the resulting material properties are presented.

Systematic Investigation of Dual-Target-Directed Ligands.

Multitarget-directed ligands (MTDLs) are compounds rationally designed to affect multiple targets, aiming for a better therapeutic profile. For over 20 years, MTDLs have garnered increasing attention, the idea being that their full potential would have been achieved, thanks to unprecedented target combinations and advanced medicinal chemistry strategies. This study presents a literature mining effort resulting in a data set of dual-target-directed ligands (DTDLs), the fundamental example of MTDLs. We used this data set to evaluate the rationale behind target selection and the chemical novelty of DTDLs targeting specific protein combinations. Our analysis focused on DTDL targets in terms of biological function, disease association, structure, and chemogenomic traits. We also compared DTDLs with single-target compounds. We found that well-known target pathology associations often guide DTDL design, leveraging existing chemical scaffolds and binding pocket similarities. These findings highlight the current state of the field and suggest substantial untapped potential for rational polypharmacology.

Understanding How Students Navigate An Upper-Year Science Laboratory Course In A Post-Pandemic Era

The scope of this preliminary study revolves around investigating the effectiveness of experiential learning in upper-year science laboratory courses in a post-pandemic era. In this study we have explored two key questions: 1. Can experiential learning facilitate independent inquiry in an upper-year undergraduate laboratory in a post-pandemic era? 2. Do incoming students feel prepared to carry out an in-person, hands-on, upper-year undergraduate laboratory experiments in a post-pandemic era? By exploring these questions through student reflections and perceptions in an advanced analytical chemistry inquiry-based laboratory course, we hope to acknowledge the impact the pandemic has had on first- and second-year foundational labs, and on the preparation of students for upper-year undergraduate labs. The shift towards virtual learning during the COVID-19 pandemic may have heavily impacted the development of core wet laboratory skills and thus made it challenging for students to build their confidence and skillset and attain success when challenged at a higher level.

Assessment of Innovative Technologies for Hazardous Waste Treatment and Remediation Review: A Sustainable Approach for Environmental Protection

<p>The management of hazardous waste is a critical environmental challenge that requires innovative and sustainable solutions to mitigate adverse impacts on ecosystems and human health. This research project aims to assess and evaluate cutting-edge technologies for the treatment and remediation of hazardous waste, focusing on their sustainability and effectiveness in environmental protection. The study will investigate various innovative methods such as advanced oxidation processes, bioremediation techniques, nanotechnology applications, and green chemistry strategies. These technologies offer promising opportunities to address hazardous waste contamination while minimizing resource consumption and environmental footprints. The research will include a comprehensive review of existing literature, case studies, and technical reports to gather insights into the performance, cost-effectiveness, and environmental benefits of these innovative technologies. Special emphasis will be placed on evaluating their applicability across different types of hazardous waste, ranging from industrial chemicals and pollutants to electronic waste and persistent organic pollutants. Furthermore, the study will analyze regulatory frameworks, policy implications, and socio-economic factors influencing the adoption and implementation of these technologies in diverse industrial sectors and geographical regions. Through rigorous assessment and analysis, this research aims to provide valuable insights and recommendations for stakeholders, policymakers, and environmental practitioners involved in hazardous waste management. The findings will contribute to advancing sustainable approaches for addressing hazardous waste challenges, promoting environmental protection, and fostering a circular economy mindset in waste management practices.</p>

Cyclization via Metal-Catalyzed Hydrogen Atom Transfer/Radical-Polar Crossover

AbstractCatalytic transformations of alkenes via the metal-hydride hydrogen atom transfer (MHAT) mechanism have notably advanced synthetic organic chemistry. This Account focuses on MHAT/radical-polar crossover (MHAT/RPC) conditions, offering a novel perspective on generating electrophilic intermediates and facilitating various intramolecular reactions. On using cobalt hydrides, the MHAT mechanism displays exceptional chemoselectivity and functional group tolerance, making it invaluable for the construction of complex biologically relevant molecules under mild conditions. Recent developments have enhanced regioselectivity and expanded the scope of MHAT-type reactions, enabling the formation of cyclic molecules via hydroalkoxylation, hydroacyloxylation, and hydroamination. Notably, the addition of an oxidant to traditional MHAT systems enables the synthesis of rare cationic alkylcobalt(IV) complexes, bridging radical mechanisms to ionic reaction systems. This Account culminates with examples of natural product syntheses and an exploration of asymmetric intramolecular hydroalkoxylations, highlighting the ongoing challenges and opportunities for future research to achieve higher enantioselectivity. This comprehensive study revisits the historical evolution of the MHAT mechanism and provides a groundwork for further innovations on the synthesis of structurally diverse and complex natural products.1 Introduction2 Intramolecular Hydroalkoxylation and Hydroacyloxylation Reactions3 Intramolecular Hydroamination Reactions4 Intramolecular Hydroarylation Reactions5 Deprotective Cyclization6 Asymmetric Intramolecular Hydroalkoxylation7 Conclusion

Molecular Environment Modulates CO2 Liberation from Carboxy-Biotin.

Carboxy-biotin serves as a coenzyme in certain carboxylases, exhibiting the remarkable capability to transfer a carboxy group to specific substrates. This process is made possible by the presence of biotin, a unique molecule that consists of a sulfur-containing tetrahydrothiophene ring fused to a ureido group. It is covalently attached to the enzyme via a flexible linker, allowing for its functionality. Biotin-dependent carboxylases consist of two distinct domains. The first domain (BC) facilitates biotin carboxylation by utilizing ATP, while the second domain (CT) transfers CO2 to the substrate. The process of ATP-dependent carboxylation using bicarbonate in the biotin carboxylase domain (BC) is well-known. However, the precise mechanism by which CO2 is released in the carboxyltransferase domain (CT) is still not fully understood. We employed advanced computational chemistry methods to investigate the decarboxylation process of carboxy-biotin in various molecular environments and different protonation states. Regardless of the polarity of the molecular surroundings, decarboxylation only occurs spontaneously in the protonated form. To determine the protonation state of biotin in different environments, we established an accurate computational chemistry method for calculating the pKa value of carboxy-biotin, reaching sub-kcal/mol accuracy. Based on our findings, nonpolar environments, such as the active site of the carboxyltransferase domain, have the ability to cause the spontaneous release of CO2 from carboxy-biotin. The CO2 release takes place spontaneously from protonated carboxy-biotin, promoting the carboxylation of substrates.

Accelerating ionizable lipid discovery for mRNA delivery using machine learning and combinatorial chemistry.

To unlock the full promise of messenger (mRNA) therapies, expanding the toolkit of lipid nanoparticles is paramount. However, a pivotal component of lipid nanoparticle development that remains a bottleneck is identifying new ionizable lipids. Here we describe an accelerated approach to discovering effective ionizable lipids for mRNA delivery that combines machine learning with advanced combinatorial chemistry tools. Starting from a simple four-component reaction platform, we create a chemically diverse library of 584 ionizable lipids. We screen the mRNA transfection potencies of lipid nanoparticles containing those lipids and use the data as a foundational dataset for training various machine learning models. We choose the best-performing model to probe an expansive virtual library of 40,000 lipids, synthesizing and experimentally evaluating the top 16 lipids flagged. We identify lipid 119-23, which outperforms established benchmark lipids in transfecting muscle and immune cells in several tissues. This approach facilitates the creation and evaluation of versatile ionizable lipid libraries, advancing the formulation of lipid nanoparticles for precise mRNA delivery.

Advances in the Synthesis of Bioorthogonal Reagents: s-Tetrazines, 1,2,4-Triazines, Cyclooctynes, Heterocycloheptynes, and trans-Cyclooctenes.

Aligned with the increasing importance of bioorthogonal chemistry has been an increasing demand for more potent, affordable, multifunctional, and programmable bioorthogonal reagents. More advanced synthetic chemistry techniques, including transition-metal-catalyzed cross-coupling reactions, C-H activation, photoinduced chemistry, and continuous flow chemistry, have been employed in synthesizing novel bioorthogonal reagents for universal purposes. We discuss herein recent developments regarding the synthesis of popular bioorthogonal reagents, with a focus on s-tetrazines, 1,2,4-triazines, trans-cyclooctenes, cyclooctynes, hetero-cycloheptynes, and -trans-cycloheptenes. This review aims to summarize and discuss the most representative synthetic approaches of these reagents and their derivatives that are useful in bioorthogonal chemistry. The preparation of these molecules and their derivatives utilizes both classical approaches as well as the latest organic chemistry methodologies.

Chemical composition and biological activities of essential oils and extract of Eucalyptus citriodora Hook

In this study, the leaves of Eucalyptus citriodora Hook (Lemon-Scented Eucalyptus) were harvested and collected from Üzümlü neighborhood of Fethiye district of Muğla in 2021. Chemical content analysis of steam distillation and hydrodistillation of essential oils were determined by GC-MS, while phenolic content of methanol extract was determined by HPLC-DAD. Antioxidant activities of essential oils and methanol extracts were determined by DPPH radical removal, ABTS cation removal, β-carotene linoleic acid, and CUPRAC activity methods; Anticholinesterase activity against AChE and BChE enzymes was determined by Ellman method; and tyrosinase inhibition associated with melanin hyperpigmentation, α-amylase inhibition, and α-glucosidase inhibition activities associated with diabetes were determined as an in vitro. The bioactivities and chemical contents of E. citriodora species, a great value of, Türkiye, were determined, bringing new natural products to organic chemistry. As a result of the study, new bioactive extracts would be obtained and thus, they can effectively reveal the potential of new business opportunities. Since methanol extract is effective against incurable diseases such as Alzheimer's and diabetes, it will also be possible to develop therapeutics of such diseases by investigating the advanced chemistry and in vivo activities of the extracts with new projects.

Scalable Approach to Molecular Motor-Polymer Conjugates for Light-Driven Artificial Muscles.

The integration of molecular machines and motors into materials represents a promising avenue for creating dynamic and functional molecular systems, with potential applications in soft robotics or reconfigurable biomaterials. However, the development of truly scalable and controllable approaches for incorporating molecular motors into polymeric matrices has remained a challenge. Here, it is shown that light-driven molecular motors with sensitive photo-isomerizable double bonds can be converted into initiators for Cu-mediated controlled/living radical polymerization enabling the synthesis of star-shaped motor-polymer conjugates. This approach enables scalability, precise control over the molecular structure, block copolymer structures, and high-end group fidelity. Moreover, it is demonstrated that these materials can be crosslinked to form gels with quasi-ideal network topology, exhibiting light-triggered contraction. The influence of arm length and polymer structure is investigated, and the first molecular dynamics simulation framework to gain deeper insights into the contraction processes is developed. Leveraging this scalable methodology, the creation of bilayer soft robotic devices and cargo-lifting artificial muscles is showcased, highlighting the versatility and potential applications of this advanced polymer chemistry approach. It is anticipated that the integrated experimental and simulation framework will accelerate scalable approaches for active polymer materials based on molecular machines, opening up new horizons in materials science and bioscience.

Understanding Defects in Amorphous Silicon with Million-Atom Simulations and Machine Learning.

The structure of amorphous silicon (a-Si) is widely thought of as a fourfold-connected random network, and yet it is defective atoms, with fewer or more than four bonds, that make it particularly interesting. Despite many attempts to explain such "dangling-bond" and "floating-bond" defects, respectively, a unified understanding is still missing. Here, we use advanced computational chemistry methods to reveal the complex structural and energetic landscape of defects in a-Si. We study an ultra-large-scale, quantum-accurate structural model containing a million atoms, and thousands of individual defects, allowing reliable defect-related statistics to be obtained. We combine structural descriptors and machine-learned atomic energies to develop a classification of the different types of defects in a-Si. The results suggest a revision of the established floating-bond model by showing that fivefold-bonded atoms in a-Si exhibit a wide range of local environments-analogous to fivefold centers in coordination chemistry. Furthermore, it is shown that fivefold (but not threefold) coordination defects tend to cluster together. Our study provides new insights into one of the most widely studied amorphous solids, and has general implications for understanding defects in disordered materials beyond silicon alone.

Understanding Defects in Amorphous Silicon with Million‐Atom Simulations and Machine Learning

AbstractThe structure of amorphous silicon (a‐Si) is widely thought of as a fourfold‐connected random network, and yet it is defective atoms, with fewer or more than four bonds, that make it particularly interesting. Despite many attempts to explain such “dangling‐bond” and “floating‐bond” defects, respectively, a unified understanding is still missing. Here, we use advanced computational chemistry methods to reveal the complex structural and energetic landscape of defects in a‐Si. We study an ultra‐large‐scale, quantum‐accurate structural model containing a million atoms, and thousands of individual defects, allowing reliable defect‐related statistics to be obtained. We combine structural descriptors and machine‐learned atomic energies to develop a classification of the different types of defects in a‐Si. The results suggest a revision of the established floating‐bond model by showing that fivefold‐bonded atoms in a‐Si exhibit a wide range of local environments–analogous to fivefold centers in coordination chemistry. Furthermore, it is shown that fivefold (but not threefold) coordination defects tend to cluster together. Our study provides new insights into one of the most widely studied amorphous solids, and has general implications for understanding defects in disordered materials beyond silicon alone.

Foundations of Quantum Information for Physical Chemistry.

Quantum information, a field in which great advances have been made in the past decades, now presents opportunities for advanced chemistry. One roadblock to progress, especially for experimental chemical science, is that new concepts and technical definitions need to be learned. In this paper, we review some basic, but sometimes misunderstood, concepts of quantum information based on the mathematical formulation of quantum mechanics that will be useful for chemists interested in discovering ways that chemistry can contribute to the quantum information field. We cover topics including qubits and their density matrix formalism, quantum measurement as a quantum operation, information theory, and entanglement. We focus on the difference between the concepts in the quantum context and the classic context. We also discuss the relation and distinction among entanglement, correlation, and coherence. We aim to clarify the rigorous definition of these concepts and then indicate some examples in physical chemistry.