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TiO2 Surface Hybridisation with Ag and CuO for Solar-Assisted Environmental Remediation and Sustainable Energy Applications
No full textIndustrialisation has led to unprecedented levels of outdoor air pollution, posing a significant health risk to human beings. Consequently, there is an urgent need to replace fossil fuels with sustainable energy sources, thereby mitigating these risks and providing a safer outdoor and indoor environment. Titanium dioxide is a versatile transition metal oxide with applications ranging from energy conversion to environmental remediation. However, it faces limitations, particularly in its absorption spectrum and charge separation efficiency, and enhancing these properties remains a significant challenge. In this research work, we have decorated the surface of TiO2 hybridising it with noble-metal and/or noble-metal oxides (Ag and/or CuxO) to improve the photocatalytic performances (monitoring the removal of nitrogen oxides and benzene, and hydrogen generation from water splitting) under simulated solar-light irradiation. Our results showed that titania modified with an Ag:Cu molar ratio equal to 1:1, not only exhibited the most promising performance in terms of nitrogen oxides and benzene removal, it was the optimum amount for the light-induced generation of hydrogen from water splitting
Light-Triggered Rolling and Unrolling of Molecular Crystal Microsheets
No full textThe anthracene derivative (E)-3-(3-(anthracen-9-yl)allylidene)-1,5-dioxaspiro[5.5]undecane-2,4-dione (E-ADUD) undergoes an EZ photoisomerization in solution but is inactive when crystals are grown using standard methods like solvent diffusion. However, the lipophilic cyclohexyl group facilitates precipitation of crystalline microsheets with submicron thicknesses from an aqueous solution containing sodium dodecyl sulfate and 1-dodecanol. These microsheets have horizontal dimensions on the order of 200 m and are composed of a metastable crystal polymorph that permits the EZ isomerization to proceed. EZ photoisomerization using visible light caused these microsheets to rapidly roll up into multilayer micro-cylinders with diameters ranging from 20-40 m. If the light was removed at this point, the microscrolls were stable indefinitely. Continued exposure to visible light uncurled these cylindrical structures, reversing the mechanical process but not the photochemical reaction. The unrolled microsheets retained their crystallinity and could bend and twist under alternating UV and visible light, behaving as a photoreversible crystal but without additional rolling up. The initial high curvature rolling up can be attributed to the creation of a surface layer of Z-isomer, while prolonged irradiation distributes this photoproduct more uniformly throughout the crystal and relieves the interfacial stress. This photoinduced rolling and unrolling could prove useful for applications like antenna or stent opening in hard-to-reach environments
Microbially derived P=S and P=Se bond formation
No full textMicrobial metabolism is a diverse and sustainable source of synthetic reagents that can be programmed for controlled and high-level production via synthetic biology. However, despite the chemical diversity of metabolism, the chemical utility of metabolites, and the available tools to control metabolic chemistry, there remain few examples of the use of cellular metabolites directly for chemical synthesis. Herein we report that diverse bacteria perform P=S bond formation (Ph3P to Ph3PS) via central sulfur metabolism and non-enzymatic chemistry in vivo and can also be applied to effect microbial P=Se bond formation (Ph3PSe). To the best of our knowledge, this is the first biochemical and genetic investigation of P=S bond formation in a microbial cell and the first use of microbial metabolites for P=Se bond formation in chemical synthesis
CoLiNN: A Tool for Fast Chemical Space Visualization of DNA-Encoded Libraries Without Enumeration
No full textVisualization of the combinatorial library chemical space provides a comprehensive overview of available compound classes, their diversity, and physicochemical property distribution - key factors in drug discovery. Typically, this visualization requires time- and resource-consuming compound enumeration, standardization, descriptor calculation, and dimensionality reduction. In this study, we present the Combinatorial Library Neural Network (CoLiNN) designed to predict the projection of compounds on a 2D chemical space map using only their building blocks and reaction information, thus eliminating the need for compound enumeration. Trained on 2.5K virtual DNA-Encoded Libraries (DELs), CoLiNN demonstrated high predictive performance, accurately predicting the compound position on Generative Topographic Maps (GTMs). GTMs predicted by CoLiNN were found very similar to the maps built for enumerated structures. In the library comparison task, we compared the GTMs of DELs and the ChEMBL database. The similarity-based DELs / ChEMBL rankings obtained with “true” and CoLiNN predicted GTMs were consistent. Therefore, CoLiNN has the potential to become the go-to tool for combinatorial compound library design – it can explore the library design space more efficiently by skipping the compound enumeration
Chemical Exchange in Unstable Emulsions
No full textNuclear magnetic resonance (NMR) is a routine method to study chemical exchange in reactions and molecular rearrangements in solution. However, when it comes to exchange of molecular species in liquid-liquid, two phase systems like in phase-transfer catalysis, the rate becomes a function of the surface between two phases, which means that only stable emulsions could be studied with standard equipment. Here, a setup is described with which unstable emulsions can be produced and studied in-situ by solution NMR spectroscopy. The setup provides sufficient torque and spinning frequency for generating an unstable two-phase water/oil mixture by rapid stirring. The pneumatically driven stirrer in the probe head was designed using ideas borrowed from magic angle sample spinning and a prototype was produced by 3D printing. As proof of concept, the dynamics in an aniline water emulsion over the phase boundary are studied by regular exchange spectroscopy NMR experiments
Affinity-Based Covalent Sialyltransferase Probes Enabled by Ligand-Directed Chemistry
No full textSialyltransferases (ST) are enzymes found in among others mammals and bacteria that are responsible for producing sialylated glycans, which are known to play important roles in human health and disease. An example of the latter being the opportunistic molecular mimicry by pathogenic bacteria. However, chemical tools to study sialyltransferases have been limited to non-covalent inhibitors and probes that do not allow isolation and profiling of these important enzymes. Here we report the first ever covalent probes for ST by utilising ligand-directed chemistry. These affinity-based probes are armed with a simple to synthesise but robust O-nitrobenzoxadiazole (O-NBD) warhead, which is a lysine specific SNAr electrophilic warhead with a desirable turn-on fluorescence property. We demonstrate their high specificity when applied to label both recombinant sialyltransferases as well as native lipooligosaccharide sialyltransferase (Lst) in Neisseria gonorrhoeae, a relevant human pathogen. This new class of modular covalent ST probes, and their future iterations, could pave the way for new detailed studies of sialyltransferases in their native environment
Isolation and electronic structures of lanthanide(II) bis(trimethylsilyl)phosphide complexes
No full textWhilst lanthanide (Ln) silylamide chemistry is mature, the corresponding silylphosphide chemistry is underdeveloped, with [Sm{P(SiMe3)2}{μ-P(SiMe3)2}3Sm(THF)3] being the sole example of a structurally authenticated Ln(II) silylphosphide complex. Here we expand Ln(II) {P(SiMe3)2} chemistry through the synthesis and characterization of nine novel complexes. The dinuclear ‘ate’ salt-occluded complexes [{Ln[P(SiMe3)2]3(THF)}2(μ-I)K3(THF)] (1-Ln; Ln = Sm, Eu) and polymeric ‘ate’ complex [KYb{P(SiMe3)2}3{μ-K[P(SiMe3)2]}2] (2-Yb) were prepared by the respective salt metathesis reactions of parent [LnI2(THF)2] (Ln = Sm, Eu, Yb) with 2 or 3 eq. of K{P(SiMe3)2} in diethyl ether. The separate treatment of these complexes with either pyridine or 18-crown-6 led to the formation of the mononuclear solvated adducts, trans-[Ln{P(SiMe3)2}2(py)4] (3-Ln; Ln = Sm, Eu, Yb) and [Ln{P(SiMe3)2}2(18-crown-6)] (4-Ln; Ln = Sm, Eu, Yb), with concomitant loss of K{P(SiMe3)2}. The complexes were characterized by a combination of NMR, EPR, ATR-IR, electronic absorption and emission spectroscopies, elemental analysis, SQUID magnetometry, and single crystal X-ray diffraction. We find that these complexes exhibit electronic structures that contrast with those of related Ln(II) bis(trimethylsilyl)amide complexes due to differences in ligand donor atom hardness and ligand steric requirements from Ln–P bonds being longer than Ln–N bonds
Seeing Double: Experimental Insights into the Formation, Reactivity, and Crosstalk of Thionitrite (SNO–) and Perthionitrite (SSNO–)
No full textHydrogen sulfide (H2S) and nitric oxide (NO) are important gaseous biological signaling molecules that are involved in complex cellular pathways. A number of physiological processes require both H2S and NO, which has led to the proposal that different H2S/NO• crosstalk species, including thionitrite (SNO–) and perthionitrite (SSNO–), are responsible for this observed codependence. Despite the importance of these S/N hybrid species, the reported properties and characterization, as well as the fundamental pathways of formation and subsequent reactivity, remain poorly understood. Herein we report new experimental insights into the fundamental reaction chemistry of pathways to form SNO– and SSNO–, including mechanisms for proton-mediated interconversion. In addition, we demonstrate new modes of reactivity with other sulfur-containing potential crosstalk species, including carbonyl sulfide (COS)
Navigating Ultra-Large Virtual Chemical Spaces with Product-of-Experts Chemical Language Models
No full textUltra-large virtual chemical spaces have emerged as a valuable resource for drug discovery, providing access to billions of make-on-demand compounds with high synthetic success rates. Chemical language models can potentially accelerate the exploration of these vast spaces through direct compound generation. However, existing models are not designed to navigate specific virtual chemical spaces and often overlook synthetic accessibility. To address this gap, we introduce product-of-experts (PoE) chemical language models, a modular and scalable approach to navigating ultra-large virtual chemical spaces. This method allows for controlled compound generation within a desired chemical space by combining a prior model pre-trained on the target space with expert and anti-expert models fine-tuned using external property-specific datasets. We demonstrate that the PoE chemical language model can generate compounds with desirable properties, such as those that favorably dock to the dopamine receptor D2 (DRD2) and are predicted to cross the blood-brain barrier (BBB), while ensuring that the majority of generated compounds are present within the target chemical space. Our results highlight the potential of chemical language models for navigating ultra-large virtual chemical spaces, and we anticipate that this study will motivate further research in this direction. The source code and data are freely available at https://github.com/shuyana/poeclm/
De Novo Synthesis and Structural Elucidation of CDR-H3 Loop Mimics
No full textThe binding affinity of antibodies to specific antigens stems from a remarkably broad repertoire of hypervariable loops known as complementarity-determining regions (CDRs). While recognizing the pivotal role of the heavy-chain 3 CDRs (CDR-H3s) in maximizing antibody-antigen affinity and specificity, the key structural determinants responsible for their adaptability to diverse loop sequences, lengths, and non-canonical structures are hitherto unknown. To address this question, we achieved a de novo synthesis of bulged CDR-H3 mimics excised from their full antibody context. CD and NMR data revealed that these stable standalone -hairpin scaffolds are well-folded and retain many of the native bulge CDR-H3 features in water. In particular, the tryptophan residue highly conserved across CDR-H3 sequences was found to extend the kinked base of these -bulges through a combination of stabilizing intramolecular hydrogen bond and CH/ interaction. The structural ensemble consistent with our NMR observations exposed the dynamic nature of residues at the base of the loop, suggesting that -bulges act as molecular hinges connecting the rigid stem to the more flexible loops of CDR-H3s. We anticipate that this deeper structural understanding of CDR-H3s will lay the foundation to inform the design of antibody drugs broadly and engineer novel CDR-H3 peptide scaffolds as therapeutics