Addressing the safety of new food sources and production systems.

New food sources and production systems (NFPS) are garnering much attention, driven by international trade, changing consumer preferences, potential sustainability benefits, and innovations in climate-resilient food production systems. However, NFPS can introduce new challenges for food safety agencies and food manufacturers. Most food safety hazards linked to new foods have been identified in traditional foods. However, there can be some food safety challenges that are unique to new foods. New food ingredients, inputs, and processes can introduce unexpected contaminants. To realize the full potential of NFPS, there is a need for stakeholders from governments, the food industry, and the research community to collectively work to address and communicate the safety of NFPS products. This review outlines known food safety hazards associated with select NFPS products on the market, namely, plant-derived proteins, seaweeds, jellyfish, insects, microbial proteins, as well as foods derived from cell-based food production, precision fermentation, vertical farming, and 3D food printing. We identify common elements in emerging NFPS regulatory frameworks in various countries/regions. Furthermore, we highlight current efforts in harmonization of terminologies, use of recent scientific tools to fill in food safety knowledge gaps, and international multi-stakeholder collaborations to tackle safety challenges. Although there cannot be a one-size-fits-all approach when it comes to the regulatory oversight for ensuring the safety of NFPS, there is a need to develop consensus-based structured protocols or workflows among stakeholders to facilitate comprehensive, robust, and internationally harmonized approaches. These efforts increase consumers' confidence in the safety of new foods and contribute toward fair practices in the international trade of such foods.

Main Group Molecular Switches with Swivel Bifurcated to Trifurcated Hydrogen Bond Mode of Action.

Artificial molecular machines have captured the full attention of the scientific community since Jean-Pierre Sauvage, Fraser Stoddart, and Ben Feringa were awarded the 2016 Nobel Prize in Chemistry. The past and current developments in molecular machinery (rotaxanes, rotors, and switches) primarily rely on organic-based compounds as molecular building blocks for their assembly and future development. In contrast, the main group chemical space has not been traditionally part of the molecular machine domain. The oxidation states and valency ranges within the p-block provide a tremendous wealth of structures with various chemical properties. Such chemical diversity─when implemented in molecular machines─could become a transformative force in the field. Within this context, we have rationally designed a series of NH-bridged acyclic dimeric cyclodiphosphazane species, [(µ-NH){PE(µ-NtBu)2PE(NHtBu)}2] (E = O and S), bis-PV2N2, displaying bimodal bifurcated R21(8) and trifurcated R31(8,8) hydrogen bonding motifs. The reported species reversibly switch their topological arrangement in the presence and absence of anions. Our results underscore these species as versatile building blocks for molecular machines and switches, as well as supramolecular chemistry and crystal engineering based on cyclophosphazane frameworks.

Beyond the TPP+ "gold standard": a new generation mitochondrial delivery vector based on extended PN frameworks.

Mitochondrial targeting represents an attractive strategy for treating metabolic, degenerative and hyperproliferative diseases, since this organelle plays key roles in essential cellular functions. Triphenylphosphonium (TPP+) moieties - the current "gold standard" - have been widely used as mitochondrial targeting vectors for a wide range of molecular cargo. Recently, further optimisation of the TPP+ platform drew considerable interest as a way to enhance mitochondrial therapies. However, although the modification of this system appears promising, the core structure of the TPP+ moiety remains largely unchanged. Thus, this study explored the use of aminophosphonium (PN+) and phosphazenylphosphonium (PPN+) main group frameworks as novel mitochondrial delivery vectors. The PPN+ moiety was found to be a highly promising platform for this purpose, owing to its unique electronic properties and high lipophilicity. This has been demonstrated by the high mitochondrial accumulation of a PPN+-conjugated fluorophore relative to its TPP+-conjugated counterpart, and has been further supported by density functional theory and molecular dynamics calculations, highlighting the PPN+ moiety's unusual electronic properties. These results demonstrate the potential of novel phosphorus-nitrogen based frameworks as highly effective mitochondrial delivery vectors over traditional TPP+ vectors.

Mechanosynthesis and photophysics of colour-tunable photoluminescent group 13 metal complexes with sterically demanding salen and salophen ligands.

A series of four photoluminescent Al and In complexes were synthesised using an environmentally-benign mechanosynthesis strategy. Sterically crowded 3,5-di-tert-butyl functionalised salophen and salen ligands and their respective complexes have been synthesised in the solid-state and fully characterised. Subsequent photophysics and electrochemistry studies of the resulting complexes suggest that these new group 13 complexes can be viable alternatives to traditional photoluminescent complexes based on expensive and low abundant noble metals. The herein-reported strategy avoids the use of organic solvents and provides a process with low environmental impact and enhanced energy efficiency.

Pre-arranged building block approach for the orthogonal synthesis of an unfolded tetrameric organic-inorganic phosphazane macrocycle.

Inorganic macrocycles remain challenging synthetic targets due to the limited number of strategies reported for their syntheses. Among these species, large fully inorganic cyclodiphosphazane macrocycles have been experimentally and theoretically highlighted as promising candidates for supramolecular chemistry. In contrast, their hybrid organic-inorganic counterparts are lagging behind due to the lack of synthetic routes capable of controlling the size and topological arrangement (i.e., folded vs unfolded) of the target macrocycle, rendering the synthesis of differently sized macrocycles a tedious screening process. Herein, we report-as a proof-of-concept-the combination of pre-arranged building blocks and a two-step synthetic route to rationally enable access a large unfolded tetrameric macrocycle, which is not accessible via conventional synthetic strategies. The obtained macrocycle hybrid cyclodiphosphazane macrocycle, cis-[µ-P(µ-NtBu)]2(µ-p-OC6H4C(O)O)]4[µ-P(µ-NtBu)]2 (4), displays an unfolded open-face cavity area of 110.1 Å2. Preliminary theoretical host-guest studies with the dication [MeNC5H4]22+ suggest compound 4 as a viable candidate for the synthesis of hybrid proto-rotaxanes species based on phosphazane building blocks.

Alkyl vs. aryl modifications: a comparative study on modular modifications of triphenylphosphonium mitochondrial vectors.

Triphenylphosphonium (TPP+) moieties are commonly conjugated to drug molecules to confer mitochondrial selectivity due to their positive charge and high lipophilicity. Although optimisation of lipophilicity can be achieved by modifying the length of the alkyl linkers between the TPP+ moiety and the drug molecule, it is not always possible. While methylation of the TPP+ moiety is a viable alternative to increase lipophilicity and mitochondrial accumulation, there are no studies comparing these two separate modular approaches. Thus, we have systematically designed, synthesised and tested a range of TPP+ molecules with varying alkyl chain lengths and degree of aryl methylation to compare the two modular methodologies for modulating lipophilicity. The ability of aryl/alkyl modified TPP+ to deliver cargo to the mitochondria was also evaluated by confocal imaging with a TPP+-conjugated fluorescein-based fluorophore. Furthermore, we have employed molecular dynamics simulations to understand the translocation of these molecules through biological membrane model systems. These results provide further insights into the thermodynamics of this process and the effect of alkyl and aryl modular modifications.

Size-control in the synthesis of oxo-bridged phosphazane macrocycles via a modular addition approach.

Inorganic macrocycles remain largely underdeveloped compared with their organic counterparts due to the challenges involved in their synthesis. Among them, cyclodiphosphazane macrocycles have shown to be promising candidates for supramolecular chemistry applications due to their ability to encapsulate small molecules or ions within their cavities. However, further developments have been handicapped by the lack of synthetic routes to high-order cyclodiphosphazane macrocycles. Moreover, current approaches allow little control over the size of the macrocycles formed. Here we report the synthesis of high-order oxygen-bridged phosphazane macrocycles via a "3 + n cyclisation" (n = 1 and 3). Using this method, an all-PIII high-order hexameric cyclodiphosphazane macrocycle was isolated, displaying a larger macrocyclic cavity than comparable organic crown-ethers. Our approach demonstrates that increasing building block complexity enables precise control over macrocycle size, which will not only generate future developments in both the phosphazane and main group chemistry but also in the fields of supramolecular chemistry.

N-Bridged Acyclic Trimeric Poly-Cyclodiphosphazanes: Highly Tuneable Cyclodiphosphazane Building Blocks.

We have synthesized a completely new family of acyclic trimeric cyclodiphosphazane compounds comprising NH, Ni Pr, Nt Bu and NPh bridging groups. In addition, the first NH-bridged acyclic dimeric cyclophosphazane has been produced. The trimeric species display highly tuneable characteristics so that the distance between the terminal N(H)R moieties can be readily modulated by the steric bulk present in the bridging groups (ranging from ≈6 to ≈10 Å). Moreover, these species exhibit pronounced topological changes when a weak non-bonding NH⋅⋅⋅π aryl interaction is introduced. Finally, the NH-bridged chloride binding affinities have been calculated and benchmarked along with the existing experimental data available for monomeric cyclodiphosphazanes. Our results underscore these species as promising hydrogen bond donors for supramolecular host-guest applications.

Enabling Mitochondrial Uptake of Lipophilic Dications Using Methylated Triphenylphosphonium Moieties.

Triphenylphosphonium (TPP+) species comprising multiple charges, i.e., bis-TPP+, are predicted to be superior mitochondrial-targeting vectors and are expected to have mitochondrial accumulations 1000-fold greater than TPP+, the current "gold standard". However, bis-TPP+ vectors linked by short hydrocarbon chains ( n < 5) are unable to be taken up by the mitochondria, thus hindering their development as mitochondrial delivery vectors. Through the incorporation of methylated TPP+ moieties (T*PP+), we successfully enabled the accumulation of bis-TPP+ with a short linker chain in isolated mitochondria, as measured by high performance liquid chromatography. These experimental results are further supported by molecular dynamics and ab initio calculations, revealing the strong correlations between mitochondria uptake and molecular volume, surface area, and chemical hardness. Most notably, the molecular volume has been shown to be a strong predictor of accumulation for both mono- and bis-TPP+ salts. Our study underscores the potential of T*PP+ moieties as alternative mitochondrial vectors to overcome low permeation into the mitochondria.