Enhanced selectivity for acidic contaminants in drinking water: From suspect screening to toxicity prediction.

A novel analytical workflow for suspect screening of organic acidic contaminants in drinking water is presented, featuring selective extraction by silica-based strong anion-exchange solid-phase extraction, mixed-mode liquid chromatography-high resolution accurate mass spectrometry (LC-HRMS), peak detection, feature reduction and compound identification. The novel use of an ammonium bicarbonate-based elution solvent extended strong anion-exchange solid-phase extraction applicability to LC-HRMS of strong acids. This approach performed with consistently higher recovery and repeatability (88 ± 7 % at 500 ng L-1), improved selectivity and lower matrix interference (mean = 12 %) over a generic mixed-mode weak anion exchange SPE method. In addition, a novel filter for reducing full-scan features from fulvic and humic acids was successfully introduced, reducing workload and potential for false positives. The workflow was then applied to 10 London municipal drinking water samples, revealing the presence of 22 confirmed and 37 tentatively identified substances. Several poorly investigated and potentially harmful compounds were found which included halogenated hydroxy-cyclopentene-diones and dibromomethanesulfonic acid. Some of these compounds have been reported as mutagenic in test systems and thus their presence here requires further investigation. Overall, this approach demonstrated that employing selective extraction improved detection and helped shortlist suspects and potentially toxic chemical contaminants with higher confidence.

Hand-portable HPLC with broadband spectral detection enables analysis of complex polycyclic aromatic hydrocarbon mixtures.

Polycyclic aromatic hydrocarbons (PAHs) are considered priority hazardous substances due to their carcinogenic activity and risk to public health. Strict regulations are in place limiting their release into the environment, but enforcement is hampered by a lack of adequate field-testing procedure, instead relying on sending samples to centralised analytical facilities. Reliably monitoring levels of PAHs in the field is a challenge, owing to the lack of field-deployable analytical methods able to separate, identify, and quantify the complex mixtures in which PAHs are typically observed. Here, we report the development of a hand-portable system based on high-performance liquid chromatography incorporating a spectrally wide absorption detector, capable of fingerprinting PAHs based on their characteristic spectral absorption profiles: identifying 100% of the 24 PAHs tested, including full coverage of the United States Environmental Protection Agency priority pollutant list. We report unsupervised methods to exploit these new capabilities for feature detection and identification, robust enough to detect and classify co-eluting and hidden peaks. Identification is fully independent of their characteristic retention times, mitigating matrix effects which can preclude reliable determination of these analytes in challenging samples. We anticipate the platform to enable more sophisticated analytical measurements, supporting real-time decision making in the field.

Environmental control programs the emergence of distinct functional ensembles from unconstrained chemical reactions.

Many approaches to the origin of life focus on how the molecules found in biology might be made in the absence of biological processes, from the simplest plausible starting materials. Another approach could be to view the emergence of the chemistry of biology as process whereby the environment effectively directs "primordial soups" toward structure, function, and genetic systems over time. This does not require the molecules found in biology today to be made initially, and leads to the hypothesis that environment can direct chemical soups toward order, and eventually living systems. Herein, we show how unconstrained condensation reactions can be steered by changes in the reaction environment, such as order of reactant addition, and addition of salts or minerals. Using omics techniques to survey the resulting chemical ensembles we demonstrate there are distinct, significant, and reproducible differences between the product mixtures. Furthermore, we observe that these differences in composition have consequences, manifested in clearly different structural and functional properties. We demonstrate that simple variations in environmental parameters lead to differentiation of distinct chemical ensembles from both amino acid mixtures and a primordial soup model. We show that the synthetic complexity emerging from such unconstrained reactions is not as intractable as often suggested, when viewed through a chemically agnostic lens. An open approach to complexity can generate compositional, structural, and functional diversity from fixed sets of simple starting materials, suggesting that differentiation of chemical ensembles can occur in the wider environment without the need for biological machinery.

Stereoselective Assembly of Gigantic Chiral Molybdenum Blue Wheels Using Lanthanide Ions and Amino Acids.

The synthesis of chiral polyoxometalates (POMs) is a challenge because of the difficulty to induce the formation of intrinsically chiral metal-oxo frameworks. Herein we report the stereoselective synthesis of a series of gigantic chiral Mo Blue (MB) POM clusters 1-5 that are formed by exploiting the synergy between coordinating lanthanides ions as symmetry breakers to produce MBs with chiral frameworks decorated with amino acids ligands; these promote the selective formation of enantiopure MBs. All the compounds share the same framework archetype, based on {Mo124Ce4}, which forms an intrinsically chiral Δ or Λ configurations, controlled by the configurations of functionalized chiral amino acids. The chirality and stability of 1-5 in solution are confirmed by circular dichroism, 1H NMR, and electrospray ion mobility-mass spectrometry studies. In addition, the framework of the {Mo124Ce4} MB not only behaves as a host able to trap a chiral {Mo8} cluster that is not accessible by traditional synthesis but also promotes the transformation of tryptophan to kynurenine in situ. This work demonstrates the potential and applicability of our synthetic strategy to produce gigantic chiral POM clusters capable of host-guest chemistry and selective synthetic transformations.

Miller-Urey Spark-Discharge Experiments in the Deuterium World.

We designed and conducted a series of primordial-soup Miller-Urey style experiments with deuterated gases and reagents to compare the spark-discharge products of a "deuterated world" with the standard reaction in the "hydrogenated world". While the deuteration of the system has little effect on the distribution of amino acid products, significant differences are seen in other regions of the product-space. Not only do we observe about 120 new species, we also see significant differences in their distribution if the two hydrogen isotope worlds are compared. Several isotopologue matches can be identified in both, but a large proportion of products have no equivalent in the corresponding isotope world with ca. 43 new species in the D world and ca. 39 new species in the H world. This shows that isotopic exchange (the addition of only one neutron) may lead to significant additional complexity in chemical space under otherwise identical reaction conditions.

Spontaneous Assembly of an Organic-Inorganic Nucleic Acid Z-DNA Double-Helix Structure.

Herein, we report a hybrid polyoxometalate organic-inorganic compound, Na2 [(HGMP)2 Mo5 O15 ]⋅7 H2 O (1; where GMP=guanosine monophosphate), which spontaneously assembles into a structure with dimensions that are strikingly similar to those of the naturally occurring left-handed Z-form of DNA. The helical parameters in the crystal structure of the new compound, such as rise per turn and helical twist per dimer, are nearly identical to this DNA conformation, allowing a close comparison of the two structures. Solution circular dichroism studies show that compound 1 also forms extended secondary structures in solution. Gel electrophoresis studies demonstrate the formation of non-covalent adducts with natural plasmids. Thus we show a route by which simple hybrid inorganic-organic monomers, such as compound 1, can spontaneously assemble into a double helix without the need for a covalently connected linear sequence of nucleic acid base pairs.

Overcoming the Crystallization Bottleneck: A Family of Gigantic Inorganic {Pdx }(L) (x=84, 72) Palladium Macrocycles Discovered using Solution Techniques.

The {Pd84 }(Ac) wheel, initially discovered serendipitously, is the only reported giant palladium macrocycle-a unique structure that spontaneously assembles from small building blocks. Analogues of this structure are elusive. A new modular route to {Pd84 }(Ac) is described, allowing incorporation of other ligands, and a new screening approach to cluster discovery. Structural assignments were made of new species from solution experiments, overcoming the need for crystallographic analysis. As a result, two new palladium macrocycles were discovered: a structural analogue of the existing {Pd84 }(Ac) wheel with glycolate ligands, {Pd84 }(Gly) , and the next in a magic number series for this cluster family-a new {Pd72 }(Prop) wheel decorated with propionate ligands. These findings confirm predictions of a magic number rule for the family of {Pdx } macrocycles. Furthermore, structures with variable fractions of functional ligands were obtained. Together these discoveries establish palladium clusters as a new class of tunable nanostructures. In facilitating the discovery of species that would not have been discovered by orthodox crystallization approaches, this work also demonstrates the value of solution-based screening and characterization in cluster chemistry, as a means to decouple cluster formation, discovery, and isolation.

Self-Templating and In†Situ Assembly of a Cubic Cluster-of-Clusters Architecture Based on a {Mo24 Fe12 } Inorganic Macrocycle.

Engineering self-templating inorganic architectures is critical for the development of bottom-up approaches to nanoscience, but systems with a hierarchy of templates are elusive. Herein we describe that the cluster-anion-templated (CAT) assembly of a {CAT}⊂{Mo24 Fe12 } macrocycle forms a giant ca. 220 nm(3) unit cell containing 16 macrocycles clustered into eight face-shared tetrahedral cluster-of-clusters assemblies. We show that {CAT}⊂{Mo24 Fe12 } with different CATs gives the compounds 1-4 for CAT=Anderson {FeMo6 } (1), Keggin {PMo12 } (2), Dawson {P2 W18 } (3), and {Mo12 O36 (HPO3 )2 } (4) polyoxometalates. "Template-free" assembly can be achieved, whereby the macrocycle components can also form a template in situ allowing template to macrocycle to superstructure formation and the ability to exchange the templates. Furthermore, the transformation of template clusters within the inorganic macrocycle {Mo24 Fe12 } allows the self-generation of an uncapped {Mo12 O36 (HPO3 )2 } in compound 4.

Sizing and Discovery of Nanosized Polyoxometalate Clusters by Mass Spectrometry.

Ion mobility-mass spectrometry (IM-MS) is a powerful technique for structural characterization, e.g., sizing and conformation, particularly when combined with quantitative modeling and comparison to theoretical values. Traveling wave IM-MS (TW-IM-MS) has recently become commercially available to nonspecialist groups and has been exploited in the structural study of large biomolecules, however reliable calibrants for large anions have not been available. Polyoxometalate (POM) species-nanoscale inorganic anions-share many of the facets of large biomolecules, however, the full potential of IM-MS in their study has yet to be realized due to a lack of suitable calibration data or validated theoretical models. Herein we address these limitations by reporting DT-IM (drift tube) data for a set of POM clusters {M12} Keggin 1, {M18} Dawson 2, and two {M7} Anderson derivatives 3 and 4 which demonstrate their use as a TW-IM-MS calibrant set to facilitate characterization of very large (ca. 1-4 nm) anionic species. The data was also used to assess the validity of standard techniques to model the collision cross sections of large inorganic anions using the nanoscale family of compounds based upon the {Se2W29} unit including the trimer, {Se8W86O299} A, tetramer, {Se8W116O408} B, and hexamer {Se12W174O612} C, including their relative sizing in solution. Furthermore, using this data set, we demonstrated how IM-MS can be used to conveniently characterize and identify the synthesis of two new, i.e., previously unreported POM species, {P8W116}, unknown D, and {Te8W116}, unknown E, which are not amenable to analysis by other means with the approximate formulation of [H34W118X8M2O416](44-), where X = P and M = Co for D and X = Te and M = Mn for E. This work establishes a new type of inorganic calibrant for IM-MS allowing sizing, structural analysis, and discovery of molecular nanostructures directly from solution.

Formation of oligopeptides in high yield under simple programmable conditions.

Many high-yielding reactions for forming peptide bonds have been developed but these are complex, requiring activated amino-acid precursors and heterogeneous supports. Herein we demonstrate the programmable one-pot dehydration-hydration condensation of amino acids forming oligopeptide chains in around 50% yield. A digital recursive reactor system was developed to investigate this process, performing these reactions with control over parameters such as temperature, number of cycles, cycle duration, initial monomer concentration and initial pH. Glycine oligopeptides up to 20 amino acids long were formed with very high monomer-to-oligomer conversion, and the majority of these products comprised three amino acid residues or more. Having established the formation of glycine homo-oligopeptides, we then demonstrated the co-condensation of glycine with eight other amino acids (Ala, Asp, Glu, His, Lys, Pro, Thr and Val), incorporating a range of side-chain functionality.

Configurable Nanosized Metal Oxide Oligomers via Precise "Click" Coupling Control of Hybrid Polyoxometalates.

Polyoxometalates (POMs) are discrete clusters of redox-active metal oxides, many of which can be linked to organic moieties. Here, we show how it is possible to link Mn Anderson POMs to terminal alkyne and azide groups and develop appropriate conditions for their Cu-catalyzed alkyne-azide cycloaddition (or "click" reaction). These coupling reactions are then used to link the clusters together, forming monodisperse linear Mn Anderson oligomers, here with examples ranging in size from two to five clusters. These oligomers are built up sequentially using a combination of mono- and difunctionalized clusters, giving an unprecedented level of control over the size and structure of the resulting hybrid POMs. This new synthetic methodology therefore opens the way for the synthesis of metal oxide hybrid oligomers and polymers by coupling control, minimizing side products, producing nanosized molecular hybrid organic-inorganic oxides ca. 4-9 nm in size, with molecular weights ranging 2-10 kDa.

Controlling the ring curvature, solution assembly, and reactivity of gigantic molybdenum blue wheels.

We describe the synthesis, structure, self-assembly, solution chemistry, and mass spectrometry of two new gigantic decameric molybdenum blue wheels, {Mo200Ce12} (1) and {Mo100Ce6} (2), by building block rearrangement of the tetradecameric {Mo154} framework archetype and control of the architecture's curvature in solution from the addition of Ce(III). The assembly of 1 and 2 could be directed accordingly by adjusting the ionic strength and acidity of the reaction mixture. Alternatively, the dimeric cluster {Mo200Ce12} could be transformed directly to the monomeric species {Mo100Ce6} upon addition of a potassium salt. ESI-ion mobility mass spectra were successfully obtained for both {Mo200Ce12} and {Mo100Ce6}, which is the first report in molybdenum blue chemistry thereby confirming that the gigantic clusters are stable in solution and that ion mobility measurements can be used to characterize nanoscale inorganic molecules.

Exploring the symmetry, structure, and self-assembly mechanism of a gigantic seven-fold symmetric {Pd84} wheel.

The symmetry, structure and formation mechanism of the structurally self-complementary {Pd84} = [Pd84O42(PO4)42(CH3CO2)28](70-) wheel is explored. Not only does the symmetry give rise to a non-closest packed structure, the mechanism of the wheel formation is proposed to depend on the delicate balance between reaction conditions. We achieve the resolution of gigantic polyoxopalladate species through electrophoresis and size-exclusion chromatography, the latter has been used in conjunction with electrospray mass spectrometry to probe the formation of the ring, which was found to proceed by the stepwise aggregation of {Pd6}(-) = [Pd6O4(CH3CO2)2(PO4)3Na(6-n)H(n)](-) building blocks. Furthermore, the higher-order assembly of these clusters into hollow blackberry structures of around 50 nm has been observed using dynamic and static light scattering.

Polyoxometalate clusters integrated into peptide chains and as inorganic amino acids: solution- and solid-phase approaches.

General synthetic methods for the grafting of peptide chains onto polyoxometalate clusters by the use of general activated precursors have been developed. Using a solution-phase approach, pre-synthesized peptides can be grafted to a metal oxide cluster to produce hybrids of unprecedented scale (up to 30 residues). An adapted solid-phase method allows the incorporation of these clusters, which may be regarded as novel hybrid unnatural amino acids, during the peptide synthesis itself. These methods may open the way for the automated synthesis of peptides and perhaps even proteins that contain "inorganic" amino acids.

Use of ion-mobility mass spectrometry (IMS-MS) to map polyoxometalate Keplerate clusters and their supramolecular assemblies.

We present the high-resolution (HRES-MS) and ion-mobility (IMS-MS) mass spectrometry studies of icosahedral nanoscale polyoxometalate-based {L(30)}{(Mo)Mo(5)} Keplerate clusters, and demonstrate the use of IMS-MS to resolve and map intact nanoclusters, and its potential for the discovery of new structures, in this case the first gas phase observation of 'proto-clustering' of higher order Keplerate supramolecular aggregates.

A pyrophosphate-responsive gadolinium(III) MRI contrast agent.

This study shows that the relaxivity and optical properties of functionalised lanthanide-DTPA-bis-amide complexes (lanthanide=Gd(3+) and Eu(3+) , DTPA=diethylene triamine pentaacetic acid) can be successfully modulated by addition of specific anions, without direct Ln(3+) /anion coordination. Zinc(II)-dipicolylamine moieties, which are known to bind strongly to phosphates, were introduced in the amide "arms" of these ligands, and the interaction of the resulting Gd-Zn(2) complexes with a range of anions was screened by using indicator displacement assays (IDAs). Considerable selectivity for polyphosphorylated species (such as pyrophosphate and adenosine-5'-triphosphate (ATP)) over a range of other anions (including monophosphorylated anions) was apparent. In addition, we show that pyrophosphate modulates the relaxivity of the gadolinium(III) complex, this modulation being sufficiently large to be observed in imaging experiments. To establish the binding mode of the pyrophosphate and gain insight into the origin of the relaxometric modulation, a series of studies including UV/Vis and emission spectroscopy, luminescence lifetime measurements in H(2) O and D(2) O, (17) O and (31) P NMR spectroscopy and nuclear magnetic resonance dispersion (NMRD) studies were carried out.