Protonation of Chloro-, Bromo- and Iodo-pentacyanocobaltate(III) Complexes

The reactions between Fe(Phen)₃²⁺[phen = tris-(1,10) phenanthroline] and Co(CN)₅X³⁻ (X = Cl, Br or I) have been studied in aqueous acidic solutions at 25 °C and ionic strength in the range I = 0.001–0.02 mol dm⁻³ (NaCl/HCl). Plots of k₂ versus √I, applying Debye–Huckel Theory, gave the values −1.79 ± 0.18, −1.65 ± 0.18 and 1.81 ± 0.10 as the product of charges (Z_AZ_B) for the reactions of Fe(Phen)₃²⁺ with the chloro-, bromo- and iodo- complexes respectively. Z_AZ_B of ≈ −2 suggests that the charge on these Co^III complexes cannot be −3 but is −1. This suggests the possibility of protonation of these Co^III complexes. Protonation was investigated over the range [H⁺] = 0.0001 −0.06 mol dm⁻³ and the protonation constants K_a obtained are 1.22 × 10³, 7.31 × 10³ and 9.90 × 10² dm⁶ mol⁻³ for X = Cl, Br and I, respectively.     

Liquid chromatographic analysis of vitamin B6 in reconstituted infant formula: collaborative study

A liquid chromatographic (LC) method was validated for the determination of total vitamin B6 in infant formula. Total vitamin B6 was quantified by converting the phosphorylated and free vitamers into pyridoxine. Pyridoxine was determined by ion pair reversed-phase LC with fluorescence detection. The method was subjected to an AOAC collaborative study involving a factory-manufactured, milk- and soy-based infant formula. Each was spiked at 3 concentrations in the range of 0-1 microg/g and sent as blind duplicate to participant laboratories. Nine laboratories returned valid data which were statistically analyzed for outliers and precision parameters. The repeatability relative standard deviation (RSD(r)) ranges were 2.0-4.0 and 3.5-5.9% for fortified milk- and soy-based formulas, respectively. The reproducibility relative standard deviation (RSD(R)) ranges were 8.2-8.4 and 6.7-11.2% for fortified milk- and soy-based formulas, respectively. HORRAT values ranged from 0.42 to 0.53, indicating that the precision of the method is acceptable. The mean RSD(r):RSD(R) values were 0.60 and 0.55 for milk- and soy-based formulas, respectively. As expected, RSDs for the unfortified samples were higher, but their HORRAT values (0.81 and 2.06) helped define a realistic limit of quantitation as 0.05 microg/g. Recovery data were quantitative and varied between 81.4 and 98.0% (mean = 89.8%) for each of 6 spiked materials.     

The synthesis and electronic structure of a novel [NiS4Fe2(CO)6] radical cluster: implications for the active site of the [NiFe] hydrogenases

A novel [NiS4Fe2(CO)6]cluster (1: 'S(4)'=(CH(3)C(6)H(3)S(2))(2)(CH(2))(3)) has been synthesised, structurally characterised and has been shown to undergo a chemically reversible reduction process at -1.31 V versus Fc(+)/Fc to generate the EPR-active monoanion 1(-). Multifrequency Q-, X- and S-band EPR spectra of (61)Ni-enriched 1(-) show a well-resolved quartet hyperfine splitting in the low-field region due to the interaction with a single (61)Ni (I=3/2) nucleus. Simulations of the EPR spectra require the introduction of a single angle of non-coincidence between g(1) and A(1), and g(3) and A(3) to reproduce all of the features in the S- and X-band spectra. This behaviour provides a rare example of the detection and measurement of non-coincidence effects from frozen-solution EPR spectra without the need for single-crystal measurements, and in which the S-band experiment is sensitive to the non-coincidence. An analysis of the EPR spectra of 1(-) reveals a 24 % Ni contribution to the SOMO in 1(-), supporting a delocalisation of the spin-density across the NiFe(2) cluster. This observation is supported by IR spectroscopic results which show that the CO stretching frequencies, nu(CO), shift to lower frequency by about 70 cm(-1) when 1 is reduced to 1(-). Density functional calculations provide a framework for the interpretation of the spectroscopic properties of 1(-) and suggest that the SOMO is delocalised over the whole cluster, but with little S-centre participation. This electronic structure contrasts with that of the Ni-A, -B, -C and -L forms of [NiFe] hydrogenase in which there is considerable S participation in the SOMO.     

Brucine salts of l‐α‐hydr­oxy acids: brucinium hydrogen (S)‐malate penta­hydrate and anhydrous brucinium hydrogen (2R,3R)‐tartrate at 130 K

The structures of two brucinium (2,3‐dimeth­oxy‐10‐oxostrychnidinium) salts of the α‐hydr­oxy acids l ‐malic acid and l ‐tartaric acid, namely brucinium hydrogen (S)‐malate penta­hydrate, C₂₃H₂₇N₂O₄⁺·C₄H₅O₅⁻·5H₂O, (I), and anhydrous brucinium hydrogen (2R,3R)‐tartrate, C₂₃H₂₇N₂O₄⁺·C₄H₅O₆⁻,(II), have been determined at 130 K. Compound (I) has two brucinium cations, two hydrogen malate anions and ten water mol­ecules of solvation in the asymmetric unit, and forms an extensively hydrogen‐bonded three‐dimensional framework structure. In compound (II), the brucinium cations form the common undulating brucine sheet substructures, which accommodate parallel chains of head‐to‐tail hydrogen‐bonded tartrate anion species in the inter­stitial cavities.     

Creation and comparison of MS/MS spectral libraries using quadrupole ion trap and triple-quadrupole mass spectrometers

Searchable libraries of MS/MS spectra, obtained using liquid chromatography/tandem mass spectrometry (LC/MS/MS) with data-dependent scan mode switching on both quadrupole ion trap and triple-quadrupole mass spectrometers in conjunction with electrospray ionization, are presented. The effects on library search scores of changing the parameters for producing collision-induced dissociation (CID) on both instrument types are systematically evaluated. These observations serve as a basis for determining a universal set of conditions for building MS/MS libraries. A group of 19 closely related steroids was used. The ability to obtain library-searchable spectra at low concentrations is demonstrated for the analysis of a sample of progesterone spiked with hydroxyprogesterone impurities at 0.1 and 0.01%.     

The Consensus Problem in Polities of Agents with Dissimilar Cognitive Architectures

Agents interacting with their environments, machine or otherwise, arrive at decisions based on their incomplete access to data and their particular cognitive architecture, including data sampling frequency and memory storage limitations. In particular, the same data streams, sampled and stored differently, may cause agents to arrive at different conclusions and to take different actions. This phenomenon has a drastic impact on polities—populations of agents predicated on the sharing of information. We show that, even under ideal conditions, polities consisting of epistemic agents with heterogeneous cognitive architectures might not achieve consensus concerning what conclusions to draw from datastreams. Transfer entropy applied to a toy model of a polity is analyzed to showcase this effect when the dynamics of the environment is known. As an illustration where the dynamics is not known, we examine empirical data streams relevant to climate and show the consensus problem manifest.     

Nearly invariant subspaces for shift semigroups

Let{T (t)}_t≥0 be a C₀-semigroup on an infinite-dimensional separable Hilbert space; a suitable definition of near{T (t)~*}_t≥0 invariance of a subspace is presented in this paper. A series of prototypical examples for minimal nearly{S(t)~*}t≥0 invariant subspaces for the shift semigroup{S(t)}_t≥0 on L²(0,∞) are demonstrated, which have close links with near T~*_θ invariance on Hardy spaces of the unit disk for an inner function θ. Especially, ...     

The influence of chirality on the behavior of oligonucleotides inside cells: revealing the potent cytotoxicity of G-rich l-RNA

Due to their intrinsic nuclease resistance, mirror image l-oligonucleotides are being increasingly employed in the development of biomedical research tools and therapeutics. Yet, the influence of chirality on the behavior of oligonucleotides in living systems, and specifically, the extent to which l-oligonucleotides interact with endogenous biomacromolecules and the resulting consequences remain unknown. In this study, we characterized the intracellular behavior of l-oligonucleotides for the first time, revealing important chirality-dependent effects on oligonucleotide cytotoxicity. We show that exogenously delivered l-oligonucleotides have the potential to be highly cytotoxic, which is dependent on backbone chemistry, sequence, and structure. Notably, for the sequences tested, we found that single-stranded G-rich l-RNAs are more cytotoxic than their d-DNA/RNA counterparts, exhibiting low nanomolar EC₅₀ values. Importantly, RNA-seq analysis of differentially expressed genes suggests that G-rich l-RNAs stimulate an innate immune response and pro-inflammatory cytokine production. These data not only challenge the general perception that mirror image l-oligonucleotides are nontoxic and nonimmunogenic, but also reveal previously unrecognized therapeutic opportunities. Moreover, by establishing sequence/structure toxicity relationships, this work will guide how future l-oligonucleotide-based biotechnologies are designed and applied.

We determined the influence of chirality on the behavior of oligonucleotides inside human cells, revealing that mirror-image l-oligonucleotides have the potential to be highly cytotoxic.     

MolE8: finding DFT potential energy surface minima values from force-field optimised organic molecules with new machine learning representations

The use of machine learning techniques in computational chemistry has gained significant momentum since large molecular databases are now readily available. Predictions of molecular properties using machine learning have advantages over the traditional quantum mechanics calculations because they can be cheaper computationally without losing the accuracy. We present a new extrapolatable and explainable molecular representation based on bonds, angles and dihedrals that can be used to train machine learning models. The trained models can accurately predict the electronic energy and the free energy of small organic molecules with atom types C, H N and O, with a mean absolute error of 1.2 kcal mol⁻¹. The models can be extrapolated to larger organic molecules with an average error of less than 3.7 kcal mol⁻¹ for 10 or fewer heavy atoms, which represent a chemical space two orders of magnitude larger. The rapid energy predictions of multiple molecules, up to 7 times faster than previous ML models of similar accuracy, has been achieved by sampling geometries around the potential energy surface minima. Therefore, the input geometries do not have to be located precisely on the minima and we show that accurate density functional theory energy predictions can be made from force-field optimised geometries with a mean absolute error 2.5 kcal mol⁻¹.

New representations and machine learning calculate DFT minima from force field geometries.     

Near-Ultraviolet Circular Dichroism and Two-Dimensional Spectroscopy of Polypeptides

A fully quantitative theory of the relationship between protein conformation and optical spectroscopy would facilitate deeper insights into biophysical and simulation studies of protein dynamics and folding. In contrast to intense bands in the far-ultraviolet, near-UV bands are much weaker and have been challenging to compute theoretically. We report some advances in the accuracy of calculations in the near-UV, which were realised through the consideration of the vibrational structure of the electronic transitions of aromatic side chains.