Computational Chemistry to the Rescue: Modern Toolboxes for the Assignment of Complex Molecules by GIAO NMR Calculations

The calculations of NMR properties of molecules using quantum chemical methods have deeply impacted several branches of organic chemistry. They are particularly important in structural or stereochemical assignments of organic compounds, with implications in total synthesis, stereoselective reactions, and natural products chemistry. In studying the evolution of the strategies developed to support (or reject) a structural proposal, it becomes clear that the most effective and accurate ones involve sophisticated procedures to correlate experimental and computational data. Owing to their relatively high mathematical complexity, such calculations (CP3, DP4, ANN‐PRA) are often carried out using additional computational resources provided by the authors (such as applets or Excel files). This Minireview will cover the state‐of‐the‐art of these toolboxes in the assignment of organic molecules, including mathematical definitions, updates, and discussion of relevant examples.     

Two new polyketides from Hawaiian endophytic fungus Pestalotiopsis sp. FT172

Two new polyketides, pestalotiotones A (1) and B (2) were isolated from the cultured broth of Pestalotiopsis sp. FT172. The structures of compounds 1 and 2 were determined by analysis of HRMS and NMR spectroscopic data. The absolute configurations of compound 1 were assigned by Mosher reaction, J-based configuration analysis, and DP4 NMR calculations. Both compounds were tested against cancer cell lines, pathogenic fungi and bacteria.     

Effect of the ribose versus 2'-deoxyribose residue on the metal ion-binding properties of purine nucleotides

The interaction between metal ions and nucleotides is well characterized, as is their importance for metabolic processes, e.g. in the synthesis of nucleic acids. Hence, it is surprising to find that no detailed comparison is available of the metal ion-binding properties between nucleoside 5'-phosphates and 2'-deoxynucleoside 5'-phosphates. Therefore, we have measured here by potentiometric pH titrations the stabilities of several metal ion complexes formed with 2'-deoxyadenosine 5'-monophosphate (dAMP2-), 2'-deoxyadenosine 5'-diphosphate (dADP3-) and 2'-deoxyadenosine 5'-triphosphate (dATP4-). These results are compared with previous data measured under the same conditions and available in the literature for the adenosine 5'-phosphates, AMP(2-), ADP(3-) and ATP(4-), as well as guanosine 5'-monophosphate (GMP(2-)) and 2'-deoxyguanosine 5'-monophosphate (dGMP(2-)). Hence, in total four nucleotide pairs, GMP(2-)/dGMP(2-), AMP(2-)/dAMP(2-), ADP(3-)/dADP(3-) and ATP(4-)/dATP(4-) (= NP/dNP), could be compared for the four metal ions Mg2+, Ni2+, Cu2+ and Zn2+ (= M2+). The comparisons show that complex stability and extent of macrochelate formation between the phosphate-coordinated metal ion and N7 of the purine residue is very similar (or even identical) for the AMP(2-)/dAMP(2-) and ADP(3-)/dADP(3-) pairs. In the case of the complexes formed with ATP(4-)/dATP(4-) the 2'-deoxy complexes are somewhat more stable and show also a slightly enhanced tendency for macrochelate formation. This is different for guanine nucleotides: the stabilities of the M(dGMP) complexes are clearly higher, as are the formation degrees of their macrochelates, than is the case with the M(GMP) complexes. This enhanced complex stability and greater tendency to form macrochelates can be attributed to the enhanced basicity (DeltapKaca. 0.2) of N7 in the 2'-deoxy compound. These results allow general conclusions regarding nucleic acids to be made.     

Solvation phenomena in dilute multicomponent solutions I. Formal results and molecular outlook

We derive second-order thermodynamically consistent truncated composition expansions for the species residual partial molar properties--including volume, enthalpy, entropy, and Gibbs free energy--of dilute ternary systems aimed at the molecular account of solvation phenomena in compressible media. Then, we provide explicit microscopic interpretation of the expansion coefficients in terms of direct and total correlation function integrals over the microstructure of the corresponding infinite dilution reference system, as well as their pressure and temperature derivatives, allowing for the direct prediction of the species partial molar properties from the knowledge of the effective intermolecular interactions. Finally, we apply these formal results (a) to derive consistent expressions for the corresponding properties of the binary system counterparts, (b) to illustrate how the formal expressions converge, at the zero density limit, to those for multicomponent mixtures of imperfect gases obeying the virial equation of state Z = 1 + BPkT, and (c) to discuss, and highlight with examples from the literature, the thermodynamic inconsistencies encountered in the currently available first-order truncated expansions, by pinpointing the mathematical origin and physical meaning of the inconsistencies that render the first-order truncated expansions invalid.     

Harmonic functions of linear growth on solvable groups

We answer a question posed by Bonilla and Grosse-Erdmann by showing that the operators P(D) on the space of entire functions H(C), where D is the differentiation operator and P is a polynomial, do not possess a frequently hypercyclic subspace.     

A new ruthenium nitrosyl species based on a pendant-arm 1,4,8,11-tetraazacyclotetradecane (cyclam) derivative: An experimental and theoretical study

The complex cis-[Ru(L^py)NO]³⁺ (I) (L^py = N-(2-methylpyridyl)1,4,8,11-tetraazacyclotetradecane) was prepared by the stoichiometric reaction between Ru(dmso)₄Cl₂ and L^py and an excess of NaNO₂ in ethanolic medium, followed by acidification of the solution. The diamagnetic species was isolated as its hexafluorophosphate salt, and fully characterized by IR (ν_NO = 1917 cm⁻¹) and diverse NMR techniques in combination with theoretical computations based on the density functional theory (DFT). The compound displays strong electronic transitions below 300 nm and weak ones in the visible region of the spectrum, all of them solvent insensitive. The reaction of cis-[Ru(L^py)NO]³⁺ with OH⁻ generates the strongly colored nitro compound cis-[Ru(L^py)NO₂]⁺ (II) The {RuNO}⁶ compound can be interconverted into the one-electron reduced {RuNO}⁷ species cis-[Ru(L^py)NO]²⁺ (III). The reduction process is completely reversible in the cyclic voltammetry timescale with E⁰ (versus Ag/AgCl, 3 M Cl⁻) = −0.02 V and 0.18 V in water and acetonitrile, respectively. Controlled potential reduction in both solvents yields to the quantitative formation of III, a process which involves significant changes in the electronic spectroscopy. The {RuNO}⁷ species proved to be inert against ligand loss, and electrogenerated solutions remained unchanged for several hours if protected from atmospheric oxygen. Electrochemical reoxidation or exposure to air lead to the complete recovery of the starting cis-[Ru(L^py)NO]³⁺ material, without signs of secondary reactions. The robustness of the coordination sphere appears as a consequence of the multidentate nature of L^py.     

Entropic Dynamics: Quantum Mechanics from Entropy and Information Geometry

Entropic Dynamics (ED) is a framework in which Quantum Mechanics (QM) is derived as an application of entropic methods of inference. The magnitude of the wave function is manifestly epistemic: its square is a probability distribution. The epistemic nature of the phase of the wave function is also clear: it controls the flow of probability. The dynamics is driven by entropy subject to constraints that capture the relevant physical information. The central concern is to identify those constraints and how they are updated. After reviewing previous work I describe how considerations from information geometry allow us to derive a phase space geometry that combines Riemannian, symplectic, and complex structures. The ED that preserves these structures is QM. The full equivalence between ED and QM is achieved by taking account of how gauge symmetry and charge quantization are intimately related to quantum phases and the single‐valuedness of wave functions.     

Determination of polybrominated diphenyl ethers in water and soil samples by cloud point extraction-ultrasound-assisted back-extraction-gas chromatography–mass spectrometry

A novel and efficient analytical methodology is proposed for extracting and preconcentrating polybrominated diphenyl ethers (PBDEs) from samples of environmental interest prior gas chromatography–mass spectrometry (GC–MS) analysis. It is based on the induction of micellar organized medium by using a non-ionic surfactant (Triton X-114) to extract the target PBDEs. To enable coupling the efficient extracting technique with GC analysis, ultrasound-assisted back-extraction (UABE) into an organic solvent was required. Several factors, including surfactant type and concentration, equilibration temperature and time, ionic strength, pH and buffers nature and concentration were studied and optimized over the extraction efficiency of the proposed technique. Under optimal experimental conditions, the target analytes were quantitatively extracted achieving an enrichment factor of 250 when 10 mL aliquot of ultrapure water spiked with PBDE-standard mixture (10 pg mL⁻¹ each PBDE) was extracted. Method detection limits (MDLs) calculated with aqueous PBDEs solutions as three times the signal-to-noise ratio (S/N), ranged from 1 to 2 pg mL⁻¹ with RSDs values ≤8.5% (n = 5). The coefficients of estimation of the calibration curves obtained following the proposed methodology were ≥0.9987 and linear range of all PBDEs was 4–150 pg mL⁻¹. The proposed methodology was validated by carrying out a recovery study by spiking the samples at two different concentration levels of PBDEs (10 and 50 pg mL⁻¹ for waters samples). Recoveries values in the range of 96–106% for water samples were obtained showing satisfactory robustness of the method for analyzing PBDEs in water samples. The proposed methodology was applied for the analysis of PBDEs: 2,2′,4,4′-tetraBDE (BDE-47), 2,2′,4,4,5-pentaBDE (BDE-99), 2,2′,4,4,6-pentaBDE (BDE-100) and 2,2,4,4′,5,5′-hexaBDE (BDE-153) in water samples, including drinking, lake, river water and soil samples. Significant quantities of PBDEs were not found in the analyzed samples.     

A mathematical model for the first-pass dynamics of antibiotics acting on the cardiovascular system

We present a preliminary first-pass dynamic model for delivery of drug compounds to the lungs and heart. We use a compartmental mass-balance approach to develop a system of nonlinear differential equations for mass accumulated in the heart as a result of intravenous injection. We discuss sensitivity analysis as well as methodology for minimizing mass in the heart while maximizing mass delivered to the lungs on a first circulatory pass.     

Properties that Four-Dimensional Objects Cannot Have

The paper argues that four-dimensionalism is incompatible with the existence of “additively cumulative” properties, including mass, volume, and electrical charge. These properties add up over disjoint objects: for example, the mass of a whole composed of two disjoint objects is a sum of the individual masses of the objects. The difficulty with such properties for four-dimensionalism stems from the way this theory makes persistence depend on the existence of disjoint objects at disjoint times. I consider various possible responses to this difficulty and conclude that they all fail.