Studies of Hindered Rotation and Magnetic Anisotropy by 1H, 13C and 19F NMR. The Diels-Alder Adduct of N- Pentafluorophenylmaleimide and Phencyclone: A Model for Drugs.

The potent Diels-Alder diene, phencyclone, 1, reacts with N-pentafluorophenylmaleimide, 2, to form an adduct, 3, characterized by ¹H, ¹³C, and ¹⁹F NMR at 300, 75 and 282 MHz, respectively. The one-dimensional (1D) and two-dimensional (2D) ¹H and ¹³C NMR spectra of 3 at ambient temperatures imply a slow exchange limit (SEL) regime with respect to rotation of the unsubstituted bridgehead phenyl groups about severely hindered C(sp²)-C(sp³) bonds. Major non-bonded interactions are expected between the ortho protons of the C₆H₅ groups and H-1, 8 of the phenanthrenoid moiety of 3. ¹⁹F 1D and 2D (COSY) NMR spectra show that the SEL regime also obtains for rotation about the N-C₆F₅ bond of 3, with five separate fluorine signals seen, consistent with a preferred conformation in which the C₆F₅ may lie roughly perpendicular to the plane of the pyrrolidinedione moiety, and may be in the mirror symmetry plane of 3. The results are considered relevant to hindered aryl rotations in numerous Pharmaceuticals. Selected spectral data for 2 and precursors are also presented.     

Frequency modules and nonexistence of quasi-periodic solutions of nonlinear evolution equations

This paper gives lower estimates for the frequency modules of almost periodic solutions to equations of the form , where A generates a strongly continuous semigroup in a Banach space , F(t,x) is 2π-periodic in t and continuous in (t,x), and f is almost periodic. We show that the frequency module ℳ(u) of any almost periodic mild solution u of (*) and the frequency module ℳ(f) of f satisfy the estimate e ^{2π iℳ(f)}⊂e ^{2π iℳ(u)}. If F is independent of t, then the estimate can be improved: ℳ(f)⊂ℳ(u). Applications to the nonexistence of quasi-periodic solutions are also given.     

On the Kolmogorov complexity of continuous real functions

Kolmogorov complexity was originally defined for finitely-representable objects. Later, the definition was extended to real numbers based on the asymptotic behaviour of the sequence of the Kolmogorov complexities of the finitely-representable objects—such as rational numbers—used to approximate them.This idea will be taken further here by extending the definition to continuous functions over real numbers, based on the fact that every continuous real function can be represented as the limit of a sequence of finitely-representable enclosures, such as polynomials with rational coefficients.Based on this definition, we will prove that for any growth rate imaginable, there are real functions whose Kolmogorov complexities have higher growth rates. In fact, using the concept of prevalence, we will prove that ‘almost every’ continuous real function has such a high-growth Kolmogorov complexity. An asymptotic bound on the Kolmogorov complexities of total single-valued computable real functions will be presented as well.     

Optical and current transport properties of CuO/ZnO nanocoral p–n heterostructure hydrothermally synthesized at low temperature

We demonstrate the synthesis and investigate the electrical and optical characteristics of ‘nanocorals’ (NCs) composed of CuO/ZnO grown at low temperature through the hydrothermal approach. High-density CuO nanostructures (NSs) were selectively grown on ZnO nanorods (NRs). The synthesized NCs were used to fabricate p–n heterojunctions that were investigated by the current density–voltage (J–V) and the capacitance–voltage (C–V) techniques. It was found that the NC heterojunctions exhibit a well-defined diode behavior with a threshold voltage of about 1.52 V and relatively high rectification factor of ～760. The detailed forward J–V characteristics revealed that the current transport is controlled by an ohmic behavior for V≤0.15 V, whereas at moderate voltages 1.46≤V<1.5 the current follows a J? α?exp(βV) relationship. At higher voltages (≥1.5 V) the current follows the relation J? α? V ², indicating that the space-charge-limited current mechanism is the dominant current transport. The C–V measurement indicated that the NC diode has an abrupt junction. The grown CuO/ZnO NCs exhibited a broad light absorption range that is covering the UV and the entire visible parts of the spectrum.     

Recent Advances in the Chemistry and Therapeutic Evaluation of Naturally Occurring and Synthetic Withanolides

Natural products are a major source of biologically active compounds that make promising lead molecules for developing efficacious drug-like molecules. Natural withanolides are found in many flora and fauna, including plants, algae, and corals, that traditionally have shown multiple health benefits and are known for their anti-cancer, anti-inflammatory, anti-bacterial, anti-leishmaniasis, and many other medicinal properties. Structures of these withanolides possess a few reactive sites that can be exploited to design and synthesize more potent and safe analogs. In this review, we discuss the literature evidence related to the medicinal implications, particularly anticancer properties of natural withanolides and their synthetic analogs, and provide perspectives on the translational potential of these promising compounds.     

Gut microbiota, diet, and heart disease

Modulation of the gut microbiota is an area of growing interest, particularly for its link to improving and maintaining the systemic health of the host. It has been suggested to have potential to reduce risk factors associated with chronic diseases, such as elevated cholesterol levels in coronary heart disease (CHD). Diets of our evolutionary ancestors were largely based on plant foods, high in dietary fiber and fermentable substrate, and our gut microbiota has evolved against a background of such diets. Therapeutic diets that mimic plant-based diets from the early phases of human evolution may result in drug-like cholesterol reductions. In contrast, typical Western diets low in dietary fiber and fermentable substrate, and high in saturated and trans fatty acids, are likely contributors to the increased need for pharmacological agents for cholesterol reduction. The gut microbiota of those consuming a Western diet are likely underutilized and depleted of metabolic fuels, resulting in a less than optimal gut microbial profile. As a result, this diet is mismatched to our archaic gut microbiota and, therefore, to our genome, which has changed relatively little since humans first appeared. While the exact mechanism by which the gut microbiota may modulate cholesterol levels still remains uncertain, end products of bacterial fermentation, particularly the short chain fatty acids (i.e., propionate), have been suggested as potential candidates. While more research is required to clarify the potential link between gut microbiota and CHD risk reduction, consuming a therapeutic diet rich in plant foods, dietary fiber, and fermentable substrate would be a useful strategy for improving systemic health, possibly by altering the gut microbiota.     

Urease inhibition and anti-leishmanial assay of substituted benzoylguanidines and their copper(II) complexes

A series of N,N',N'-trisubstituted guanidines (1-6) and their copper(II) complexes, [κ(2)(O,N)-C(6)H(5)CONHC(NHC(6)H(4)Cl)NR](2)Cu(ii) (R = iso-propyl (1a), n-butyl (2a), sec-butyl (3a), tert-butyl (4a), benzyl (5a), and para-tolyl (6a)) were synthesized and characterized using elemental analysis, FTIR and NMR spectroscopy. DFT studies were used to assess the location of the protons in the free ligands. However, calculations have shown that, in all cases, hydrogen bonding from either N-H group gives conformations that are very similar in energy. Single crystal XRD studies were used to characterize ligands 1 and 4 and the related complexes 1a and 4a. The structures reveal that these complexes are mononuclear in the solid state and that copper adopts a regular square planar geometry. In both metallic species, the N, N', N'-trisubstituted guanidine ligands chelate the Cu(II) atom using the oxygen and one nitrogen. The synthesized compounds were investigated for urease inhibition using thiourea as a standard drug. Most complexes exhibit a better activity than the respective guanidines and compound 1a was found to be the most active with IC(50) = 9.83 ± 0.07 μM (the IC(50) for thiourea is 21.0 ± 0.1 μM). The species were also screened for their anti-leishmanial activity. However, all of the compounds were devoid of any significant activity.     

Borate binding to siderophores: structure and stability

Well-known as specific iron chelating agents produced by bacteria, it is shown that some, but not all, siderophore classes have an unexpected binding affinity for boron. The relevant criterium is the availability of a vicinal dianionic oxygen containing binding group (i.e., citrate or catecholate). The resulting boron complexes have been characterized by ESI-MS, multinuclear NMR, and DFT calculations. Detailed boron binding constants have been measured for vibrioferrin, rhizoferrin, and petrobactin. The observed affinity of certain siderophores for borate, a common chemical species in the marine but not the terrestrial environment, allows for small, but potentially significant, concentrations of B-siderophores to exist at oceanic pH. We hypothesize that these concentrations could be sufficient for them to function as cell signaling molecules or as mediators of biological boron uptake. In addition, binding of the tetrahedral boron to these siderophores results in a conformation that is different from either the free siderophore or its iron complex and would thus allow a distinction to be made between its iron uptake and any putative cell signaling roles.