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Human serum albumin (HSA) efficiently transports drugs in vivo: most are organic. Therefore, it is important to delineate the binding of small molecules to HSA. Here, for the first time, we show that HSA binding depends not only on the identity of the d8 metal ion, NiII or PdII, of their complexes with bis(pyrrole-imine), H2PrPyrr, but on the pH level as well. Fluorescence quenching data for native and probe-bound HSA showed that sites close to Trp-214 (subdomain IIA) are targeted. The affinity constants, Ka, ranged from ~3.5 × 103 M-1 to ~1 × 106 M-1 at 37 °C, following the order Pd(PrPyrr) > Ni(PrPyrr) at pH levels of 4 and 7; but Ni(PrPyrr) > Pd(PrPyrr) at a pH level of 9. Ligand uptake is enthalpically driven, dependent mainly on London dispersion forces. The induced CD spectra for the protein-bound ligands could be simulated by hybrid QM:MM TD-DFT methods, allowing us to delineate the binding site of the ligands and to prove that the metal chelates neither decompose nor demetallate after uptake by HSA. The transport and delivery of the metal chelates by HSA in vivo is therefore feasible.

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Baseline characteristics of 31 healthy male U15 soccer players who were classified as select or non-select at the end of the season were compared. Players were 14.4 ± 0.54 years (13.6-15.3 years) at baseline; characteristics included body size, proportions and composition, estimated maturity status, several functional capacities, and coach classifications of potential in the sport. Decisions regarding selection or non-selection were made about two months after baseline. Select and non-select U15 soccer players differed significantly in estimated maturity status, body size, proportions and estimated muscle mass, functional tests related to speed, power and strength, and coach evaluation of potential, specifically tactical skills on offense and skills associated with creativity and decision making. When age and biological maturity status were statistically controlled, select and non-select players differed significantly only on the vertical jump, grip strength, and coach ratings of tactical skills on offense and of creativity and decision making. Results of stepwise discriminant analysis highlighted the importance of coach evaluation of tactical skills associated with offense, and of power and strength in distinguishing select from non-select players. The results highlight the advantages of advanced biological maturity status among adolescent male soccer players and also the importance of coach perceptions of talent. The latter implies a need for further study of the basis of coach perceptions, specifically how they are influenced by and perhaps interact with player characteristics at different ages, and how the perceptions influence playing time and player behaviors and interactions.

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The synthesis and reactivity of a novel class of clickable nucleotide analogues containing a C-phosphonate subunit that has an alkyne group at the terminal position of the oligophosphate chain are reported. The C-phosphonate subunits were prepared by simple one- or two-step procedures using commercially available reagents. Nucleotides were prepared by MgCl2-catalyzed coupling reactions and then subjected to CuAAC reactions with various azide compounds to afford 5'-γ-labeled nucleoside triphosphates in excellent yields.

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Numerous biomolecules recognize the 7-methylguanosine cap structure present at the 5' ends of eukaryotic mRNAs. Photo-crosslinking is a valuable technique to study these interactions. We report three anti-reverse cap analogs containing a photo-activable nucleoside, 6-thioguanosine ((6S)G), that enable the synthesis of capped RNAs with (6S)G positioned exclusively as the first transcribed nucleotide. The effect of the 6-thioguanosine moiety on binding to the translation factor eIF4E and the efficiency of mRNA translation was determined. The utility of mRNAs with a (6S)G-modified cap in crosslinking experiments is shown by mapping the histone H4 cap-binding pocket.

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Equilibrium constants (log K) for substitution of coordinated H(2)O in aquacyanocobyrinic acid heptamethyl ester (aquacyanocobester, ACCbs) and aquacyano-stable yellow cobyrinic acid hexamethyl ester (aquacyano-stable yellow cobester, ACSYCbs), in which oxidation of the C5 carbon of the corrin interrupts the normal delocalized system of corrins, by neutral N-donor ligands (ammonia, ethanolamine, 2-methoxyethylamine, N-methylimidazole, and 4-methylpyridine) have been determined spectrophotometrically as a function of temperature. Log K values increase with the basicity of the ligand, but a strong compensation effect between ΔH and ΔS values causes a leveling effect. The aliphatic amines with a harder donor atom produce ΔH values that are more negative in their reactions with ACSYCbs than with ACCbs, while the softer, aromatic N donors produce more negative ΔH values with ACCbs than with ACSYCbs. Molecular modeling (DFT, M06L/SVP, and a quantum theory of atoms in molecules analysis of the electron density) shows that complexes of the aliphatic amines with SYCbs produce shorter and stronger Co-N bonds with less ionic character than the Co-N bonds of these ligands with the cobester. Conversely, the Co-N bond to the aromatic N donors is shorter, stronger, and somewhat less ionic in the complexes of the cobester than in those of the SYCbs. Therefore, the distinction between the harder Co(III) in ACSYCbs and softer Co(III) in ACCbs, reported previously for anionic ligands, is maintained for neutral N-donor ligands.

RESUMEN

In the title compound, 2C(10)H(18)N(+)·CO(3) (2-), the adamantan-1-aminium cation forms three N-H⋯O hydrogen bonds to three carbonate ions, resulting in a layer parallel to (001) with the adamantane groups located on its surface so that adjacent layers form only C-H⋯H-C contacts. The carbonate anions occupy special positions of 32 symmetry, whereas the adamantan-1-aminium cations occupy special positions of 3 symmetry.

RESUMEN

In the title compound, C(10)H(18)N(+)·C(2)H(3)O(2) (-), the ammonium H atoms of the cation are linked to three acetate anions via N-H⋯O hydrogen bonds, forming a chain structure extending along the b axis.