Interchange of L‑, Z‑, and Bound-Ion-Pair X‑Type Ligation on Cadmium Selenide Quantum Belts

Wurtzite CdSe quantum belts (QBs) having Z-type ligation, such as {CdSe­[Cd­(oleate)2]0.19} QBs, undergo a facile ligation exchange with AX salts (A = R4N, Na; X = OH, Cl, Br, NO3, OBz, OAc) to afford QBs having bound-ion-pair X-type ligation and empirical formulas CdSe­[X]x[A]x. The exchange to AX ligation is accompanied by shifts of the quantum-belt absorption spectra by as large as 340 meV (for X = OH) relative to the spectrum of L-type {CdSe­[n-octylamine]0.53} QBs. AX ligation is also investigated using the Na+ salts of d- and l-phenylalanine. These chiral X ligands induce inverse chiroptical effects in the circular dichroism spectra corresponding to the electronic transitions of the CdSe QBs, providing a strong evidence of the direct ligation of the X groups on the QB surfaces. AX ligation appears to consist of two populations on the QBs, one for which the AX ligands are persistently bound and another for which the AX ligands are readily removed by washing. These generate two ligation stoichiometries referred to as depleted and saturated ligation. The empirical formulas for the depleted ligation are in the approximate range of CdSe­[X]0.1–0.3[A]0.1–0.3, whereas those for saturated ligation are in the approximate range of CdSe­[X]0.4–0.8[A]0.4–0.8. These ranges are consistent with approximately one and two X– ligands per three-coordinate surface Cd atom. AX ligation is readily exchanged to either L-type primary amine or Z-type Cd­(oleate)2 ligation. However, AX salts do not displace L-type primary amine ligation under the conditions studied. All ligation exchanges are rapid and complete at room temperature, and with the exception of L-type to bound-ion-pair X-type ligation, fully reversible

Synthesis of [3,4-¹³C₂]-Enriched Bile Salts as NMR Probes of Protein−Ligand Interactions

Synthetic methodology that allows for incorporation of isotopic carbon at the C-3 and C-4 positions of bile salts is reported. Three [3,4-13C2]-enriched bile salts were synthesized from either deoxycholic or lithocholic acid. The steroid 3α-OH group was oxidized and the A-ring was converted into the Δ4-3-ketone. The C-24 carboxylic acid was next converted into the carbonate group and selectively reduced to the alcohol in the presence of the A-ring enone. Following protection of the 24-OH group, the Δ4-3-ketone was converted into the A-ring enol lactone. Condensation of the enol lactone with [1,2-13C2]-enriched acetyl chloride and subsequent Robinson annulation afforded a [3,4-13C2]-enriched Δ4-3-ketone that was subsequently converted back into a 3α-hydroxy-5β-reduced bile steroid. C-7 hydroxylation, when necessary, was achieved via conversion of the Δ4-3-ketone into the corresponding Δ4,6-dien-3-one, epoxidation of the Δ6-double bond, and hydrogenolysis/hydrogenation of the 5,6-epoxy enone system. The [3,4-13C2]-enriched bile salts were subsequently complexed to human ileal bile acid binding protein (I-BABP), and 1H-13C HSQC spectra were recorded to show the utility of the compounds for investigating the interactions of bile acids with I-BABP

Palladium-Catalyzed Potassium Enoxyborate Alkylation of Enantiopure Hajos−Parrish Indenone To Construct Rearranged Steroid Ring Systems

Here we report the stereo- and regiospecific C-6 alkylation of a trans-inden-5-one (from optically pure Hajos−Parrish ketone) with allylic electrophiles. Use of this alkylation procedure has led to an improved synthesis of the benz[f]indene ring system and the first enantiospecific total syntheses of the cyclopenta[b]anthracene and cyclopenta[b]phenanthrene ring systems (two synthetic routes)

Palladium-Catalyzed Potassium Enoxyborate Alkylation of Enantiopure Hajos−Parrish Indenone To Construct Rearranged Steroid Ring Systems

Here we report the stereo- and regiospecific C-6 alkylation of a trans-inden-5-one (from optically pure Hajos−Parrish ketone) with allylic electrophiles. Use of this alkylation procedure has led to an improved synthesis of the benz[f]indene ring system and the first enantiospecific total syntheses of the cyclopenta[b]anthracene and cyclopenta[b]phenanthrene ring systems (two synthetic routes)

Palladium-Catalyzed Potassium Enoxyborate Alkylation of Enantiopure Hajos−Parrish Indenone To Construct Rearranged Steroid Ring Systems

Here we report the stereo- and regiospecific C-6 alkylation of a trans-inden-5-one (from optically pure Hajos−Parrish ketone) with allylic electrophiles. Use of this alkylation procedure has led to an improved synthesis of the benz[f]indene ring system and the first enantiospecific total syntheses of the cyclopenta[b]anthracene and cyclopenta[b]phenanthrene ring systems (two synthetic routes)

Structural Features Responsible for the Biological Stability of <i>Histoplasma</i>’s Virulence Factor CBP

The virulence factor CBP is the most abundant protein secreted by Histoplasma capsulatum, a pathogenic fungus that causes histoplasmosis. Although the biochemical function and pathogenic mechanism of CBP are unknown, quantitative Ca2+ binding measurements indicate that CBP has a strong affinity for calcium (KD = 6.45 ± 0.4 nM). However, no change in structure was observed upon binding of calcium, prompting a more thorough investigation of the molecular properties of CBP with respect to self-association, secondary structure, and stability. Over a wide range of pH values and salt concentrations, CBP exists predominantly as a stable, noncovalent homodimer in both its calcium-free and -bound states. Solution-state NMR and circular dichroism (CD) measurements indicated that the protein is largely α-helical, and its secondary structure content changes little over the range of pH values encountered physiologically. ESI-MS revealed that the six cysteine residues of CBP are involved in three intramolecular disulfide bonds that help maintain a highly protease resistant structure. Thermally and chemically induced denaturation studies indicated that unfolding of disulfide-intact CBP is reversible and provided quantitative measurements of protein stability. This disulfide-linked, protease resistant, homodimeric α-helical structure of CBP is likely to be advantageous for a virulence factor that must survive the harsh environment within the phagolysosomes of host macrophages

Isothermal titration calorimetry reveals step-wise binding of DARC to DBP-RII in solution.

<p>(<b>A</b>) A biphasic binding profile is observed indicating the formation of the heterotrimer at a molar ratio of 0.5 (<i>n₁</i> = 0.44±0.02, <i>K_d1</i> = 2183±125 nM, Δ<i>H₁</i> = −2663±69 cal/mol) and heterotetramer at a molar ratio of 1 (<i>n₂</i> = 0.50±0.02, <i>K_d2</i> = 88.5±26.6 nM, Δ<i>H₂</i> = −3338±23 cal/mol). The fit to the two independent site binding model is shown as a red line. Molar ratios are expressed as monomers of DBP-RII. Open circles denote unbound DBP, closed circles denote bound DBP. Titration of (<b>B</b>) PBS into DBP and (<b>C</b>) DARC into PBS reveals no observable profiles demonstrating the biphasic profile is due to DARC binding to DBP. In all cases, the top panel contains raw binding data, and the bottom panel changes in enthalpy associated with binding.</p

Residues 14–43 of DARC contain the minimal binding region.

<p>¹H-¹⁵N-TROSY spectra of unbound DARC 1–60 (black) overlaid on ¹H-¹⁵N-TROSY spectra of DARC 1–60 in the presence of excess unlabelled DBP-RII (red). Sequence assignments are shown for the unbound DARC ¹H-¹⁵N-TROSY spectra. Peaks still visible in the presence of DBP-RII (red) are at DARC 1–60's N- and C- termini. Residues that disappear in the presence of DBP-RII are in the center of DARC and delineate the binding region.</p

Heterotrimer interface residues determined by PDBePISA [47]: All residues in the interface are listed sequentially and do not indicate interacting pairs.

<p>Heterotrimer interface residues determined by PDBePISA <a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1003869#ppat.1003869-Krissinel1" target="_blank">[47]</a>: All residues in the interface are listed sequentially and do not indicate interacting pairs.</p

Crystal Structure of the DBP-RII∶DARC heterotrimer and heterotetramer.

<p>Overview of (<b>A</b>) DBP-RII∶DARC heterotrimer and (<b>B</b>) the DBP-RII∶DARC heterotetramer. Rotated views, (<b>C</b>) and (<b>D</b>), show DARC helices are oriented in parallel in the heterotetramer. DBP-RII monomers are in yellow and green. DARC monomers are in purple and blue.</p