Structural characterization by NMR of rifabutinol, a derivative of rifabutin

Specific Interactions between Rifamycin Antibiotics and Water Influencing Ability To Overcome Natural Cell Barriers and the Range of Antibacterial Potency

“…Due to the repulsion of the negatively charged centers after the hypothetical deprotonation, the presence of the analogous zwitterionic form would be unfavorable for RFB (Figure S1). The nonionic structure of RFB is confirmed by a chemical shift of the C(8) signal in the 13 C NMR spectrum (δ C(8) < 170 ppm, Figure 2a) and the position of the O(8)H signal at δ = ∼15 or at δ = ∼16 ppm in CDCl 3 and in DMSO-d 6 +H 2 O, respectively (Figure 2a,b, Tables S3 and S4). The next step in our studies was to determine the conformation of the ansa-bridge in the studied rifamycins.…”

“…The close proximity of the C(8) and C(11) carbon atom signals indicates a strong conjugation effect in the zwitterion, extending from the deprotonated phenol O(8)H to C(11)O group. Thus, according to 13 C NMR spectra (Figure 2a), RMP and RFP exist in solution in the nonionic form in CDCl 3 or zwitterionic form in DMSO-d 6 +H 2 O. In turn, RFX exists exclusively in the zwitterionic form and RFB, exclusively in the nonionic form, irrespective of the solvent used and the presence of water molecules in the solution (Figure 2a, Tables S2 and S4).…”

“…The presence of C(8) and C( 11) carbon resonances below 170 and above 190 ppm in 13 C NMR spectra, respectively, provides evidence for a nonionic form of antibiotics with a C(11)O ketone group and a phenol at C(8) (Figures 1 and 2a). In the case of a proton transfer from the most acidic phenol O(8)H to the most basic center within rifamycins, the C(8) and C(11) carbon atom signals appear together in the range of 180−190 ppm (Figures 1 and 2a).…”

“…Proton Transfer and ansa-Bridge Arrangement for Rifamycin Type Antibiotics. To reveal the structure of the ansa-bridge in different solvents for RMP, RFP, RFX, and RFB, 1 H, 13 C, and 15 N NMR spectra, supported by 2D NMR experiments ( 1 H− 1 H COSY; 1 H− 13 C HSQC; 1 H− 15 N HSQC; 1 H− 13 C HMBC; 1 H− 1 H NOESY), and FT-IR spectra were recorded (Figures 2 and 3, Tables S1−S4).…”

“…11 Semisynthetic ansa-macrolides such as rifabutin (RFB), rifapentine (RFP), rifampicin (also called rifampin (RMP)), and rifaximin (RFX) (Figure 1) belong to a widely used class of antibiotics. 12 Their unique basket-like structure formed by a structural motif called "ansa-bridge" was extensively studied by NMR spectroscopy in nonpolar solutions 13 and theoretical 14 and X-ray 15 methods (Figure 1). These rifamycin-type antibiotics have identical structures of the ansa-bridge, a comparable aromatic core, and relatively strong organic bases at the C(3) or C(3)−C(4) arm (Figure 1).…”