Kuanysh Kabytaev

Carborane-derived local anesthetics are isomer dependent.

Clinically there is a need for local anesthetics with a greater specificity of action on target cells and longer duration. We have synthesized a series of local anesthetic derivatives we call boronicaines in which the aromatic phenyl ring of lidocaine was replaced with ortho‐, meta‐, C,C’‐dimethyl meta‐ and para‐carborane clusters. The boronicaine derivatives were tested for their analgesic activity and compared with lidocaine using standard procedures in mice following a plantar injection. The compounds differed in their analgesic activity in the following order: ortho‐carborane = C,C’‐dimethyl meta‐carborane > para‐carborane > lidocaine > meta‐carborane derivative. Both ortho‐boronicaine and C,C’‐dimethyl meta‐boronicaine had longer durations of analgesia than lidocaine. Differences in analgesic efficacies are rationalized by variations in chemical structure and protein binding characteristics.

Novel Synthetic Approach to Charge-Compensated Phosphonio- nido-Carboranes. Synthesis and Structural Characterization of Neutral Mono and Bis(Phosphonio) nido-ortho-Carboranes

A number of monosubstituted n-(triphenylphosphonio)-7,8-dicarba-nido-undecaboranes (2a, n = 1; 2b, n = 3; 2c, n = 5; 2d, n = 9) were prepared via a cross-coupling reaction between the tetrabutylammonium iodo-7,8-dicarba-nido-undecaborates (1a-d) and PPh3 in the presence of a Pd(PPh3)4 catalyst. The substitution rate was found to depend on the iodine position in the carborane cage. Under similar conditions, the reaction of 5,6-diiodo- (3) and 9,11-diiodo-7,8-dicarba-nido-undecaborate (5) anions exclusively yielded the monosubstitution products 5-iodo-6-(triphenylphosphonio)-7,8-dicarba-nido-undecaborane (4) and 9-iodo-11-(triphenylphosphonio)-7,8-dicarba-nido-undecaborane (6), respectively. The reaction of tetrabutylammonium 6,9-diiodo-7,8-dicarba-nido-undecaborate (7) exclusively produced the phosphine substitution product in the open face of the nido-carborane, 6-iodo-9-triphenylphosphonio-7,8-dicarba-nido-undecaborane (8). The addition of a base (Cs2CO3, NaH) to the reactions of 3 and 5 with PPh3 afforded the corresponding bis(triphenylphosphonio)-7,8-dicarba-nido-undecaboranes, 9 and 10. Compound 10 was also prepared from 6 using the general procedure. The reaction of the triiodocarborane tetrabutylammonium 5,6,9-triiodo-7,8-dicarba-nido-undecaborate (11) with excess PPh3 in the presence of Cs2CO3 and Pd(PPh3)4 only produced neutral 5-iodo-6,9-bis(triphenylphosphonio)-7,8-dicarba-nido-undecaborane (12); no positively charged tris(phosphonio) species formed. The compositions of all prepared compounds were determined by multinuclear NMR spectroscopy and high-resolution mass spectrometry. The structures of compounds 2c, 6, 8, 9, and 12 were established by the X-ray diffraction analysis of single crystals.

Higher degree of glycation of hemoglobin S compared to hemoglobin A measured by mass spectrometry: Potential impact on HbA1c testing

BACKGROUND Glycated hemoglobin (GHb), reported as HbA1c, is used as marker of long-term glycemia for diabetic patients. HbA1c results from boronate affinity methods are generally considered to be unaffected by most hemoglobin variants; this assumes comparable glycation of variant and non-variant (HbAA) hemoglobins. In this report, glycation of HbA beta chain (βA) and HbS beta chain (βS) for the most common Hb variant trait (HbAS) are examined. METHODS We analyzed 41 blood samples from subjects with HbAS, both with and without diabetes. Using LC-MS, ratios of glycated HbS to glycated HbA were determined by comparison of areas under the curves from extracted ion chromatograms. RESULTS Glycation of βS chains was significantly higher (p<0.001) than βA chains; this difference was consistent across subjects. Total (α+β) glycated HbAS was theoretically estimated to be ~5% higher than glycated HbAA. CONCLUSION This novel mass-spectrometric approach described allows for relative quantification of glycated forms of βS and βA. Although βS glycation was significantly higher than that of βA, the difference in total glycation of HbAS versus HbAA was smaller and unlikely to impact clinical interpretation of boronate affinity HbA1c results. These data support the continued use of boronate affinity to measure HbA1c in patients with HbAS.

Implementing a Reference Measurement System for C-Peptide: An Addendum

To the Editor: In a recent study by Little et al. (1), the story of C-peptide standardization was left somewhat uncertain with the problem of 2 reference methods providing different C-peptide concentrations. Although very well correlated ( r 2 = 0.986), there was a bias of approximately 20% between the Diabetes Diagnostic Laboratory (DDL)1 method (operated in 2 different laboratories in the US) and the National Metrology Institute of Japan (NMIJ; y = 0.7824x − 0.0202). There were differences in the procedures and in the labeled internal standards (ISs). The NMIJ method was traceable to the NMIJ Certified Reference Material (6901-b) (2), whereas the DDL method was traceable to the IS developed in Dr. Steins Laboratory in …