1188-95-0

Extraction and binding studies of [PtCl6]2- are reported for 24 mono-, bi-, and tripodal extractants containing tris(2-Aminoethyl)amine (TREN) or tris(3-Aminopropyl)amine (TRPN) scaffolds. These reagents are designed to recognize the outer coordination sphere of [PtCl6]2- and to show selectivity over chloride anion under acidic conditions. Extraction from 0.6 M HCl involves protonation of the N-center in tertiary amines containing one, two, or three urea, amide, or sulfonamide hydrogen-bond donors to set up the following equilibrium: 2L(org) + 2H+ + [PtCl6]2- [(LH)2PtCl6](org). All reagents show higher Pt loading than trioctylamine, which was used as a positive control to represent commercial trialkylamine reagents. The loading of [PtCl6]2- depends on the number of pendant amides in the extractant and follows the order tripodal > bipodal > monopodal, with urea-containing extractants outperforming amide and sulfonamide analogues. A different series of reagents in which one, two, or three of the alkyl groups in tris-2-ethylhexylamine are replaced by 3-N′-hexylpropanamide groups all show a comparably high affinity for [PtCl6]2- and high selectivity over chloride anion in extractions from aqueous acidic solutions. 1H NMR titration of three extractants [LH·Cl] with [(Oct4N)2PtCl6] in CDCl3 provides evidence for high selectivity for [PtCl6]2- over chloride for tri-and bipodal extractants, which show higher binding constants than a monopodal analogue.

The competitive substitution of the anion (A-) in contact ion pairs of the type [Oct3NH+]B(C6F5V by unsaturated hydrocarbons (L) in accordance with the equilibrium Oct 3NH+ ...A- + nL ? [Oct 3NH+-Ln]A- has been studied in CCl4. On the basis of equilibrium constants, K, and shifts of vNH to low frequency, it has been established that complexed Oct3NH +-L., cations with n = 1 and 2 are formed and have unidentate and bifurcated N-H+...μ hydrogen bonds, respectively. Bifurcated hydrogen bonds to unsaturated hydrocarbons have not been observed previously. The unsaturated hydrocarbons studied include benzene and methylbenzenes, fused-ring aromatics, alkenes, conjugated dienes, and alkynes. From the magnitude of the redshifts in the N-H stretching frequencies, AvNH, a new scale for ranking the It basicity of unsaturated hydrocarbons is proposed: fused-ring aromatics ≤ benzene +... μ hydrogen bonding in proteins and molecular crystals.

Drug resistant bacteria have emerged, so robust methods are needed to evaluate combined activities of known antibiotics as well as new synthetic compounds as novel antimicrobial agents to treatment efficacy in severe bacterial infections. Marine natural products (MNPs) have become new strong leads in the drug discovery endeavor and an effective alternative to control infections. Herein, we report the bioassay guided fractionation of marine extracts from the sponges Lendenfeldia, Ircinia, and Dysidea that led us to identify novel compounds with antimicrobial properties. Chemical synthesis of predicted compounds and their analogs has confirmed that the proposed structures may encode novel chemical structures with promising antimicrobial activity against the medically important pathogens. Several of the synthetic analogs exhibited potent and broad spectrum in vitro antibacterial activity, especially against the Methicillin-resistant Staphylococcus aureus (MRSA) (MICs to 12.5 μM), Mycobacterium tuberculosis (MICs to 0.02 μM), uropathogenic Escherichia coli (MIC o 6.2 μM), and Pseudomonas aeruginosa (MIC to 3.1 μM). Checkerboard assay (CA) and time-kill studies (TKS) experiments analyzed with the a pharmacodynamic model, have potentials for in vitro evaluation of new and existing antimicrobials. In this study, CA and TKS were used to identify the potential benefits of an antibiotic combination (i.e., synthetic compounds, vancomycin, and rifampicin) for the treatment of MRSA and M. tuberculosis infections. CA experiments indicated that the association of compounds 1a and 2a with vancomycin and compound 3 with rifampicin combination have a synergistic effect against a MRSA and M. tuberculosis infections, respectively. Furthermore, the analysis of TKS uncovered bactericidal and time-dependent properties of the synthetic compounds that may be due to variations in hydrophobicity and mechanisms of action of the molecules tested. The results of cross-referencing antimicrobial activity, and toxicity, CA, and Time-Kill experiments establish that these synthetic compounds are promising potential leads, with a favorable therapeutic index for antimicrobial drug development.