4-Hydroxythiobenzamide

Long-term release of a thiobenzamide from a backbone functionalized poly(lactic acid).[Pubmed:26870159]

Polym Chem. 2015 Oct;6(40):7188-7195.

Hydrogen sulfide is emerging as a critically important molecule in medicine, yet there are few methods for the long-term delivery of molecules that degrade to release H2S. In this paper the first long-term release of a thiobenzamide that degrades to release H2S is described. A series of polymers were synthesized by the copolymerization of L-lactide and a lactide functionalized with 4-Hydroxythiobenzamide. A new method to attach functional groups to a derivative of L-lactide is described based on the addition of a thiol to an alpha,beta-unsaturated lactide using catalytic I2. This reaction proceeded under mild conditions and did not ring-open the lactone. The copolymers had molecular weights from 8 to 88 kg mol(-1) with PDIs below 1.50. Two sets of microparticles were fabricated from a copolymer; the average diameters of the microparticles were 0.53 and 12 mum. The degradation of the smaller microparticles was investigated in buffered water to demonstrate the slow release of thiobenzamide over 4 weeks. Based on the ability to synthesize polymers with different loadings of thiobenzamide and that thiobenzamide is a known precursor to H2S, these particles provide a polymer-based method to deliver H2S over days to weeks.

Synthesis and Pharmacological Evaluation of Novel Adenine-Hydrogen Sulfide Slow Release Hybrids Designed as Multitarget Cardioprotective Agents.[Pubmed:26809888]

J Med Chem. 2016 Mar 10;59(5):1776-90.

This work deals with the design, synthesis, and evaluation of the cardioprotective properties of a number of novel hybrid compounds combining the adenine nucleus with a suitable H2S slow-releasing moiety, coupled via a stable ether bond. The H2S release rate of the hybrids and their ability to increase cGMP were estimated in vitro. The most promising derivatives 4 and 11, both containing 4-Hydroxythiobenzamide moiety as H2S donor, were selected for further in vivo evaluation. Their ability to release H2S in vivo was recorded using a new fully validated UPLC-DAD method. Both compounds reduced significantly the infarct size when administered at the end of sustained ischemia. Mechanistic studies showed that they conferred enhanced cardioprotection compared to adenine or 4-Hydroxythiobenzamide. They activate the PKG/PLN pathway in the ischemic myocardium, suggesting that the combination of both pharmacophores results in synergistic cardioprotective activity through the combination of both molecular pathways that trigger cardioprotection.

Vibrational spectra, NBO, HOMO-LUMO and conformational stability studies of 4-hydroxythiobenzamide.[Pubmed:25827766]

Spectrochim Acta A Mol Biomol Spectrosc. 2015 Aug 5;147:51-66.

In this work, the experimental and theoretical study on molecular structure, vibrational spectral analysis of 4-Hydroxythiobenzamide (HTB) have been reported. The solid phase FTIR (4000-400 cm(-1)) and FT-Raman spectra (3500-50 cm(-1)) were recorded. The molecular geometry, harmonic vibrational frequencies and bonding features of HTB in the ground-state have been calculated by the density functional method (B3LYP) with 6-311+G(d,p) and 6-311++G(d,p) as basis sets. Utilizing the observed FTIR and FT-Raman data, a complete vibrational assignment and analysis of the fundamental modes of the compound were carried out. Stability of the molecule arising from hyperconjugative interactions, charge delocalization has been analyzed using natural bond orbital (NBO) analysis. The results show that the value of electron density (ED) in the sigma( *) antibonding orbitals and E((2)) energies confirms the occurrence of ICT (intra-molecular charge transfer) within the molecule. The UV spectrum was measured in ethanol solution. The energy and oscillator strength calculated by time-dependent density functional theory (TD-DFT) correlates with the experimental findings. The calculated molecular electrostatic potential (MESP), HOMO and LUMO energies show that charge transfer occurs within the molecule. Besides, the simulated infrared and Raman spectra of the title compound which show good agreement with observed spectra.