Prabuddha Bhattacharya

Synthesis of benzochromenes and dihydrophenanthridines with helical motifs using Garratt–Braverman and Buchwald–Hartwig reactions

A simple strategy for the synthesis of 6H-benzo[c]chromenes and 5,6-dihydrophenanthridines through a judicious use of Garratt–Braverman (GB) cyclization and Buchwald–Hartwig (BH) coupling in moderate to good yield, has been reported. The uniqueness of the GB reaction is exemplified in providing the required biaryl intermediate which could be successfully converted to the target skeleton via functional group transformations followed by BH coupling. The presence of a dihydro-isofuran moiety assisted in inducing a helical motif in these molecules, which is also confirmed by single crystal X-ray structural analysis. The crystallographic data gives valuable insight into the role of the non-bonding interaction in regulating the helicity.

Asymmetric Garratt–Braverman Cyclization: A Route to Axially Chiral Aryl Naphthalene–Amino Acid Hybrids

We report the first example of a highly diastereoselective Garratt-Braverman cyclization leading to the synthesis of chiral aryl naphthalene-amino acid hybrids in excellent yields. The stereogenecity in the amino acid has induced high diastereoselectivity for the reaction. Computations based on density functional theory indicated a lower activation free energy barrier for the M isomer as compared to that for the P diastereomer (ΔΔG = 3.48 kcal/mol). Comparison of the recorded CD spectrum of the product with the calculated one also supported the preferential formation of the M diastereomer.

Design and synthesis of dual probes for detection of metal ions by LALDI MS and fluorescence: application in Zn(II) imaging in cells

A Label-Assisted Laser Desorption/Ionization (LALDI) technique has recently been applied to the detection of metal ions through a time of flight (TOF) mass spectrometric measurement. In this paper, we report the synthesis of two terpyridine based ligands L1 and L2 containing a pyrene moiety. The presence of the latter helped the ligand metal complex to desorb from the surface and ionize upon laser irradiation and finally show up in the TOF MS. Both ligands were able to detect Zn2+, Ni2+ and Co2+ ions while Cu2+, Fe2+ and Mg2+ remained LDI silent. Complexation with the ligands also caused a red fluorescence only with Zn2+ ions that allowed Zn2+ imaging in cells. Thus the pyrene moiety acted as a dual probe for metal ion detection exploiting both LALDI MS and fluorescence techniques.

Photochemical activation of enediyne warheads: A potential tool for targeted antitumor therapy

Spatial and temporal control over DNA cleavage by photoactivated enediynes can be complemented by additional factors such as the release of internal strain, chelation, pH changes, intramolecular H-bonds, and substituent effects. This review presents design and reactivity of photoactivated enediynes/enynes and analyses the chemical, biological, and photophysical challenges in their applications.

π-Stacking assisted redox active peptide–gallol conjugate: synthesis of a new generation of low-toxicity antimicrobial silver nanoparticles

In this study, we describe the rational design and synthesis of a redox-active petide–gallol conjugate and explore its application in the preparation of antimicrobial silver nanoparticles. Increase in acidity and redox activity of peptide–gallol compounds upon pi-stacking was predicted in silico. A representative phenyl alanine–glycine dipeptide–gallol conjugate was synthesized via click chemistry between N-propargyl dipeptide and azidomethyl pyrogallol. The enhanced redox properties of the conjugate were exemplified by rapid formation of silver nanoparticles (Ag NPs) at room temperature without the need of an external capping agent. The nanoparticles formed were found to exhibit prominent antifungal activity against Candida albicans NCIM 3471 along with robust biofilm eradication ability. Thus, our study established the hypothesis that rationally designed peptide–gallol conjugates can be used as biocompatible, redox-active moieties for in situ generation of non-toxic antimicrobial silver nanoparticles in a fast one pot chemical reduction method.

Chloramphenicol-borate/boronate complex for controlling infections by chloramphenicol-resistant bacteria

Increasing bacterial resistance to antibiotics is a pressing problem worldwide, with many health organisations prioritizing this issue. Whilst there is a desperate need for new effective antimicrobials, it is also important to understand the mechanisms and epidemiology of the resistant pathogens currently present in the community. Chloramphenicol is one such well known antibiotic which had lost its efficacy due to bacterial resistance. In this paper, we report the design, synthesis, and bio-studies of novel chloramphenicol-borate/boronate derivatives which showed the ability to control the infections caused by chloramphenicol-resistant bacteria. Activity profiling against P. aeruginosa strain EXR1 with catB gene indicated the inability of acetyl transferase to acetylate the chloramphenicol-borate/boronate complex, unlike chloramphenicol. Results obtained from the antimicrobial assays were further rationalized by molecular docking studies. The latter revealed that the probable reason for the enhanced antibacterial activity may be attributed to the change in the binding site of chloramphenicol-borate/boronate with chloramphenicol acetyl transferase (CAT) with respect to chloramphenicol itself. Hemolytic and genotoxic studies established the reduced toxicity of these synthetic derivatives with respect to chloramphenicol.

The Never-Ending Story of β-Lactams: Use as Molecular Scaffolds and Building Blocks

The β-lactam moeity has been rightfully regarded as one of the most privileged and useful heterocyclic skeletons for not only their paramount importance in the field of antibacterial therapautics, but also because of their role as chiral synthons towards the synthesis of other bioactive heterocycles. In this chapter, we primarily aim at discussing three major issues: Kinugasa reaction as a highly successful synthetic route for the synthesis of various β-lactams, employing the β-lactam moeity as building block in syntheis and finally using β-lactam as molecular scaffold. The chapter presents a concise account on the aforesaid aspects which highlights the immense significance of such skeletons in the overlapping domains of chemistry and biology.