Cheminformatics Study on Structural and Bactericidal Activity of Latest Generation β-Lactams on Widespread Pathogens

Area of Science:

• Computational Chemistry
• Spectroscopy
• Microbiology

Background:

• Penicillins are crucial antibiotics, but understanding their molecular properties and mechanisms of action is vital for combating resistance.
• Vibrational spectroscopy and computational methods offer powerful tools for characterizing drug molecules and predicting their behavior.

Purpose of the Study:

• To report and assign Raman spectra for oxacillin, carbenicillin, and azlocillin using DFT.
• To investigate the chemical reactivity and bactericidal efficiency of these penicillins.
• To develop a novel SERS-based resistogram for bacterial identification and resistance profiling.

Main Methods:

• Density Functional Theory (DFT) calculations with B3LYP/6-31G(d) and 6-311+G(2d,p) basis sets.
• Molecular docking studies.
• Frontier Molecular Orbital (FMO) and Molecular Electrostatic Potential (MEP) analyses.
• Disk diffusion method for bactericidal activity testing.
• Surface-Enhanced Raman Spectroscopy (SERS) coupled with Principal Component Analysis (PCA).

Main Results:

• Complete assignment of normal modes for oxacillin, carbenicillin, and azlocillin Raman spectra.
• Correlation between FMO/MEP data and the observed bactericidal efficiency against Gram-positive and Gram-negative bacteria.
• Successful demonstration of SERS-PCA resistogram for *A. hydrophila*.

Conclusions:

• The study provides fundamental spectroscopic and computational data for key penicillins.
• Cheminformatics and vibrational spectroscopy can predict and explain antibiotic efficacy.
• The SERS-PCA resistogram offers a promising approach for rapid clinical diagnostics and antibiotic resistance monitoring.