Synthesis, Physicochemical Characterization, and Biocidal Evaluation of Three Novel Aminobenzoic Acid-Derived Schiff Bases Featuring Intramolecular Hydrogen Bonding

Carreño, Alexander; Artigas, Vania; Gómez-Arteaga, Belén; Ancede-Gallardo, Evys; Cepeda-Plaza, Marjorie; Martínez-Araya, Jorge I.; Arce, Roxana; Gacitúa, Manuel; Videla, Camila; Preite, Marcelo; Otero, María Carolina; Guerra, Catalina; Polanco, Rubén; Fuentes, Ignacio; Marchant, Pedro; Inostroza, Osvaldo; Gil, Fernando; Fuentes, Juan A.

doi:10.3390/ijms262110801

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Synthesis, Physicochemical Characterization, and Biocidal Evaluation of Three Novel Aminobenzoic Acid-Derived Schiff Bases Featuring Intramolecular Hydrogen Bonding

by

Alexander Carreño

^1,2,*

,

Vania Artigas

²,

Belén Gómez-Arteaga

²,

Evys Ancede-Gallardo

²

,

Marjorie Cepeda-Plaza

¹,

Jorge I. Martínez-Araya

¹,

Roxana Arce

^1,3

,

Manuel Gacitúa

⁴

,

Camila Videla

^2,5,

Marcelo Preite

⁶,

María Carolina Otero

⁵

,

Catalina Guerra

⁷,

Rubén Polanco

⁷,

Ignacio Fuentes

^8,9

,

Pedro Marchant

⁸,

Osvaldo Inostroza

^10,11

,

Fernando Gil

^10,11

and

Juan A. Fuentes

^8,*

¹

Departamento de Ciencias Químicas, Facultad de Ciencias Exactas, Universidad Andres Bello, Av. República 275, Santiago 8370146, Chile

²

Laboratorio de Síntesis Organometálica, Centro de Nanociencias Aplicadas (CANS), Facultad de Ciencias Exactas, Universidad Andres Bello, Av. República 330, Santiago 8370186, Chile

³

Millennium Institute on Green Ammonia as Energy Vector (MIGA), Av. Vicuña Mackenna 4860, Macul, Santiago 7820436, Chile

⁴

Facultad de Ingeniería y Ciencias, Universidad Diego Portales, Ejército 441, Santiago 8370191, Chile

⁵

Escuela de Química y Farmacia, Facultad de Medicina, Universidad Andres Bello, Sazié 2320, Santiago 7591538, Chile

⁶

Departamento de Química Orgánica, Facultad de Química y de Farmacia, Pontificia Universidad Católica de Chile, Av. Vicuña Mackenna 4860, Santiago 7820436, Chile

⁷

Laboratorio de Hongos Fitopatógenos, Centro de Biotecnología Vegetal (CBV), Facultad de Ciencias de la Vida, Universidad Andres Bello, Av. República 330, Santiago 8370186, Chile

⁸

Laboratorio de Genética y Patogénesis Bacteriana, Centro de Investigación de Resiliencia a Pandemias, Facultad de Ciencias de la Vida, Universidad Andres Bello, República 330, Santiago 8370186, Chile

⁹

Doctorado en Biotecnología, Facultad de Ciencias de la Vida, Universidad Andrés Bello, República 330, Santiago 8370186, Chile

¹⁰

School of Medicine, Faculty of Medicine, Universidad de los Andes, Santiago 7620001, Chile

¹¹

Microbiota-Host Interactions & Clostridia Research Group, Center for Biomedical Research and Innovation (CIIB), Universidad de los Andes, Av. Monseñor Álvaro del Portillo 12455, Santiago 7620001, Chile

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^*

Authors to whom correspondence should be addressed.

Int. J. Mol. Sci. 2025, 26(21), 10801; https://doi.org/10.3390/ijms262110801

Submission received: 25 September 2025 / Revised: 25 October 2025 / Accepted: 28 October 2025 / Published: 6 November 2025

(This article belongs to the Special Issue Feature Papers in ‘Physical Chemistry and Chemical Physics’: Fourth Edition)

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Abstract

Metal-free aminobenzoic acid-derived Schiff bases are attractive antimicrobial leads because their azomethine (–C=N–) functionality enables tunable electronic properties and target engagement. We investigated whether halogenation on the phenolic ring would modulate the redox behavior and enhance antibacterial potency, and hypothesized that heavier halogens would favorably tune physicochemical and electronic descriptors. We synthesized three derivatives (SB-3/Cl, SB-4/Br, and SB-5/I) and confirmed their structures using FTIR, ¹H- and ¹³C-NMR, UV-Vis, and HRMS. For SB-5, single-crystal X-ray diffraction and Hirshfeld analysis verified the intramolecular O–H···N hydrogen bond and key packing contacts. Cyclic voltammetry revealed an irreversible oxidation (aminobenzoic ring) and, for the halogenated series, a reversible reduction associated with the imine; peak positions and reversibility trends are consistent with halogen electronic effects and DFT-based MEP/LHS descriptors. Antimicrobial testing showed that SB-5 was selectively potent against Gram-positive aerobes, with low-to-mid micromolar MICs across the panel. Among anaerobes, activity was more substantial: Clostridioides difficile was inhibited at 0.1 µM, and SB-3/SB-5 reduced its sporulation at sub-MICs, while Blautia coccoides was highly susceptible (MIC 0.01 µM). No activity was detected against Gram-negative bacteria at the tested concentrations. In the fungal assay, Botrytis cinerea displayed only a transient fungistatic response without complete growth inhibition. In mammalian cells (HeLa), the compounds displayed clear concentration-dependent behavior . Overall, halogenation, particularly iodination, emerges as a powerful tool to couple redox tuning with selective Gram-positive activity and a favorable cellular tolerance window, nominating SB-5 as a promising scaffold for further antimicrobial optimization.

Keywords: Schiff bases; aminobenzoic acid; intramolecular hydrogen bonding; biocidal activity; hela cell viability; cyclic voltammetry; X-ray crystallography; MEP; LHS

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MDPI and ACS Style

Carreño, A.; Artigas, V.; Gómez-Arteaga, B.; Ancede-Gallardo, E.; Cepeda-Plaza, M.; Martínez-Araya, J.I.; Arce, R.; Gacitúa, M.; Videla, C.; Preite, M.; et al. Synthesis, Physicochemical Characterization, and Biocidal Evaluation of Three Novel Aminobenzoic Acid-Derived Schiff Bases Featuring Intramolecular Hydrogen Bonding. Int. J. Mol. Sci. 2025, 26, 10801. https://doi.org/10.3390/ijms262110801

AMA Style

Carreño A, Artigas V, Gómez-Arteaga B, Ancede-Gallardo E, Cepeda-Plaza M, Martínez-Araya JI, Arce R, Gacitúa M, Videla C, Preite M, et al. Synthesis, Physicochemical Characterization, and Biocidal Evaluation of Three Novel Aminobenzoic Acid-Derived Schiff Bases Featuring Intramolecular Hydrogen Bonding. International Journal of Molecular Sciences. 2025; 26(21):10801. https://doi.org/10.3390/ijms262110801

Chicago/Turabian Style

Carreño, Alexander, Vania Artigas, Belén Gómez-Arteaga, Evys Ancede-Gallardo, Marjorie Cepeda-Plaza, Jorge I. Martínez-Araya, Roxana Arce, Manuel Gacitúa, Camila Videla, Marcelo Preite, and et al. 2025. "Synthesis, Physicochemical Characterization, and Biocidal Evaluation of Three Novel Aminobenzoic Acid-Derived Schiff Bases Featuring Intramolecular Hydrogen Bonding" International Journal of Molecular Sciences 26, no. 21: 10801. https://doi.org/10.3390/ijms262110801

APA Style

Carreño, A., Artigas, V., Gómez-Arteaga, B., Ancede-Gallardo, E., Cepeda-Plaza, M., Martínez-Araya, J. I., Arce, R., Gacitúa, M., Videla, C., Preite, M., Otero, M. C., Guerra, C., Polanco, R., Fuentes, I., Marchant, P., Inostroza, O., Gil, F., & Fuentes, J. A. (2025). Synthesis, Physicochemical Characterization, and Biocidal Evaluation of Three Novel Aminobenzoic Acid-Derived Schiff Bases Featuring Intramolecular Hydrogen Bonding. International Journal of Molecular Sciences, 26(21), 10801. https://doi.org/10.3390/ijms262110801

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Synthesis, Physicochemical Characterization, and Biocidal Evaluation of Three Novel Aminobenzoic Acid-Derived Schiff Bases Featuring Intramolecular Hydrogen Bonding

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