Combined mass spectrometry and computational analysis of cyanine dyes and their structural analogues

Đapić, Irena; Kobetić, Renata; Kurutos, Atanas; Tandarić, Tana; Šoić, Ružica; Vianello, Robert (2026) Combined mass spectrometry and computational analysis of cyanine dyes and their structural analogues. RSC Advances, 16 (7). pp. 5770-5784. ISSN 2046-2069

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Abstract

Cyanine dyes are widely used in biological imaging and labelling, yet the influence of halide counterions on their gas-phase stability and fragmentation remains poorly understood. Here we report a combined high-resolution mass spectrometry and computational study of asymmetric monomethine cyanine dyes bearing one to four positive charges, explicitly elucidating the mechanistic role of halide ions. We demonstrate that iodide uniquely promotes stable gas-phase self-assembly of cyanine dyes, forming higher-order clusters up to pentamers, whereas bromide and chloride do not. Tandem MS reveals pronounced halide-dependent fragmentation energetics, with iodide-containing complexes displaying enhanced stability and distinct product-ion distributions. These iodide-dye anion–π interactions support prior evidence of enhanced dye cell membrane permeability and mitochondrial accumulation. Density functional theory calculations rationalize these observations by identifying an SN2-like halide-assisted C–N bond cleavage mechanism, most favorable for iodide, which governs key fragmentation pathways. By integrating MSn experiments with computational analysis, this work moves beyond descriptive fragmentation studies and provides a mechanistic framework for halide-mediated behavior of cyanine dyes, with implications for mass spectrometric characterization of cyanine-labelled biomolecules and related imaging probes.

Item Type:	Article
Uncontrolled Keywords:	mass spectrometry; computational DFT analysis; cyanine dyes
Subjects:	NATURAL SCIENCES > Chemistry
Divisions:	Division of Organic Chemistry and Biochemistry
Projects:	Project title Project leader Project code Project type Derivati cijaninskih boja – nove probe za nukleinske kiseline i bioprobe sa antitumorskim i antibakterijskim djelovanjem (rezultat rada na projektu) Marijana Radić Stojković IP-2024-05-7701 HRZZ Dizajn, sinteza i računalna analiza novih optičkih kemijskih pH osjetilnih derivata benzazola-BenzpHSens Robert Vianello; Marijana Hranjec; Ida Boček IP-2020-02-8090 HRZZ
Depositing User:	Ema Buhin Šaler
Date Deposited:	02 Feb 2026 09:26
URI:	http://fulir.irb.hr/id/eprint/11204
DOI:	10.1039/d5ra07246h

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