ORIGINAL RESEARCH Structural analysis and probing the conformational space of dansylamide by means of gas-phase electron diffraction and quantum chemistry Marwan Dakkouri 1 & Georgiy Girichev 2 & Nina Giricheva 3 & Vjacheslav Petrov 3 & Valentina Petrova 2 Received: 27 February 2018 /Accepted: 5 April 2018 # Springer Science+Business Media, LLC, part of Springer Nature 2018 Abstract Dansylamide is perhaps the most ubiquitous fluorophore due to its donor-acceptor bifunctionality and its ability to form intra- and intermolecular hydrogen bonding. Among the diversity of its applications is the development of new generation of biosensors for the in vivo monitoring of traces of metals. The structure and conformational stability of dansylamide in the gas phase were investigated for the first time by a combined gas-phase electron diffraction-mass spectrometry (GED/MS), complemented by quantum chemical calculations. GED data indicate that different skewed conformers exist at T = 464 K, which are characterized by the deviation of two S–N bonds from the perpendicular orientation relative to the naphthalene plane. Maybe the most indicative structural parameters for electronic interactions between the donor-acceptor substituents and the aromatic naphthalene and the subsequent stabilization of the favorable skewed eclipsed-syn conformer are the dihedral angles C 9 –C 1 –S–N and C 10 – C 5 –N–C with the experimentally determined values of 66.8° (32) and 68.1° (72), respectively. The role of –SO 2 NH 2 by forming intramolecular hydrogen bonds was scrutinized by employing the natural bond orbital approach (NBO), quantum theory atoms in molecules (QTAIM), and molecular electrostatic potential (MESP). The non-planarity of the naphthalene skeleton due to the electronic interactions with the substituents and its consequence for the fluorescence activity of dansylamide have been discussed. Keywords Structure conformation . H-bond . NBO . QTAIM . MESP . Ring non-planarity Introduction Dansylamide (CH 3 ) 2 N – C 10 Н 6 – SO 2 NH 2 (5-(dimethylamino)naphthalene-1-sulfonamide) is used in biochemistry and medicine for fluorescent labeling of biolog- ical compounds in order to trace their activities, e.g., in an enzyme system for transferring certain information [1]. Applying the fluorescence-activated cell sorting (FACS) tech- nique, Nyland et al. [2] have recently shown that the covalent attachment of dansylamide to siloxane nanoparticles (NPs) enables the visualization of NPs and their immune active properties within cells. Dansylamide interacts with primary amino groups of ali- phatic and aromatic amines, forming stable fluorescent deriv- atives [3]. The diversity of the practical applications of dansylamide is primarily substantiated by the unique properties of this mole- cule due to the presence of two substituent groups, which are evidently different in nature and, thus, in their distinct elec- tronic interactions with the body of the molecule on one hand and with external functional groups and surfaces on the other. Dansylamide is also used as precursors for the synthesis of biologically active compounds, for plants protection, in syn- theses of intermediate products and dyes, and some other im- portant derivatives of naphthalene sulfonyl acids (anilides, esters, sulfones, etc.). Knowledge of structure and conforma- tional properties of such versatile compounds could be helpful to better understand their structure-activity relationship and, Electronic supplementary material The online version of this article (https://doi.org/10.1007/s11224-018-1108-2) contains supplementary material, which is available to authorized users. * Marwan Dakkouri marwan.dakkouri@uni–ulm.de 1 Department of Electrochemistry, University of Ulm, Ulm, Germany 2 Ivanovo State University of Chemistry and Technology, Ivanovo, Russia 3 Ivanovo State University, Ivanovo, Russia Structural Chemistry https://doi.org/10.1007/s11224-018-1108-2