Picolinic and Isonicotinic Acids: a Fourier Transform Microwave Spectroscopy Study

Subscriber access provided by UNIV OF CALIFORNIA SAN DIEGO LIBRARIES Article Picolinic and Isonicotinic Acids: a Fourier Transform Microwave Spectroscopy Study Isabel Peña, Marcelino Varela, Vanina Franco, Juan Carlos Lopez, Carlos Cabezas, and Jose Luis Alonso J. Phys. Chem. A, Just Accepted Manuscript • DOI: 10.1021/jp509823v • Publication Date (Web): 10 Nov 2014 Downloaded from http://pubs.acs.org on November 17, 2014 Just Accepted “Just Accepted” manuscripts have been peer-reviewed and accepted for publication. They are posted online prior to technical editing, formatting for publication and author proofing. The American Chemical Society provides “Just Accepted” as a free service to the research community to expedite the dissemination of scientific material as soon as possible after acceptance. “Just Accepted” manuscripts appear in full in PDF format accompanied by an HTML abstract. “Just Accepted” manuscripts have been fully peer reviewed, but should not be considered the official version of record. They are accessible to all readers and citable by the Digital Object Identifier (DOI®). “Just Accepted” is an optional service offered to authors. Therefore, the “Just Accepted” Web site may not include all articles that will be published in the journal. After a manuscript is technically edited and formatted, it will be removed from the “Just Accepted” Web site and published as an ASAP article. Note that technical editing may introduce minor changes to the manuscript text and/or graphics which could affect content, and all legal disclaimers and ethical guidelines that apply to the journal pertain. ACS cannot be held responsible for errors or consequences arising from the use of information contained in these “Just Accepted” manuscripts. The Journal of Physical Chemistry A is published by the American Chemical Society. 1155 Sixteenth Street N.W., Washington, DC 20036 Published by American Chemical Society. Copyright © American Chemical Society. However, no copyright claim is made to original U.S. Government works, or works produced by employees of any Commonwealth realm Crown government in the course of their duties. Page 1 of 24 The Journal of Physical Chemistry 1 2 3 4 5 6 7 8 Picolinic and Isonicotinic Acids: a Fourier 9 10 11 12 Transform Microwave Spectroscopy Study 13 14 15 16 17 Isabel Peña, Marcelino Varela, Vanina G. Franco, Juan C. López, Carlos Cabezas and José L. 18 19 Alonso* a 20 21 22 aGrupo de Espectroscopia Molecular (GEM). Edificio Quifima. Laboratorios de Espectroscopia 23 24 25 y Bioespectroscopia. Unidad Asociada CSIC. Universidad de Valladolid, 47011 Valladolid, 26 27 Spain 28 29 30 31 KEYWORDS Conformational analysis; Laser ablation; Hydrogen bonding; Mesomeric effect; 32 33 Molecular structure 34 35 36 37 ABSTRACT The rotational spectra of laser ablated picolinic and isonicotinic acids have been 38 39 studied using broadband chirped pulse (CP-FTMW) and narrowband molecular beam (MB- 40 41 42 FTMW) Fourier transform microwave spectroscopies. Two conformers of picolinic acid, s-cis-I 43 44 and s-cis-II, and one conformer of isonicotinic acid have been identified through the analysis of 45 46 their rotational spectra. The values of the inertial defect and the quadrupole coupling constants 47 48 49 obtained for the most stable s-cis-I conformer of picolinic acid, evidence the formation of an O- 50 51 H···N hydrogen bond between the acid group and the endocyclic N atom. The stabilization 52 53 provided by this hydrogen bond compensates the destabilization energy due to the adoption of a - 54 55 56 COOH trans configuration in this conformer. Its rs structure has been derived from the rotational 57 58 59 60 ACS Paragon Plus Environment 1 The Journal of Physical Chemistry Page 2 of 24 1 2 3 spectra of several 13 C, 15 N and 18 O species observed in their natural abundances. Mesomeric 4 5 14 6 effects have been revealed by comparing the experimental values of the N nuclear quadrupole 7 8 coupling constants in the isomeric series of picolinic, isonicotinic and nicotinic acids. 9 10 11 12 INTRODUCTION 13 14 The two isomeric molecules picolinic (pyridine-2-carboxylic acid) and isonicotinic (pyridine- 15 16 17 4-carboxylic acid) acids (C 6H5NO 2) are pyridine derivatives which have a great interest due to 18 19 their chemical and biological properties. The isonicotinic acid is a main metabolite of 20 21 1 22 isonicotinic acid hydrazide which is used as a therapeutic drug for tuberculosis. The picolinic 23 24 acid is an endogenous metabolite of L-tryptophan which has been detected in several biological 25 26 mediums as blood serum, cerebrospinal fluid, human milk, pancreatic juice and intestinal 27 28 2-5 29 homogenates. Picolinic acid is also known as a metal chelating agent in the human body. They 30 31 have been investigated in condensed phases using IR, Raman and X-ray techniques 6-13 but none 32 33 of them provide a detailed conformational picture about these isomeric species. Hence, the 34 35 36 experimental and theoretical vibrational spectra have been interpreted in terms of the 37 38 wavenumbers and intensities of selected experimental bands,11 which have been compared and 39 40 discussed on the basis of the position of the nitrogen atom in the aromatic ring. All results 41 42 43 indicate that the structural propensities observed in condensed phases are strongly biased by 44 45 interactions with the solvent or the crystal packing forces.12,13 46 47 48 The unambiguous characterization of the intrinsic conformational preferences can be achieved 49 50 through the analysis of the rotational spectra. Molecules placed in an isolated environment such 51 52 as that provided by the gas phase, free of the interactions with the solvent, exhibit their intrinsic 53 54 55 molecular properties. In the present work we have investigated the rotational spectra of the 56 57 biological active molecules picolinic and isonicotic acids to obtain precise information on their 58 59 60 ACS Paragon Plus Environment 2 Page 3 of 24 The Journal of Physical Chemistry 1 2 3 conformation and structure. The combination of narrowband molecular beam Fourier transform 4 5 6 microwave (MB-FTMW) spectroscopy and broadband chirped pulse Fourier transform (CP- 7 8 FTMW) with laser ablation (LA) vaporization provides a powerful experimental tool 14,15 which 9 10 11 allows the investigation of the rotational spectra of solid biomolecules such as natural amino 12 16 17 18 19 13 acids, dipeptides, nucleic acid bases, and monosacharides in the gas phase. We present 14 15 here the first experimental rotational studies of picolinic and isonicotinic acids using a 16 17 18 combination of the aforementioned techniques. The results have been compared with those 19 20 previously reported for nicotinic acid (pyridine-3-carboxylic acid), in which two conformers, s- 21 22 cis and s-trans have been recently unveiled.14 23 24 25 26 27 EXPERIMENTAL SECTION 28 29 Details of the Chirped-pulse Fourier transform microwave (CP-FTMW) spectrometer coupled 30 31 14 32 with a laser ablation source are given elsewhere. Cylindrical rods of picolinic acid (m.p.: 138 33 34 ºC) and isonicotinic acid (m.p.: 310 ºC) samples were obtained by pressing a mixture formed by 35 36 37 fine powder of the substances with a few drops of a commercial binder, in a hydraulic bench 38 14 39 press. They were vaporized in the ablation nozzle of the spectrometer using the third harmonic 40 41 (355nm) of a ps Nd:YAG laser (Ekspla, 20ps 15mJ/pulse). The vaporized molecules seeded in 42 43 44 the carrier gas Ne (stagnation pressure of 10 bar) were expanded supersonically into the vacuum 45 46 chamber and probed by a microwave chirped pulse. Up to 60 000 individual free induction 47 48 decays (4 FIDs on each valve cycle) for picolinic and isonicotinic acids were averaged in the 49 50 51 time domain and Fourier transformed to obtain the frequency domain rotational spectra from 6 to 52 53 10.2 GHz shown in Figures 1 and 2. A Kaiser-Bessel window was applied to increase the 54 55 baseline resolution. 56 57 58 59 60 ACS Paragon Plus Environment 3 The Journal of Physical Chemistry Page 4 of 24 1 2 3 Additional measurements were done using the higher resolution of our LA-MB-FTMW 4 5 15 14 6 spectrometer to resolve the N nuclear quadrupole coupling hyperfine structure. This 7 8 spectrometer which works in the 4-12 GHz frequency region uses a laser ablation system with a 9 10 11 ps-laser (Quantel, 35ps 12mJ/pulse). The vaporized molecules were seeded in Ne at 15 bar of 12 13 pressure and introduced into a Fabry-Pérot resonator to form a supersonic jet. A short microwave 14 15 radiation pulse (0.3µs) was then applied to macroscopically polarize the molecules in the beam. 16 17 18 The subsequent molecular emission signal was collected and Fourier transformed to obtain the 19 20 spectrum in the frequency domain. In our setup, the microwave radiation travels parallel to the 21 22 23 axis of the resonator, and consequently, all transitions appear as doublets because of the Doppler 24 25 effect (see inlets of Figure 1). The line width in this experiment is of ca. 5 kHz and the accuracy 26 27 of the frequency measurements is better than 3 kHz. 28 29 30 31 32 RESULTS AND DISCUSSION 33 34 Rotational spectra analysis 35 36 37 According to simple considerations based on the expected coplanarity of the acid and pyridine 38 39 moieties, two possible arrangements s-cis or s-trans of the –COOH group relative to the N atom 40 41 can be anticipated for picolinic acid.

Load more