Rotational Spectrum of Saccharin: Structure and Sweetness - The

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A: Spectroscopy, Molecular Structure, and Quantum Chemistry

The Rotational Spectrum of Saccharin: Structure and Sweetness Elena R. Alonso, Iker León, Lucie Kolesnikova, and Jose Luis Alonso J. Phys. Chem. A, Just Accepted Manuscript • DOI: 10.1021/acs.jpca.8b12211 • Publication Date (Web): 07 Mar 2019 Downloaded from http://pubs.acs.org on March 10, 2019

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The Journal of Physical Chemistry

The Rotational Spectrum of Saccharin: Structure and Sweetness

Elena R. Alonsoa, Iker Leóna, Lucie Kolesnikováa, and Jose L. Alonsoa. aGrupo

de Espectroscopía Molecular (GEM), Edificio Quifima, Laboratorios de

Espectroscopia y Bioespectroscopia, Unidad Asociada CSIC, Parque Científico UVa, Universidad de Valladolid, 47011 Valladolid, Spain

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The Journal of Physical Chemistry 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

ABSTRACT We present the first high-resolution rotational study of the artificial sweetener saccharin. By combining laser ablation (LA), narrow- and broadband Fourier transform microwave techniques (FTMW) and supersonic expansions, we have transferred the solid of saccharin (m.p. 229 ºC) to a supersonic jet and captured its rotational spectrum. The rotational constants were accurately determined by fitting more than 60 rotational transitions for the parent and 34S isotopic species in the 6.4–10.4 GHz frequency range. Experiment and complementary quantum-chemical calculations provide accurate geometrical parameters for saccharin, the first artificial sweetener investigated by highresolution microwave spectroscopy. The detailed structural information extracted from the rotational and 14N nuclear quadrupole coupling constants provided useful data in the context of the old theories of sweetness.


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INTRODUCTION The food industry has in part evolved following health demands. E.g., with obesity being one of the more widespread problems, natural sugars have largely been replaced by artificial sweeteners with the aim of offering the consumer the sweet taste without the physiological energy intake, since they are not metabolized. Saccharin (1,1-dioxo-1,2benzothiazol-3-one, Scheme 1) is a white crystalline substance considered to be about 300 times sweeter than sucrose. It was accidentally discovered in 1879 by Constantine Fahlberg in the course of the study of products derived from coal tar.1 After unintentionally spilling a solution of the product on his hand, Fahlberg inadvertently perceived a sweet taste in the food he had touched. Since its discovery, saccharin is used in a wide range of low-calorie and sugar-free foods and beverages.

In an attempt to rationalize the sweet taste, Shallenberger and Acree proposed in 1967 the molecular theory of sweet taste2 establishing a connection between the sweet taste and the structure of the molecules. They proposed that all sweet compounds have a common structural pattern called glucophore. It consists in two contact points, a proton donor (AH) and a proton acceptor (B), in a correct spatial disposition in such a way that the distance between them ranges from 2.5 Å to 4 Å. The significant observation that many D-amino acids are sweet while their L-isomers are not, led Kier to suggest a stereo-selective receptor site with three contact points. In his contribution to the model, there is a third hydrophobic γ-site in the molecule capable of enhancing the sweet flavour interacting via hydrophobic interaction with the receptor, forming what is currently known as the “sweetness triangle”.3–5 The sweet response is produced via the interaction with a complementary tripartite AH-B-γ site in the taste bud receptor.6 Although this theory seems simple, it is considered a unifying criterion to understand the structure-sweetness ACS Paragon Plus Environment


relationship. Indeed, recently this was proven in the family of ketohexoses.7 Regarding saccharin, many investigators agree on the glucophore assignment, suggesting that the imine group acts as a proton donor (AH) and the sulphoxide as the proton acceptor (B).2,3,8,9 Substitution at any of these positions on saccharin comes with a complete lost of its sweetness, supporting the molecular theory of sweet taste.10 Crystalline saccharin has been studied by X-ray diffraction.11 However, the structure of saccharin in its crystal form could be affected by lattice constraints, which can make it difficult to conclude about the structure-sweetness connection. Gas phase studies, on the other hand, provide the necessary isolation to obtain information on intrinsic properties directly related to the unperturbed structure. Nowadays, the availability of advanced experimental techniques12 and their application to solid compounds have allowed the elucidation of the individual conformations of glucose,13 galactose,14 fructose15 and ketohexoses7 in isolated conditions of the gas-phase. Three-dimensional representations of the contact surface of the sugars have extended the visual perception of sweeteners. Incorporation of such results into structure-sweetness consideration, led to a new allocation of the Shallenberger-Acree-Kier tripartite AH, B, γ glucophore in several sweet substances.7 In this context, it is of interest to extend the structural studies to a representative non-carbohydrate sweetener as saccharin.

Scheme 1. Scheme of the chemical structure of saccharin showing the tripartite AH, B, γ proposed by Kier.


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Saccharin (m.p. 229 ºC) is a thermally fragile molecule and cannot be transferred intact into the vapor phase by using conventional heating methods. So far, no rotational studies have been reported due to the challenges in vaporization. To bring saccharin into the gasphase, and to obtain the rotational spectrum, we have used a laser ablation source coupled with high-resolution Fourier transform microwave techniques. In a first stage of the investigation, a chirped pulse Fourier transform microwave spectrometer16 in combination with a picosecond laser ablation technique in a supersonic expansion (LACP-FTMW)17,18 was used to provide the first rotational signatures of saccharin.

METHODS Experimental details Solid samples of saccharin were ground and mixed with a minimum amount of a commercial binder and pressed into cylindrical rods, which were placed in an ablation nozzle and vaporized using an Nd:YAG picosecond laser. Then, saccharin molecules were seeded in the carrier gas Ne at a backing pressure of 10 bar, to expand adiabatically into the vacuum chamber. An arbitrary waveform generator created a chirped pulse from 6.4 to 10.4 GHz, which was directly amplified by a 300 W traveling wave tube amplifier. The conventional microwave horns have been replaced by the parabolic reflector system composed by dual ridge horns, and two parabolic reflectors (40 cm diameter) separated 70 cm in a paraxial beam configuration.18 The excitation pulse emerged from a horn antenna to polarize the molecules arising from the laser ablation nozzle located at the center of one of the parabolic reflectors. A second ridge horn antenna was used to detect the free induction decay signal (FID), which was finally amplified and digitized on a fast oscilloscope. This technique makes possible to record a full range of frequencies spectra



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in a single acquisition by employing polarization pulses consisting of short and intense microwave chirps in broadband excitation schemes.16 The molecules present in the supersonic jet are rotationally cooled to temperatures below 4K, populating the lower energy levels and increasing the intensity of the transitions originating from these levels. The size of molecular systems like saccharin implies that the strongest rotational lines are situated at the lower side of the microwave frequency region. The Laser Ablation Molecular Beam Fourier Transform Microwave (LA-MB-FTMW) spectrometer19 was used to record the saccharin spectrum with the necessary resolution to analyze the hyperfine structure due to the presence of a

14N

nucleus. The optimal

conditions to polarize the molecules in the jet correspond to molecular pulses of about 1.1 ms, followed by MW polarization pulses of 0.3 ms duration with powers of 1–40 mW. The microwave FID was recorded for 100 µs in the time domain at 40–100 ns sample intervals, and Fourier-transformed to the frequency domain. Due to the collinear disposition between the supersonic jet and the microwave resonator axis, all emission signals appeared to be split into Doppler doublets (Figure 2). The arithmetic mean of the doublets was taken as the rest frequency. The estimated accuracy of the frequency measurements is greater than 3 kHz. From 50 to 250 averages were phase-coherently coadded to achieve a reasonable signal-to-noise ratio. Theoretical Molecular geometry optimizations are used to predict molecular equilibrium properties from the potential energy surface. The resulting information on rotational constants, dipole moment components and quadrupole coupling constants are used to predict the rotational spectra and are essential for the spectral assignments. Both ab initio and density functional theory (DFT) methods are used to assist the assignment of the rotational spectrum. ACS Paragon Plus Environment

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The structure of saccharin was predicted by using the Gaussian suite of programs.20 Several computational methods with different basis were run in order to see which is the closest to our experimental data (see Table S1 of Supplementary Information). The model of choices were the B3LYP density functional21,22 including the Grimme D3 dispersion interactions23 with Becke-Johnson damping24 and the Minnesota hybrid meta exchangecorrelation functionals of the M06 suite (M06 and M06-2X),25 which are two representative DFT methods, and the second order perturbation theory Møller-Plesset (MP2).26 Two basis sets were tested, the Pople split-valence triple-zeta basis set augmented with diffuse and polarization functions on all atoms (the 6-311++G (d,p) basis set)27 and the augmented correlation-consistent polarized valence triple zeta basis set (the aug-cc-pVTZ basis set).28,29 The predicted rotational constants (A, B and C), quadrupole coupling constants (χaa, χbb and χcc) and electric dipole moment components of some selected methods are collected in Table 1. The values obtained for other theoretical models and basis sets can be found in the Supplementary Information for a comparison. RESULTS AND DISCUSSION The broadband microwave spectrum between 6.4 and 10.4 GHz is shown in Figure 1. On a first inspection, the lines of known photofragment species were identified and removed. In the lower insets of this Figure, we show segments of the spectrum, highlighting a progression of pairs of intense a-type R-branch transitions (J+1)1,J+1 ← J1,J ,(J+1)0,J+1 ← J0,J together with a weaker pair of b-type R-branch transitions (J+1)0,J+1 ← J1,J and (J+1)1,J+1 ← J0,J at each side of the intense a-type branch. Following the progression of these a/b-type quartets over the range J=5 to J=7, we observe a narrowing between transitions, resulting in coalescence for J=7 (lower inset in Fig.2) A primary set of rotational constants (A: 1299 MHz, B: 871 MHz, C: 580 MHz) was determined through a recurrent fit using a rigid rotor analysis. On this basis, new predictions and observations ACS Paragon Plus Environment


allowed the assignment of other a- and b-type R-branch lines confirming rotational assignments. A summary of the previous rotational parameters along with the fitted rotational transitions is provided in the Supporting information (Table S2).

Figure 1. Broadband rotational spectrum of saccharin from 6.4 to 10.4 GHz (more than 100.000 averages). Rotational transitions JK-1,K+1 denoted by the rotational quantum numbers J, K-1, and K+1, with J being the rotational angular momentum quantum number and K-1 and K1 being the projections of J onto the principal axes at the prolate and oblate symmetric top limits, respectively. The lower insets show segments of the spectrum with the assigned quartets (see text). All the transitions corresponding to saccharin are identified together with other lines due to photofragmentation.


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An inconvenience when analyzing the rotational spectrum of saccharin was the nuclear quadrupole coupling interactions produced by the quadrupole nucleus 14N that split each rotational level into several sublevels.30 Consequently, the overall intensity of each rotational transition spreads over several hyperfine components that appeared not-well resolved with the available resolution of our broadband LA-CP-FTMW technique. Only singular transitions as those of (J+1)2,J+1 ← J0,J of J=2 and J=3 transitions, shown in the upper inset of Fig. 1, appeared well resolved. At that point, we took advantage of the higher resolution of our narrowband LA-MB-FTMW.31 It provides the sub-Doppler resolution necessary to undertake the analysis of the

14N

hyperfine structure of the

rotational transitions. This is exemplified for the 76 quartets of rotational transitions in Figure 2. A total of 60 hyperfine components belonging to 12 a-type and 8 b-type Rbranch transitions was measured in the range from 6.4-10.4 GHz. They were fitted32 using a rigid rotor Hamiltonian HR(A) supplemented with an HQ term to account for the nuclear quadrupole coupling.30 The Hamiltonian was set up in the coupled basis set I + J = F and diagonalized in blocks of F. The experimentally determined rotational constants A, B, C, and the nuclear quadrupole coupling constants χaa, χbb, and χcc for the observed species are given in Table 1. All measured transitions are collected in Table S3 of Supplementary Information. Also, a semi-rigid rotor fit including the centrifugal distortion constants predicted at M06-2X/aug-cc-pVTZ was made (see Table S4 of the Supplementary Information) to show how their inclusion affect the rotational constants and deviation of the fit. The low value of the predicted centrifugal distortion constants serves as an indicator of structure rigidity, nevertheless, the best fit is reached using a rigid rotor analysis.



Figure 2. The J= 7-6 quartet of saccharin showing the 14N quadrupole hyperfine structure for each a- and b- type R-branch transition entirely resolved by using the LA-MB-FTMW spectrometer. Since the molecular beam and the microwave radiation propagate coaxially, each rotational transition appears as a doublet due to the Doppler effect.

In Table 1, we compare the experimentally determined parameters with theoretical calculations obtained at different levels of theory. We found a remarkably good agreement between the experimental and calculated rotational constants and the values of the nuclear quadrupole coupling constants. In addition, the magnitudes of the permanent dipole moment components are in accordance with the observed selection rules and intensities. The exceptional matching between experimental rotational constants and those predicted from the equilibrium structure at the M06-2X/aug-cc-pVTZ level of theory (relative errors less than 0.2 %) allows for the assumption that the actual structure of saccharin closely matches the one theoretically predicted (see the Supporting


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Information for further details); one has to be aware, however, that a zero-point vibrational energy averaged r0 structure is compared to a re structure, respectively. Table 1. Experimental spectroscopic constants of saccharin compared to those predicted theoretically. Parent

34S

MP2/

B3LYP-GD3BJ/

B3LYP-GD3BJ /

M062X/

M062X/

6-311++(d,p)

6-311++(d,p)

aug-cc-pVTZ

6-311++(d,p)

aug-cc-pVTZ

Aa

1298.4982(44)

1296.907(29)

1279.9

1279.8

1289.3

1293.2

1300.1

B

871.2573(29)

865.282(18)

861.4

858.0

863.6

865.5

870.6

C

579.46230(20)

576.41970(94)

573.8

572.3

575.9

577.2

580.4

χaab

1.84(17)

-

1.8

1.9

1.9

1.9

1.8

χbb

2.502(82)

-

2.7

3.1

2.8

3.0

2.7

χcc

-4.340(82)

-

-4.5

-5.0

-4.7

-4.9

-4.5

intense/weak/-

intense/weak/-

4.1/1.0/0.1

4.2/1.1/0.0

3.9/1.1/0.0

4.3/1.0/0.0

4.1/1.0/0.0

d

3.7

40.1

Pce

-97.1081(35)

-96.987(21)

-100.7

-100.9

-99.6

-99.1

-98.2

μa / μb / μcc

a

A, B, and C represent the rotational constants (in MHz); b χaa, χbb and χcc are the diagonal

elements of the 14N nuclear quadrupole coupling tensor (in MHz); c μa, μb and μc are the electric dipole moment components (in D); e rms deviation of the fit (in kHz). dPc is the planar inertial moment (in uÅ2), conversion factor: 505379.1 MHz-uÅ2.

An important structural information on the planarity of the saccharin skeleton that could have important implications on its properties as artificial sweetener can be extracted from the value of the planar inertial moment Pc = (Ia + Ib - Ic)/2 = ∑i mi ci2 where mi and ci are the mass and c coordinate of atom i, respectively. It gives the mass extension out of the



ab inertial plane. The experimental Pc value of -97.044 uA2 in Table 1 corresponds to the magnitude expected for a species with the two oxygen atoms of the sulfoxide group out of the plane. This is reasonably consistent with the theoretical calculations that predict planar or nearly planar framework configurations with Pc values ranging from -98.2 to 100.9 uA2 (see Table 1). However, there is no conclusive experimental evidence for planarity; small contributions from out-of-plane heavy atom skeleton vibrations cannot be initially discarded. A procedure to establish planarity is based on the determination of the inertial planar moment of a monosubstituted isotopologue. If, e.g., the sulfur atom is located in the ab symmetry plane, then the Pc values of the parent and 34S isotopic species must not significantly differ. Since the -NH should have the H pointing out of the plane, there could be a small tilt of the inertia ab-plane away from the heavy atom plane. Therefore, a definitive proof for a planar heavy atom skeleton is difficult to achieve. On this basis, taking advantage of the high sensitivity reached in the broadband chirped pulse experiment, a dedicated search was carried out to assign the rotational spectrum of the 34S isotopologue in its natural abundance (4%). Hence, in a detailed inspection of the spectrum, weak satellite lines were found at the low-frequency side of each intense pair (J+1)1,J+1 ← J1,J and (J+1)0,J+1 ← J0,J of a-type R-branch transitions of the parent species (see Figure 3). They were ascribed to the 34S monosubstituted isotopologue. A total of 14 transitions were measured (see Table S5 of Supplementary Information) and fitted to a rigid rotor Hamiltonian to give the set of rotational constants collected in Table 1. The very close values of Pc determined in Table 1 for the parent and the 34S isotopic species indicate that the substituted atom lies in the ab inertial plane and thus, the ab plane is a plane of symmetry in saccharin. The sulfoxide oxygens are out of the plane in equivalent positions.


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Figure 3. Fragment of the rotational spectrum of saccharin showing the quadruplet of strong pairs of a-type R-branch transitions (J+1)1,J+1 ←J1,J and (J+1)0,J+1 ←J0,J with J=6 and the two weaker btype R-branch transitions (J+1)0,J+1 ←J1,J and (J+1)1,J+1 ←J0,J. The satellites lines corresponding to (J+1)1,J+1←J1,J and (J+1)0,J+1←J0,J with J=6 transitions of the monosubstituted isotopologue of 34S are shown.

The AH, B, γ tripartite concept for sweetness has been not only applied to sugars but also as the unifying criterion applied to other sweeteners with different functional groups as saccharin. It is believed that the NH group acts as a proton donor (AH), the oxygens of the sulfoxide group as a proton acceptor (B), and the upper carbon of the benzene as the hydrophobic point γ (see Figure 4). The A-B distance calculated from the structure is 2.56 Å, and falls within the range proposed by Shallenberger and Acree.2 Due to the symmetry plane that makes both oxygens equivalent symmetrically, it can be said that saccharin has the same top and a bottom faces (see Figure 4).



A stereo-selective AH-B-gamma receptor site should distinguish between the two faces of saccharine: The top and bottom faces are mirror images like the inner surfaces of the left hand and a right hand, i.e. the tripartite AH-B-gamma has circular left-sense and circular right-sense, respectively. Therefore, despite the planarity of saccharine, only one side will interact with the receptor proposed by Kier.

Figure 4. The structure of saccharin highlighting the same top and a bottom faces with tripartite AH, B, γ glucophore anchor points.

CONCLUSION Laser ablation Fourier transform microwave spectroscopy techniques under the isolation conditions of a supersonic expansion provide a precise tool in the structural analysis. The accurate three-dimensional shapes resulting from rotational studies provide a more realistic structural description of the sweet molecules. Presently, we explore the promising capabilities of our current techniques in the study of larger artificial sweeteners.


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SUPPORTING INFORMATION DESCRIPTION Table S1. Theoretical calculations of the saccharin structure with different computational methods in comparison with the experimental rotational constants obtained. Table S2. Observed frequencies centres and residuals (in MHz) for the rotational transitions of conformer of saccharin (LA-CP-FTMW spectrometer). Table S3. Observed frequencies and residuals (in MHz) for the rotational transitions of conformer of saccharin (LA-MB-FTMW spectrometer). Table S4. Fit with and without the inclusion of the centrifugal distortion constants calculated at M06-2X/aug-cc-pVTZ for saccharin. Table S5. Observed frequencies centres and residuals (in MHz) for the rotational transitions of

34S

monosubstituted isotopologue of saccharin (LA-CP-FTMW

spectrometer). Table S6. Cartesian coordinates for saccharin. The geometries have been optimized ab initio at the M062X/aug-cc-pTVZ level of theory. Table S7. Structure parameters for saccharin obtained at the M062X/aug-cc-pTVZ level of theory.

ACKNOWLEDGEMENTS The financial fundings from Ministerio de Ciencia e Innovación (ConsoliderIngenio 2010 CSD2009-00038 program "ASTROMOL", CTQ2013-40717-P and CTQ2016-76393-P), Junta de Castilla y León (Grants VA175U13 and VA077U16) and European Research Council under the European Union's Seventh Framework Programme (FP/2007-2013) / ERC-2013-SyG, Grant Agreement n.



610256 NANOCOSMOS, are gratefully acknowledged. E.R.A. thanks Ministerio de Ciencia e Innovación for FPI grant (BES-2014-067776) and I.L.O. thanks Universidad de Valladolid for a postdoctoral contract.

REFERENCES

(1)

Fahlberg, C. Saccharin Compound. 326,281, 1885.

(2)

Shallenberger, R. S.; Acree, T. E. Molecular Theory of Sweet Taste. Nature 1967, 216, 480.

(3)

Kier, L. B. A Molecular Theory of Sweet Taste. J. Pharm. Sci. 1972, 61 (9), 1394–1397.

(4)

van der Heijden, A.; Brussel, L. B. P.; Peer, H. G. Chemoreception of SweetTasting Dipeptide Esters: A Third Binding Site. Food Chem. 1978, 3 (3), 207– 211.

(5)

Yamazaki, T.; Benedetti, E.; Kent, D.; Goodman, M. Conformational Requirements for Sweet-Tasting Peptides and Peptidomimetics. Angew. Chemie Int. Ed. 1994, 33 (14), 1437–1451.

(6)

Lee, C. K. The Chemistry and Biochemistry of the Sweetness of Sugars. Adv. Carbohydr. Chem. Biochem. 1987, 45 (C), 199–351.

(7)

Bermúdez, C.; Peña, I.; Mata, S.; Alonso, J. L. Inside Back Cover: Sweet Structural Signatures Unveiled in Ketohexoses (Chem. Eur. J. 47/2016). Chem. A Eur. J. 2016, 22 (47), 17047–17047.


Page 16 of 20

Page 17 of 20 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


(8)

Beets, M. G. J. Structure-Activity Relationships in Human Chemoreception; Elsevier Applied Science: London, 1978.

(9)

Heijden, A. van der; Wel, H. van der; Peer, H. G. Structure-Activity Relationships in Sweeteners. II. Saccharins, Acesulfames, Chlorosugars, Tryptophans and Ureas. Chem. Senses 1985, 10 (1), 73–88.

(10)

Shallenberger, R. S. Taste Chemistry; Springer US, 2012.

(11)

Okaya, Y. The Crystal Structure of Saccharin o -Sulfobenzoimide, C 6 H 4 CO.NH.SO 2 , an Artificial Sweetening. Acta Crystallogr. Sect. B Struct. Crystallogr. Cryst. Chem. 1969, 25 (11), 2257–2263.

(12)

Alonso, J. L.; López, J. C. Microwave Spectroscopy of Biomolecular Building Blocks. Top. Curr. Chem. 2014, 364, 335.

(13)

Alonso, J. L.; Lozoya, M. A.; Peña, I.; López, J. C.; Cabezas, C.; Mata, S.; Blanco, S.; Pen; Lo; Cabezas, C.; et al. The Conformational Behaviour of Free D-Glucose-at Last. Chem. Sci. 2014, 5, 515.

(14)

Peña, I.; Cabezas, C.; Alonso, J. L. Unveiling Epimerization Effects: A Rotational Study of α-d-Galactose. Chem. Commun. 2015, 51, 10115.

(15)

Bermúdez, C.; Peña, I.; Cabezas, C.; Daly, A. M.; Alonso, J. L. Unveiling the Sweet Conformations of D-Fructopyranose. ChemPhysChem 2013, 14, 893.

(16)

Brown, G. G.; Dian, B. C.; Douglass, K. O.; Geyer, S. M.; Shipman, S. T.; Pate, B. H. A Broadband Fourier Transform Microwave Spectrometer Based on



Chirped Pulse Excitation. Rev. Sci. Instrum. 2008, 79, 53103.

(17)

Mata, S.; Pena, I.; Cabezas, C.; López, J. C.; Alonso, J. L. A Broadband FourierTransform Microwave Spectrometer with Laser Ablation Source: The Rotational Spectrum of Nicotinic Acid. J. Mol. Spectrosc. 2012, 280 (0), 91–96.

(18)

Peña, I.; Mata, S.; Martín, A.; Cabezas, C.; Daly, A. M.; Alonso, J. L. Conformations of D-Xylose: The Pivotal Role of the Intramolecular HydrogenBonding. Phys. Chem. Chem. Phys. 2013, 15, 18243.

(19)

Alonso, J. L.; Pérez, C.; Eugenia Sanz, M.; López, J. C.; Blanco, S.; Sanz, M. E.; López, J. C.; Blanco, S. Seven Conformers of L-Threonine in the Gas Phase: A LA-MB-FTMW Study. Phys. Chem. Chem. Phys. 2009, 11 (4), 617–627.

(20)

Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb, M. A.; Cheeseman, J. R.; Scalmani, G.; Barone, V.; Mennucci, B.; Petersson, G. A.; et al. Gaussian 09, Revision D.01. Gaussian 09, Revision D.01, Gaussian, Inc., Wallingford CT. 2009.

(21)

Becke, A. D. A New Mixing of Hartree-Fock and Local Density-Functional Theories. J. Chem. Phys. 1993, 98 (2), 1372–1377.

(22)

Becke, A. D. Densityfunctional Thermochemistry. I. The Effect of the Exchange Only Gradient Correction. J. Chem. Phys. 1992, 96 (3), 2155–2160.

(23)

Grimme, S.; Antony, J.; Ehrlich, S.; Krieg, H. A Consistent and Accurate Ab Initio Parametrization of Density Functional Dispersion Correction (DFT-D) for


Page 18 of 20

Page 19 of 20 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


the 94 Elements H-Pu. J. Chem. Phys. 2010, 132 (15), 154104.

(24)

Grimme, S.; Ehrlich, S.; Goerigk, L. Effect of the Damping Function in Dispersion Corrected Density Functional Theory. J. Comput. Chem. 2011, 32 (7), 1456–1465.

(25)

Zhao, Y.; Truhlar, D. G. The M06 Suite of Density Functionals for Main Group Thermochemistry, Thermochemical Kinetics, Noncovalent Interactions, Excited States, and Transition Elements: Two New Functionals and Systematic Testing of Four M06-Class Functionals and 12 Other Function. Theor. Chem. Acc. 2008, 120 (1–3), 215–241.

(26)

Møller, C.; Plesset, M. S. Note on an Approximation Treatment for ManyElectron Systems. Phys. Rev. 1934, 46 (7), 618–622.

(27)

Frisch, M. J.; Pople, J. A.; Binkley, J. S. Self-Consistent Molecular Orbital Methods 25. Supplementary Functions for Gaussian Basis Sets. J. Chem. Phys. 1984, 80 (7), 3265–3269.

(28)

Kendall, R. A.; Dunning, T. H.; Harrison, R. J. Electron Affinities of the FirstRow Atoms Revisited. Systematic Basis Sets and Wave Functions. J. Chem. Phys. 1992, 96 (9), 6796–6806.

(29)

Dunning, T. H. Gaussian Basis Sets for Use in Correlated Molecular Calculations. I. The Atoms Boron through Neon and Hydrogen. J. Chem. Phys. 1989, 90 (2), 1007–1023.



(30)

Gordy, W.; Cook, R. L. Microwave Molecular Spectra, 3rd ed.; Wiley, 1984.

(31)

Bermúdez, C.; Mata, S.; Cabezas, C.; Alonso, J. L. Tautomerism in Neutral Histidine. Angew. Chemie - Int. Ed. 2014, 53 (41), 11015–11018.

(32)

Pickett, H. M. The Fitting and Prediction of Vibration-Rotation Spectra with Spin Interactions. J. Mol. Spectrosc. 1991, 148 (2), 371–377.

TABLE OF CONTENTS

The artifical sweetener saccharin has been vaporized by laser ablation (LA) and probed in a supersonic expansion by broadband and narrowband Fourier transform microwave spectroscopy. The planarity of the framework unveiled in saccharin guarantees that it always interacts with a stereo-selective AH-B gamma receptor site in our tongue according with Shallenberger and Acree´s molecular theory of sweet taste. It could explain the sweeter taste that presents.


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Rotational Spectrum of Saccharin: Structure and Sweetness - The

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