On the structure of erythritol and L-threitol in the solid state: An infrared spectroscopic study

Journal of Molecular Structure 938 (2009) 156–164

Contents lists available at ScienceDirect

Journal of Molecular Structure journal homepage: www.elsevier.com/locate/molstruc

On the structure of erythritol and L-threitol in the solid state: An infrared spectroscopic study A.J. Lopes Jesus a,b,*, J.S. Redinha b a b

Faculty of Pharmacy, University of Coimbra, 3004-295 Coimbra, Portugal Department of Chemistry, University of Coimbra, 3004-535 Coimbra, Portugal

a r t i c l e

i n f o

Article history: Received 20 July 2009 Received in revised form 10 September 2009 Accepted 14 September 2009 Available online 18 September 2009 Keywords: Erythritol L-threitol Infrared spectroscopy Hydrogen bonding Correlation between structural and spectroscopic data Crystal conformation

a b s t r a c t FTIR spectra of crystalline erythritol and L-threitol were recorded between 4000 and 400 cm1, at temperatures ranging from 298 K to 15 K. The most important bands were assigned by comparing the experimental and theoretical spectra. The latter were obtained from optimizations that started with the original crystal coordinates taken from the X-ray and neutron diffraction data, using the B3LYP/6311++G(d, p) model chemistry. Spectra of the deuterated solids at 15 K were also used to help with the spectral assignments, particularly in the OH stretching region. The hydrogen bonding network of both isomers was the object of particular attention in the optimized conformations as well as in the crystalline solids. The possible existence of intramolecular hydrogen bonds in the optimized structures was checked by Atoms-In-Molecules (AIM) and Natural Bond Orbital (NBO) theories. A correlation between the spectroscopic results and the diffraction data was obtained. Ó 2009 Elsevier B.V. All rights reserved.

1. Introduction Alditols, also called sugar alcohols, are acyclic polyols having the general formula HOCH2[CH(OH)]nCH2OH. Because of their lower caloric value when compared to sucrose, without loss of the sweet taste of sugar, some of these compounds have been widely used in the food and pharmaceutical industries as sweeteners [1–3]. The four-carbon sugar alcohol (1,2,3,4-butanetetrol) exhibits two diastereomers: erythritol and threitol. The first is a meso form (often called meso-erythritol), while the second is optically active. In addition to their use as pharmaceutical ingredients, in particular erythritol [4,5], these simple polyols are also known to act as protein stabilizers [6,7] and cryoprotectant agents for plant and animal tissues [8]. It is well known that hydrogen bonding (H-bonding) plays a determinant role in most of the physical, chemical and biological properties of polyols [9,10]. However, the achievement of detailed structural information (either experimentally or theoretically) in large polyols is frequently limited owing to the complexity of inter or intramolecular H-bonds network. Thus, relatively small sized

* Corresponding author. Address: Faculty of Pharmacy, University of Coimbra, 3004-295 Coimbra, Portugal. E-mail address: [email protected] (A.J.L. Jesus). 0022-2860/$ - see front matter Ó 2009 Elsevier B.V. All rights reserved. doi:10.1016/j.molstruc.2009.09.018

polyols, such as erythritol and L-threitol, may be used as suitable compounds to obtain an insight into the most important structural features that determine the structure of polyols. In this work the structures of solid erythritol and L-threitol have been investigated by infrared spectroscopy. As H-bonding plays an important role in the intermolecular interactions, this is a powerful method to study the structure of these compounds. Furthermore, the comparison of these data with those provided by X-ray and neutron diffraction techniques allows us to obtain a more complete picture of their structure. In view of the importance of the isolated molecules as reference in the study of the condensed states of matter, a brief discussion on the main intramolecular interactions in the optimized crystal conformations has been made. Owing to the presence of four OH groups, particular attention was given to the identification and characterization of possible intramolecular hydrogen bonds involving these groups. This discussion was made on the basis of the geometric data, together with results of Natural Bond Orbitals (NBO) and Atoms-In-Molecules (AIM) analyses. Spectra of the solids were recorded from 4000 to 400 cm1 at temperatures ranging from room temperature down to 15 K. To help in the band assignments, reference spectra have been calculated for the optimized molecular conformations exhibited by the compounds in the crystal structure at the B3LYP/6-311++G(d, p) level of theory. In addition, experimental spectra of the

A.J. Lopes Jesus, J.S. Redinha / Journal of Molecular Structure 938 (2009) 156–164

partially-deuterated compounds have also been obtained to better identify bands associated with OH groups.

157

3. Results and discussion 3.1. Optimized molecular crystal conformations

2. Experimental 2.1. Materials Commercial erythritol and L-threitol, purchased from Fluka (x > 99%) and Aldrich (x = 99%), respectively, were used in the spectroscopic experiments. The solids were dried under vacuum at 353 K (erythritol) and 303 K (L-threitol) for a few days before using. Purity was checked by gas chromatography and elemental analysis (see Ref. [11] for details). Degrees of purity of 99.9% and 99.8% were found for erythritol and L-threitol, respectively. Deuterated compounds were obtained by dissolving the solids in methanol-d (Aldrich, 99.5 atom % d) under an argon atmosphere. The evaporation of the solvent was carried out at 60 °C under reduced pressure. Since both compounds are hygroscopic, in particular L-threitol, these were handled inside a glovebox under dry nitrogen atmosphere.

2.2. Infrared spectroscopy The infrared spectra of the samples dispersed in KBr were recorded within the 4000–400 cm1 frequency region using a Thermo Nicolet Nexus 670 FTIR spectrometer, equipped with deuterated triglycine sulfate (DTGS) detector and ‘‘solid substrate” (silicon) beamsplitter, with spectral resolution of 1 cm1. Spectra at low temperatures were recorded by attaching the KBr pellet to the cold finger of an APD cryogenics closed-cycle helium refrigeration system with a DE-202A expander. The temperature (298– 15 K) was measured directly at the sample holder by a silicon diode temperature sensor connected to a Scientific Instruments temperature controller (model 9650). The sample temperature during registration of spectra was stabilized to ca. 0.2 K. The temperature-induced spectral changes observed for all substances were found to be reversible and highly reproducible.

From neutron diffraction analysis, it has been found that the erythritol molecule adopts two conformations (A and B) in the crystal lattice that are illustrated in Fig. 1. These conformations differ from each other in the positions of the two middle hydrogen atoms, H(2) and H(3). Both structures present a Ci symmetry with the inversion center located at the middle of the C(2)–C(3) bond. The relative populations of A and B in the unit cell at 22.6 K are 85% and 15%, respectively [13]. Table 1 presents the values of the dihedral angles of the structures before and after optimization. From these data one can see that the B3LYP/6-311++G(d, p) optimization of conformation A does not significantly change its initial geometry. Only small variations in the bond angles and the terminal HAOACAC dihedrals are found. This optimized conformation corresponds to the fourth most abundant conformer in the gas phase conformational equilibrium [18]. Unlike conformation A, the optimized structure of conformation B is quite different from the original one. The terminal HAOACAC dihedrals change from ± gauche to trans (80 ? 176° or 80 ? 176°), while the middle HAO(2)AC(2)AC(1) or HAO(3)A C(3)AC(4) dihedrals change from 86° to 39° and from 86° to 39°. This structure represents the sixth most stable conformer in the gas phase [18]. Since the optimized geometry of conformation B is significantly different from that present in the crystal structure,

2.3. Computational calculations The molecular conformations existent in the crystal structure, obtained from the X-ray [12] and neutron diffraction data [13], were used as starting structures to calculate the theoretical spectra. These conformations were fully optimized at the B3LYP/6311++G(d, p) level of theory followed by harmonic frequencies calculations. The absence of imaginary frequencies confirmed that these structures are minima on the potential energy surface. The calculated frequencies were scaled using the following scale factors: 0.954 for the OH stretching vibrations, 0.963 for the CH stretching vibrations, and 0.978 for all the other vibrations. The calculated spectra were simulated using Lorentzian functions centered at the calculated (scaled) frequencies and with a half-height bandwidth equal to 2 cm1. An approximate description of the vibrational frequencies was performed by animation of the vibrational modes using the Gaussview 3.0 graphical interface. All calculations were performed with the Gaussian 03 program package [14]. Natural Bond Orbital (NBO) analysis has been performed at B3LYP/6-311++G(d, p) level with the NBO 5.0 program [15] linked to the Gamess program version 22-Feb-2006 (R5). AIM (Atoms-InMolecules) calculations were performed with the Extreme program [16] included in the Aimpac software package [17]. The B3LYP/6311++G(d, p) wavefunction was used in these calculations.

Fig. 1. B3LYP/6-311++G** optimized conformations of erythritol (Conformations A and B) and L-threitol in the crystal structure, including atom numbering scheme. In the case of erythritol the non-optimized structure of conformation B is also shown. The starting conformations were obtained from the atomic coordinates given in references [13] and [12], for erythritol and L-threitol, respectively.

158

A.J. Lopes Jesus, J.S. Redinha / Journal of Molecular Structure 938 (2009) 156–164

Table 1 Dihedral angles of the non-optimized and optimized (B3LYP/6-311++G**) molecular crystal conformations of erythritol and L-threitol.a

a

Dihedral angle

Erythritol

L-Threitol

Non-optimized

Optimized

Non-optimized

Optimized

O(1)AC(1)AC(2)AO(2) O(2)AC(2)AC(3)AO(3) O(3)AC(3)AC(4)AO(4) C(1)AC(2)AC(3)AC(4) HAO(1)AC(1)AC(2) HAO(2)AC(2)AC(1) HAO(3)AC(3)AC(4) HAO(4)AC(4)AC(3)

62.8 180.0 62.8 180.0 80.1 156.3/86.2 156.3/86.2 80.1

63.0 180.0 63.0 180.0 59.6/175.5 155.5/39.1 155.5/39.1 59.6/175.5

174.3/173.7/173.3 57.1/58.2/54.5 178.0/177.6/177.7 175.3/173.9/174.7 69.3/82.6/67.0 59.5/62.3/58.1 160.2/120.4/144.8 78.4/64.2/87.7

177.2 47.5 175.4 165.9 74.6 82.7 141.7 75.1

Values separated by forward slash refer to conformations A and B in the case of erythritol and to conformations I, II and III in the case of L-threitol.

particularly in the relative OH groups orientation, the calculated reference spectrum of erythritol to be compared with the experimental one was that of conformation A. Unless otherwise stated, only this conformation is considered for erythritol in the following discussion. In the case of L-threitol, the X-ray diffraction data reveal the existence of three crystallographically independent conformations in the unit cell (designated as I, II and III) [12]. There are only slight structural differences among them. As expected, upon optimization, the three conformations converged to a single minimum (see Fig. 1), whose geometry is close to that of the starting structures (Table 1). Unlike erythritol, the optimized geometry of L-threitol in the crystal structure is not one of the most significant conformers of the gas phase conformational space [18]. As can be seen in Fig. 1, the relative orientations of the OH groups in the optimized geometries of erythritol could possible result into two symmetry-related intramolecular H-bonds involving the terminal and the respective vicinal OH group, O(1)AH  O(2) and O(4)AH  O(3). Similarly, an intramolecular H-bond connecting the two middle OH groups, O(2)AH  O(3), could be possible in L-threitol. Table 2 contains the geometric parameters closely related to hydrogen bonding. For the two molecules, the distances between the hydrogen and the acceptor oxygen (O  H) are well within the limits reported for this type of interaction (<3.0–3.2 Å) [19]. With respect to the angle formed by the three atoms involved in the interaction, the value obtained for erythritol is below the conventional limit (>110°) [19], while for L-threitol it slightly exceeds this limit. Hence, based on geometry, no significant intramolecular H-bonding exists in erythritol and a weak one may be present in L-threitol. To confirm whether or not intramolecular hydrogen bonds exist in the optimized molecular crystal conformations of both compounds, we made use of two further theories: Natural Bond Orbital (NBO) and Atoms-In-Molecules (AIM). According to the NBO analysis, a hydrogen bond corresponds to a electron transference from the lone pair (LP) of the electron donor to the antibonding orbital of the acceptor group, LP(O) ? r* (OH) [20]. The stabilization energies corresponding to this orbital interaction, E(2), are included in Table 2. The value obtained for erythritol is negligible and a very low one was found for the intramolecular interaction in L-threitol. Finally, AIM theory was applied to the optimized structures of both polyols. The presence of an intramolecular hydrogen bond is

manifested by the existence of a bond critical point (BCP) with a (3, 1) topology between the hydrogen and the acceptor atom [21,22]. As can be seen in Table 2, no BCP was detected, meaning that these geometries do not have an intramolecular hydrogen bond as far as AIM theory is concerned. Since the various recognized methods for hydrogen bonding identification lead to doubtful conclusions, this means that we are in the borderline between this type of bonding and a van der Waals interaction involving atoms forced to be close together for structural reasons. In such cases, the specific characteristics of an H-bond play no role in the molecular conformations and, therefore, should not be taken into account. 3.2. Spectra interpretation The calculated spectra of erythritol and L-threitol obtained from their crystal molecular conformations are depicted in Figs. 2 and 3, respectively. These figures also include the experimental spectra of both compounds at 298.15 K, recorded from 4000 to 400 cm1. Tables 3 and 4 display the calculated vibrational frequencies and

(A)

(B) 4000

3500

3000

2500

1500

Wavenumber / cm

1000

500

-1

Fig. 2. Experimental infrared spectra of solid erythritol (A) at 298.15 K and calculated spectrum obtained at the B3LYP/6-311++G** level of theory (B). This spectrum was simulated using Lorentzian functions centered at the calculated (scaled) frequencies and with a bandwidth-at-half height equal to 2 cm1. Calculated frequencies were scaled by the following scale factors: 0.948 for the OH stretching region, 0.963 for the CH stretching region and 0.978 for all the other vibrations.

Table 2 Geometrical parameters, NBO stabilization energies and results of the topological analysis for the possible intramolecular H-bonds in the optimized molecular crystal conformations of erythritol and L-threitol.

a

Compound

Interactiona

O  H/Å

OAH  O/°

E(2)/kJ mol1

(3, 1) BCP

Erythritol L-threitol

O(1)AH  O(2)/O(4)AH  O(3) O(2)AH  O(3)

2.47 2.17

102.7 114.1

0.54 5.77

No No

The two possible intramolecular interactions in erythritol are symmetry-related.

159

A.J. Lopes Jesus, J.S. Redinha / Journal of Molecular Structure 938 (2009) 156–164

Table 3 Comparison of the experimental (T = 298.15 K) and calculated spectra of erythritol.

(A)

(B) 4000

3500

3000

2500

1500

Wavenumber / cm

1000

500

-1

Fig. 3. Experimental infrared spectra of solid L-threitol (A) at 298.15 K and calculated spectrum obtained at the B3LYP/6-311++G** level of theory (B). This spectrum was simulated using Lorentzian functions centered at the calculated (scaled) frequencies and with a bandwidth-at-half height equal to 2 cm1. Calculated frequencies were scaled by the following scale factors: 0.948 for the OH stretching region, 0.963 for the CH stretching region and 0.978 for all the other vibrations.

their approximate description obtained by animation of the vibrational modes using the GaussView program. From the theoretical calculated spectra and other arguments described along the text, the assignment of the experimental spectra is given in Tables 3 and 4 for erythritol and L-threitol, respectively. An important observation from the comparison of the spectra of the two compounds is the much simpler spectrum of erythritol. The existence of an inversion center in the crystal molecular conformation of erythritol causes some of its vibrational transitions to be infrared inactive and favors the coupling of the vibrational modes. This decreases the number of bands in erythritol. In the discussion presented below, two spectral regions were considered: 4000–2500 cm1 in which the stretching vibrations of OH and CH groups are located and <1500 cm1 where angular deformations of CH and COH, together with CO stretching vibrations take place. 3.2.1. Region 4000–2500 cm1 In this region, the experimental spectra of erythritol and L-threitol at 298.15 K show a strong overlap of a great number of bands (Figs. 2 and 3). In attempting to get a better resolution, spectra of both compounds were recorded from 298.15 K down to 15 K. Although a substantial improvement of the bands’ resolution is achieved by temperature decreasing (see Figs. 4 and 5), overlapping still remains at temperatures as low as 15 K. Thus, the careful interpretation of the spectra requires their decomposition into individual components. This was performed by curve-fitting analysis using Lorentzian or Gaussian band shape functions. As seen below, it is possible to identify in the region under consideration a frequency range corresponding to the OH stretching (4000– 3000 cm1) and to CH stretching (3000–2900). The absorptions between 2900 and 2600 cm1 result from non-fundamental vibration modes. Figs. 4 and 5 show the experimental spectra of the two compounds in the 3800–2500 cm1 spectral region at 298.15 K and 15 K. In these figures, the absorptions in the OH stretching region are resolved into the respective component bands. The values of their characteristic parameters are given in Tables 5 and 6. At 298.15 K, the erythritol spectrum exhibits three bands with a frequency of maximum absorption (mmax) at 3414, 3256 and 3154 cm1 and labeled as 1, 2 and 3, respectively (Fig. 4, Table 5). Band 2 is much stronger than the other two bands which, in turn, have a similar intensity. Pronounced modifications in the spectra are observed as the temperature decreases; the band

Experimentala (KBr pellet)

Calculated (conformation A) (B3LYP/6-311++G**)

m/cm1

m/cm1b

Icalc/km mol1

– – 3414 (sh,s) 3256 (vs) 3154 (sh,s) 2969 (s) 2954(s) 2925 (m) 2908 (s) 2895 (sh,w) 2817 (w) 2654 1458 (w) 1415 (s)

3652 3615 – – – 2981 – 2935 2906 – – – 1470 1382

95.8 85.4 – – – 48.9 – 58.8 78.1 – – – 11.9 66.8

1366 (w)

1355

12.2

–

1350

6.9

1306 (vw) 1274 (m) 1256 (s)

– 1248 1218

– 37.4 74.1

1218 (w)

1146

56.3

1081 (vs)

1058

171.6

1055 (vs)

1023

142.2

968 (s) 918 (vw) 884 (s)

951 – 859

48.7 – 42.1

864 (w) 700 (multiplet) 618 (s) – –

– – 596 445 400

– – 41.4 129.0 194.0

Approximate descriptionc

mO(2)H + mO(3)H mO(1)H + mO(4)H FR

mOHinter mOHinter masC(1)H2 + masC(4)H2 –

mC(2)H + mC(3)H msC(1)H2 + msC(4)H2    dC(1)H2 + dC(4)H2 xC(1)H2 + xC(4)H2 dCO1H + dCO4H cC(2)H + cC(3)H dCO(2)H + dCO(3)H dCO(1)H + dCO(4)H dC(1)H + dC(4)H – dC(2)H + dC(3)H twC(1)H2 + twC(4)H2 dC(2)H + dC(3)H dCO(2)H + dCO(3)H dCO(2)H + dCO(3)H dCO(1)H + dCO(4)H cC(2)H + cC(3)H mCO(2) + mCO(3) mCO(1) + mCO(4) mCO(2) + mCO(3) mCO(1) + mCO(4) dCO(1)H + dCO(4)H qC(1)H2 + qC(4)H2 – mCC qC(1)H2 + qC(4)H2 – sOHinter dCCO sO(1)H + sO(4)H sO(1)H + sO(4)H

a Intensities are given in a qualitative way: vs very strong; s, strong; m, medium, w, weak; vw, very weak; sh, shoulder. b Calculated frequencies are scaled by the following scaling factors: 0.948 for the OH stretching region, 0.963 for the CH stretching region and 0.978 for all the other vibrations. c Abbreviations: m, stretching; d, in-plane bending; c, out-of-plane bending; x, wagging; q, rocking; s, torsion; s, symmetric; as, asymmetric; op, out-of-phase vibration. By symmetry, all coupling modes are out-of-phase. FR = Band resulting from a Fermi resonance effect. OHinter refers to OH groups involved in intermolecular hydrogen bonds. * Overtones or combination bands (see text for details).

overlapping diminishes and the location of the peaks is better defined. Band 2 is split into two new bands with mmax = 3234 cm1 (2a) and mmax = 3190 cm1 (2b). Unlike the lower frequency bands, which become relatively narrow on cooling, band 1 remains broad and its relative intensity increases as temperature decreases. Apparently, this band does not correspond to a fundamental vibrational mode as will be confirmed by deuteration. Another effect of cooling is the displacement of the bands towards lower frequencies. As the temperature decreases from 298.15 to 15 K bands 1 and 3 are red-shifted by 41 and 30 cm1, respectively. Bands 2a and 2b are displaced by 22 and 66 cm1 relative to mmax of the original band 2. The theoretical spectrum of erythritol in this region exhibits two bands corresponding to the stretching vibration of the OH groups. That at higher frequency (3652 cm1) is assigned to the out-of-phase stretching vibration of the middle OH groups,

160

A.J. Lopes Jesus, J.S. Redinha / Journal of Molecular Structure 938 (2009) 156–164

Table 4 Comparison of the experimental (T = 298.15 K) and calculated spectra of L-threitol. Experimentala

Calculated (B3LYP/ 6-311++G**)

m/cm1

m/cm1b

Icalc/km mol1

– – – – 3372 3278 3215 3134 2973 2966 2947 2939 2927 2906 2881 2831 1458 – 1412 – – 1370 1357 1322 – 1298 1274 – 1218

(vw)

3660 3636 3634 3567 – – – – 2993 2965 – 2938 2923 2918 2917 – 1473 1472 1402 1392 1376 1362 1358 1331 1329 1312 1243 1223 1157

50.2 37.0 27.0 53.8 – – – – 16.3 41.4 – 12.1 15.6 34.0 51.3 – 1.8 5.2 19.3 20.6 2.1 22.2 28.2 5.7 5.5 1.7 50.5 14.1 17.6

1193 (sh,vw) 1178 (w) 1118 (s) – – 1056 (s) 1035 (vs) 1025 (s) 991 (m) 963 (s) 876 (vw) – 719 (multiplet) 660 (w) 560 (vw) 494 (vw) 472 (w)

– 1118 1085 1059 1043 1027 1006 997 968 939 – 750 – 628 536 – 482

– 34.4 68.4 2.7 24.1 74.1 111.0 90.0 4.4 46.2 – 5.2 – 14.7 3.1 – 167.3

(sh,vs) (vw) (m) (sh,m) (m) (m) (w) (w) (m) (m) (m) (sh,w) (broad) (broad)

(w) (sh) (w) (w) (vw)

Approximate descriptionc

298 K mO(3)H mO(1)H mO(4)H mO(2)H FR + water absorption mOHinter mOHinter mOHinter masC(4)H2 masC(1)H2 – mC(2)H mC(3)H msC(1)H2 msC(4)H2  dC(1)H2 dC(4)H2 cC(3)H cC(2)H + dCO(2)H xC(1)H2dC(2)H xC(4)H2 + dCO(4)H xC(1)H2 + dCO(1)H dC(3)H + dCO(1)H + dCO(4)H dCOH + xCH2 dC(2)H + dC(3)H dCO(3)H + dCO(2)H dCO(2)H + cC(2)H twC(1)H2 + dCO(1)H + dCO(3)H + dC(3)H – twC(4)H2 + dCO(4)H mC(2)C(3) mC(1)C(2) mC(4)O mCO mC(1)O mC(3)C(4) + dCO(3)H qC(4)H2 qC(1)H2 – mC(2)C(3) + qC(1)H2 + qC(4)H2 sOHinter dC(2)C(3)O(3) + dC(3)C(2)O(2) dCCO; dCCC – sO(2)H

a Intensities are given in a qualitative way: vs very strong; s, strong; m, medium, w, weak; vw, very weak; sh, shoulder. b Calculated frequencies are scaled by the following scaling factors: 0.948 for the OH stretching region, 0.963 for the CH stretching region and 0.978 for all the other vibrations. c Abbreviations: m, stretching; d, in-plane bending; c, out-of-plane bending; x, wagging; q, rocking; s, torsion; s, symmetric; as, asymmetric. FR = Band resulting from a Fermi resonance effect. OHinter refers to OH groups involved in intermolecular hydrogen bonds. * Overtones or combination bands (see text for details).

whereas the band at lower frequency (3615 cm1) corresponds to the out-of-phase stretching vibration of the terminal groups (see Table 3). The comparison of the theoretical and experimental spectra leads to the conclusion that the OH groups in the crystalline erythritol are involved in intermolecular hydrogen bonds. Indeed, the mmax of the OH stretching bands are shifted towards lower frequencies in the experimental spectrum relative to the theoretical one. Besides the fundamental OH stretching vibrations, other bands resulting from Fermi-resonance effects or vibrational coupling between neighboring OH groups can also be present, increasing the spectral complexity. To check for such effects, spectra of the

15 K 3800 3600 3400 3200 3000 2800 2600

Wavenumber / cm-1 Fig. 4. Experimental spectra (bold lines) and deconvoluted bands by curve-fitting (thin lines) of erythritol in the OH stretching region at 298.15 and 15 K. Goodness of fit: v2 = 1.5  104 and r = 0.999 (upper spectrum); v2 = 4.2  104 and r = 0.998 (bottom spectrum). All deconvoluted bands have a Lorentzian line-shape. Deconvoluted bands are labeled as 1, 2, 3 in the upper spectrum and as 1, 2a, 2b and 3 in the bottom spectrum, from the higher to lower frequencies, respectively.

298 K

15 K 3800 3600 3400 3200 3000 2800 2600 -1

Wavenumber / cm

Fig. 5. Experimental spectra (bold lines) and deconvoluted bands by curve-fitting (thin lines) of L-threitol in the OH stretching region at 298.15 and 15 K. Goodness of fit: v2 = 5.3  106 and r = 0.999 (upper spectrum); v2 = 1.7  105 and r = 0.998 (bottom spectrum). The deconvoluted band at higher frequency is Gaussian while all the others have a Lorentzian line-shape. Deconvoluted bands are labeled as 1, 2, 3 and 4 in the upper spectrum and as 1, 2, 3a, 3b and 4 in the bottom spectrum, from the higher to lower frequencies, respectively.

partially-deuterated compounds (percentage of deuteration is about 30%) were also traced at different temperatures. The OH and OD spectral regions at 15 K are displayed in Fig. 6 and the bands observed in the OD region (labeled as 2a0 , 2b0 and 30 ) are

161

A.J. Lopes Jesus, J.S. Redinha / Journal of Molecular Structure 938 (2009) 156–164 Table 5 Peak frequency (mmax) and relative area of the band components obtained by curve fitting of the OH and OD stretching regions at 298 and 15 K for erythritol. Band component

Temperature/K 298

a

15

mmax/cm1

Relative area (%)a

OH 1 2

3414 3256

– 84.3

3

3154

12.2

OD 10 20

– 2430

– 83.5

30

2378

16.5

m/cm1

Relative area (%)a

2a 2b

3373 3234 3190 3124

– 54.8 20.6 24.6

2a0 2b0

– 2412 2384 2343

– 50.5 27.7 21.8

(A)

(B)

The integrated area of band 1 was not considered.

Table 6 Peak frequency (mmax) and relative area of the band components obtained by curve fitting of the OH and OD stretching regions at 298 and 15 K for L-threitol. Band component

3600

Temperature/K 298

mmax/cm1

a

15 Relative area (%)

m/cm1

3364 3257 3203 3163 3070

– 18.5 17.2 60.3 4.0

2477 2431 2386 2363 2287

– 11.7 4.8 64.7 18.8

OH 1 2 3

3372 3278 3215

– 22.7 67.3

4

3134

10.1

OD 10 20 30

2520 2454 2398

– 25.2 59.1

40

2324

15.7

3a 3b

3a0 3b0

Relative area (%)a

The integrated area of bands 1 and 10 were not considered.

characterized in Table 5. As can be seen in Fig. 6, band 1 has no counterpart in the OD region, while the other three bands (2a, 2b and 3) have corresponding ones in the lower frequency region (2a0 , 2b0 and 30 ). In both regions, the relative intensities of the three bands are similar (Table 5). These observations confirm that band 1 does not correspond to a fundamental mode, bands 2a, 2b and 3 are assigned to three fundamental OH stretching modes, and no vibrational coupling between the OH groups exists. From the OH and OD band positions (see Table 5), the value found for the isotopic ratio is 1.34, a figure close to that found for other carbohydrates [23,24]. Band 1 is localized at a frequency where bound water also absorbs [25]. In spite of the care taken to keep and handle the samples in a water-free atmosphere, the following experiment was undertaken to investigate whether or not this band could correspond to a water vibration: a pellet of erythritol dispersed in KBr was heated inside the spectroscopic cell at a temperature 10 °C above the melting point (ca. 391 K) and the liquid was then crystallized by gradually cooling to 100 K and re-heated to 300 K. This procedure leads to the formation of the crystalline form of erythritol [26]. The spectrum of the solid thus obtained is identical to that of the original compound. Therefore, the presence of water should be ruled out. This broad band is actually a non-fundamental band. It may be a result from a Fermi resonance effect between a combination or overtone of the bending or stretching of the COH groups and a fundamental OH stretching band.

3400

3200

3000

2600

Wavenumber / cm

2400

2200

-1

Fig. 6. Experimental spectra (bold lines) and deconvoluted bands (thin lines) of erythritol (A) and L-threitol (B) at 15 K in the OH and OD stretching regions. In the OD region the deconvoluted bands are labeled as 2a0 , 2b0 and 30 in the upper spectrum and as 10 , 20 , 3a0 , 3b0 and 40 in the bottom spectrum, from the higher to lower frequencies, respectively.

Concerning L-threitol, four bands are present in the theoretical spectrum, corresponding to the stretching vibration modes of the four OH groups. Since mO(1)H and mO(4)H are only 2 cm1 apart they appear in the theoretical spectrum as a single band, as can be seen in Fig. 3. The higher frequency band (3660 cm1) corresponds to mO(3)H. The next two bands, 3636 and 3634 cm1, are assigned to the mO(1)H and mO(4)H, respectively, and that at lower frequency (3567 cm1) is due to mO(2)H. The experimental spectrum of L-threitol at 298.15 K (Fig. 5) shows four overlapped bands. Since band 3 is split into two (3a and 3b) at low temperature, five bands are observed at 15 K. Band 1 (mmax = 3364 cm1 at 15 K) is very broad and intense. Although the intensity of the corresponding band in the OD region (band 10 ) is greatly reduced, it does not completely disappear (see Fig. 6). Apparently, band 1 is partially due to a non-fundamental vibrational mode as in erythritol and partially to a fundamental vibration of any foreign deuterable compound, e.g., water. The weak absorption observed at 1630 cm1 and assigned to the bending vibration of water is an argument in favor of the presence of this substance. The strong hygroscopicity of this compound [27] explains the difficulty in getting a sample free of water to the spectroscopic experiments. Due to the high glass forming tendency of L-threitol [28], we were not able to compare the spectra of the original solid with that of a product prepared from melt, as done for erythritol. As conclusion, four bands assigned to the stretching vibration of OH groups (2, 3a, 3b and 4) involved in intermolecular hydrogen bonds are evidenced by the spectrum of the solid L-threitol at 15 K. The strength of an H-bond can be estimated from the frequency shift (Dm) of the stretching vibration of the OH group involved in an H-bond (mOHinter) relatively to that of the group free from any interaction of this type (mOHfree), Dm = mOHfree  mOHinter. These shifts were calculated relatively to 3652 cm1 in erythritol, and 3660 cm1 in L-threitol. Empirical correlations between Dm and

162

A.J. Lopes Jesus, J.S. Redinha / Journal of Molecular Structure 938 (2009) 156–164

the enthalpy of the respective H-bond have been worked out by several authors [29–31]. Using the one proposed by Iogansen [31] to the experimental OH stretching frequencies at 15 K, the values of this thermodynamic property for the different H-bond in the systems under study range from 27–31 kJ mol1 in erythritol and 26–32 kJ mol1 in L-threitol. These values show that there are no significant differences between the strengths of the hydrogen bonds of the two compounds. This agrees with the values estimated for the enthalpy of interaction in the solids on the basis of calorimetric measurements and theoretical calculations [11]. Concerning the CH stretching region (3000–2900 cm1), the calculated spectrum of erythritol exhibits three bands localized within a narrow interval of 75 cm1. The bands at higher and lower frequencies (2981 and 2906 cm1) are assigned to the asymmetric and symmetric CH2 stretching modes, respectively, which are combined as described in Table 3. The band predicted at 2935 cm1 is assigned to stretching vibration of the two CH groups. In this spectral region, six vibrational modes are predicted for L-threitol. However, only five are well discriminated in the theoretical spectrum because msC(1)H2 and msC(4)H2 appear at almost the same frequency. From a structural point of view, the difference between the calculated spectra of the two isomers in this spectral region arises from the aforementioned symmetry difference. No significant differences are found between the theoretical and experimental spectra (see Figs. 2 and 3). Thus, little information on the structure can be taken from this region. The experimental spectra of both compounds show some relatively weak absorption bands between 2900 and 2600 cm1. These bands are not predicted in the calculated spectrum and consequently they cannot be assigned to fundamental CH stretching vibrations. At 15 K, the spectra of erythritol present three broad bands with mmax at 2890, 2826 and 2663 cm1. The corresponding absorptions of L-threitol are not so well discriminated as they are overlapped with those of the CH groups (Fig. 5). In this spectral region, the lowest frequency band is located at mmax = 2890 cm1, which lies outside the CH stretching region for this molecule. Since all these bands disappear upon deuteration, they might be due to overtones or combination bands involving COH deformation modes which are found in the spectral region between 1400 and 1300 cm1. As the maxima of these weak bands are too far from those corresponding to the fundamental OH stretching bands (Dm = 235–530 cm1), no significant Fermi-resonance interaction is expected to occur between these bands. 3.2.2. Region below 1500 cm1 The 1500–1000 cm1 spectral region is characterized by inplane and out-of-plane bending vibrations of the CH groups, COH bendings, as well as CO stretching modes. Thus, the spectra of both compounds are complex due either to the existence of a large number of bands or to the strong coupling between the COH bendings and some other vibration modes (see Tables 3 and 4). For this reason, it is difficult to assign a band to a specific group and, therefore, the structural information taken from this spectral region is somewhat limited. As can be seen in Figs. 2 and 3, despite the frequency displacement between the theoretical and experimental spectra, there is a good match between them, particularly in erythritol. The frequency shift of the experimental bands relative to the theoretical ones is, in general, towards the higher frequencies, both for stretching and bending modes. Fig. 7 depicts the fingerprint region of erythritol and L-threitol before (bold spectra) and after partial deuteration (thin spectra). Comparison of these spectra yields more information on the composition of the bands. In particular, when the vibration of a deuterable group is coupled with that of a non-deuterable one, the variation of the band profile upon deuteration gives an indication

(A)

(B) 1600 1400 1200 1000

800

600

400

-1

Wavenumber / cm

Fig. 7. Spectra of non-deuterated (bold lines) and partially-deuterated (thin lines) erythritol (A) and L-threitol (B) in the region below 1500 cm1 at 298.15 K.

of the contribution of each vibration mode. This effect can be observed in erythritol for the bands located at 1415, 1218 and 1055 cm1 and in L-threitol for the bands at 1370, 1218 and 1025 cm1. In all these bands, CH bendings or CO stretching modes are coupled with COH bendings. The deuteration of the COH group decreases the band intensity and a new one appears at lower frequency. For example, the comparison of the experimental spectra of erythritol before and after deuteration shows that the intensity of the band located at 1055 cm1 decreases considerably, while a band at 1009 cm1 appears in the spectrum of the deuterated solid. The red-shift of the above-mentioned band is related to the weight of dCOH in its vibrational composition. Below 1000 cm1 the most important absorptions appear at ca. 700 cm1 for erythritol and ca. 720 cm1 for L-threitol. These two broad bands have no equivalents in the theoretical spectra and are red-shifted by deuteration to ca. 520 and ca. 514 cm1, respectively. These absorptions correspond to the torsional vibration of the OH groups involved in intermolecular H-bonds. This spectral region has been the object of attention by Rozenberg et al. [30,32]. Their results show the existence of at least two bands in the erythritol spectrum assigned to the out-of-plane OH vibrations, whereas the L-threitol spectrum contains additional H-bonded systems. These results are consistent with those provided in the present work concerning the analysis of the OH stretching region. 3.3. Correlation between the spectral and structural data As stated above, information on the crystal structure of both compounds from diffraction methods is available in literature [12,13]. A further stage in the structural characterization of these isomers can be achieved by complementing the diffraction data with the information taken from vibrational spectroscopy. To achieve this target we need to correlate the data obtained from the two sources. Three different H-bonds are found in the neutron diffraction crystal structure of erythritol. These are characterized on geomet-

163

A.J. Lopes Jesus, J.S. Redinha / Journal of Molecular Structure 938 (2009) 156–164 Table 7 Correlation between the spectroscopic and structural data.a OH stretching band

Intermolecular H-bond

Label

O  H/Å

OAH  O/°

Type

a

Erythritol 2a 2b 3

O(3)AH  O(2) or O(2)AH  O(3) (conformation B) O(3)AH  O(2) or O(2)AH  O(3) (conformation A) O(4)AH  O(1) or O(1)AH  O(4)

a a0 b

1.85 1.79 1.70

163.9 164.5 173.2

L-Threitol 2 3a 3b 4

O(3)IIAH  O(2)II O(2)IAH  O(3)I; O(2)IIAH  O(3)II; O(2)IIIAH  O(3)III O(1)IAH  O(4)II; O(3)IAH  O(2)I; O(4)IIAH  O(1)III ; O(1)IIIAH  O(4)I; O(4)IIIAH  O(1)III O(4)IAH  O(1)II; O(1)IIAH  O(4)III; O(3)IIIAH  O(2)III

c d e f

O  O/Å 2.68 2.72 2.71 2.69

144.8 155.1 163.1 176.2

Structural data were taken from references [12,13].

rical grounds by the O  H distances and OAH  O angles given in Table 7. These bonds are designated as a, a0 and b. The first two involve the middle OH groups of conformations B and A, respectively, and the later the terminal OH groups. To provide the correspondence between geometrical and spectral data we assume that smaller O  H distances and higher OAH  O angles correspond to a greater red-shift. Doing so, we can establish the correlation given in Table 7. Hence, component band 3 is assigned to the stretching vibration of the terminal OH groups, while bands 2a and 2b bands correspond to the stretching vibration of the middle OH groups of conformations B and A, respectively. A more complex structure is exhibited by L-threitol [12]. The three conformations existing in the crystal structure give rise to twelve different intermolecular H-bonds. To identify and characterize representative groups of H-bonds, a k-means cluster analysis of the O  O distances and OAH  O angle values was carried out (O  H distances determined by X-ray are not as reliable as the O  O distances because the position of the hydrogen atoms are not as well defined by this technique). Four clusters of intermolecular H-bonds were considered, as no significant decrease in the variance within each cluster was observed by increasing the number of clusters. The H-bond clusters were labeled as c, d, e and f, as defined in Table 7. The first two connect the middle OH groups, while the latter preferentially involve the terminal groups. Using the same arguments as those used above for erythritol, it is possible to establish the correlation given in Table 7. The results of this correlation show that the two lower frequency bands (3b and 4) are assigned to the stretching vibration of the terminal OH groups while those at higher frequencies (2 and 3a) correspond mainly to the stretching vibration of the middle OH groups.

4. Conclusions Infrared spectra of erythritol and L-threitol, as well as of their deuterated forms, were obtained at temperatures from 298.15 to 15 K. Three intermolecular hydrogen bonds between the OH groups were identified in erythritol and four in L-threitol. The correlation between the red-shift of the OH stretching bands with the geometrical parameters taken from the crystallographic data allowed assigning these bands to specific OH groups. This achievement is important as far as these interactions are now characterized on both spectroscopic and geometric grounds. Besides the fundamental vibration modes, some other bands resulting from Fermi-resonance effects were also identified. Deuteration and temperature decrease were found to be determinant in the spectra interpretation. The optimized molecular crystal conformations were used to obtain the reference spectra. These structures were studied in detail, giving particular attention to the possibility of establish-

ment of intramolecular hydrogen bonds. The conclusion drawn from the methods used to clarify this point is that no significant H-bonding takes place in these conformations. The present research is a valuable contribution to the spectroscopic characterization of erythritol and L-threitol. Besides their structural relevance, we hope that the data now available will be useful in many other studies involving these and related compounds. Acknowledgments The authors thank the research group of Prof. Rui Fausto (Laboratory of Molecular Cryospectroscopy and Biospectroscopy, Department of Chemistry, University of Coimbra), and in particular to Susana Jarmelo and Igor Reva, for their help in the low temperature infrared spectroscopy experiments. References [1] A. Zumbe, A. Lee, D. Storey, Br. J. Nutr. 85 (2001) S31. [2] T.M.S. Wolever, A. Piekarz, M. Hollands, K. Younker, Can. J. Diabetes 26 (2002) 356. [3] American Dietetic Association, J. Am. Diet. Assoc. 104 (2004) 255. [4] D. Traini, P.M. Young, M. Jones, S. Edge, R. Price, Eur. J. Pharm. Sci. 27 (2006) 243. [5] S. Ohmori, Y. Ohno, T. Makino, T. Kashihara, Int. J. Pharm. 278 (2004) 447. [6] R. Usha, T. Ramasami, Colloids Surf. B 61 (2008) 39. [7] P. Del Vecchio, D. Esposito, L. Ricchi, G. Barone, Int. J. Biol. Macromol. 24 (1999) 361. [8] K.B. Storey, Comp. Biochem. Physiol. A 117 (1997) 319. [9] M.T.C. Martins Costa, J. Mol. Struct. (THEOCHEM) 729 (2005) 47. [10] S.C. Eggers, T.E. Acree, R.S. Shallenberger, Food Chem 68 (2000) 45. [11] A.J.L. Jesus, L.I.N. Tomé, J.S. Redinha, M.E. Eusébio, J. Phys. Chem. B 109 (2005) 18055. [12] J. Kopf, M. Morf, B. Zimmer, E.T.K. Haupt, O. Jarchow, P. Koll, Carbohydr. Res. 247 (1993) 119. [13] C. Ceccarelli, G.A. Jeffrey, R.K. McMullan, Acta Crystallogr. B 36 (1980) 3079. [14] M.J. Frisch, G.W. Trucks, H.B. Schlegel, G.E. Scuseria, M.A. Robb, J.R. Cheeseman, J.A. Montgomery Jr., T. Vreven, K.N. Kudin, J.C. Burant, J.M. Millam, S.S. Iyengar, J. Tomasi, V. Barone, B. Mennucci, M. Cossi, G. Scalmani, N. Rega, G.A. Petersson, H. Nakatsuji, M. Hada, M. Ehara, K. Toyota, R. Fukuda, J. Hasegawa, M. Ishida, T. Nakajima, Y. Honda, O. Kitao, H. Nakai, M. Klene, X. Li, J.E. Knox, H.P. Hratchian, J.B. Cross, V. Bakken, C. Adamo, J. Jaramillo, R. Gomperts, R.E. Stratmann, O. Yazyev, A.J. Austin, R. Cammi, C. Pomelli, J.W. Ochterski, P.Y. Ayala, K. Morokuma, G.A. Voth, P. Salvador, J.J. Dannenberg, V.G. Zakrzewski, S. Dapprich, A.D. Daniels, M.C. Strain, O. Farkas, D.K. Malick, A.D. Rabuck, K. Raghavachari, J.B. Foresman, J.V. Ortiz, Q. Cui, A.G. Baboul, S. Clifford, J. Cioslowski, B.B. Stefanov, G. Liu, A. Liashenko, P. Piskorz, I. Komaromi, R.L. Martin, D.J. Fox, T. Keith, M.A. Al-Laham, C.Y. Peng, A. Nanayakkara, M. Challacombe, P.M.W. Gill, B. Johnson, W. Chen, M.W. Wong, C. Gonzalez, J.A. Pople, Gaussian, Inc., Wallingford, CT, 2004. [15] F. Weinhold, NBO 5.0 Program Manual Theoretical Chemistry Institute, Univ., Wisconsin, Madison, 2001. [16] F.W. Biegler-König, R.F.W. Bader, W.-H. Tang, J. Comput. Chem. 3 (1982) 317. [17] R.F.W. Bader, in: McMaster University, Hamilton, Ontario, Canada, 1991. [18] A.J.L. Jesus, L.I.N. Tomé, M.T.S. Rosado, M.L.P. Leitão, J.S. Redinha, Carbohydr. Res. 340 (2005) 283. [19] T. Steiner, Angew. Chem. Int. Ed. 41 (2002) 48.

164

A.J. Lopes Jesus, J.S. Redinha / Journal of Molecular Structure 938 (2009) 156–164

[20] F. Weinhold, C.R. Landis, Valency and Bonding: A Natural Bond Orbital Donor– Acceptor Perspective, Cambridge University Press, New York, 2005. [21] R.F.W. Bader, Atoms in Molecules – A Quantum Theory, University Press, Oxford, 1990. [22] L.F. Pacios, P.C. Gómez, J. Comput. Chem. 22 (2001) 702. [23] E.T.G. Lutz, J.H. van der Maas, J. Mol. Struct. 324 (1994) 123. [24] M. Rozenberg, A. Loewenschuss, Y. Marcus, Carbohydr. Res. 328 (2000) 307. [25] L. Schriver-Mazzuoli, A. Schriver, A. Hallou, J. Mol. Struct. 554 (2000) 289. [26] A.J.L. Jesus, C.C.S. Nunes, J.S. Redinha, 2008, Unpublished results.

[27] S. Cohen, Y. Marcus, Y. Migron, S. Dikstein, A. Shafran, J. Chem. Soc. Faraday Trans. 89 (1993) 3271. [28] B. Wowk, M. Darwin, S.B. Harris, S.R. Russell, C.M. Rasch, Cryobiology 39 (1999) 215. [29] M.S. Rozenberg, Spectrochim. Acta A 52 (1996) 1559. [30] M. Rozenberg, A. Loewenschuss, Y. Marcus, Carbohydr. Res. 304 (1997) 183. [31] A.V. Iogansen, Spectroc. Acta A 55 (1999) 1585. [32] M. Rozenberg, A. Loewenschuss, H.-D. Lutz, Y. Marcus, Carbohydr. Res. 315 (1999) 89.