Delicate Balance of Hydrogen Bonding Forces in d-Threoninol

Article pubs.acs.org/JPCA

Delicate Balance of Hydrogen Bonding Forces in D‑Threoninol Vanesa Vaquero-Vara,†,‡,§ Di Zhang,‡ Brian C. Dian,‡ David W. Pratt,*,†,§ and Timothy S. Zwier*,‡ †

Department of Chemistry, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, United States Department of Chemistry, Purdue University, West Lafayette, Indiana 47907, United States § Department of Chemistry, University of Vermont, Burlington, Vermont 05405, United States ‡

S Supporting Information *

ABSTRACT: The seven most stable conformers of D-threoninol (2(S)-amino-1,3(S)butanediol), a template used for the synthesis of artificial nucleic acids, have been identified and characterized from their pure rotational transitions in the gas phase using chirped-pulse Fourier transform microwave spectroscopy. D-Threoninol is a close analogue of glycerol, differing by substitution of an NH2 group for OH on the C(β) carbon and by the presence of a terminal CH3 group that breaks the symmetry of the carbon framework. Of the seven observed structures, two are H-bonded cycles containing three H-bonds that differ in the direction of the H-bonds in the cycle. The other five are H-bonded chains containing OH···NH···OH H-bonds with different directions along the carbon framework and different dihedral angles along the chain. The two structural types (cycles and chains of H-bonds) are in surprisingly close energetic proximity. Comparison of the rotational constants with the calculated structures at the MP2/6-311++G(d,p) level of theory reveals systematic changes in the H-bond distances that reflect NH2 as a better H-bond acceptor and poorer donor, shrinking the H-bond distances by ∼0.2 Å in the former case and lengthening them by a corresponding amount in the latter. Thus revealed is the subtle effect of asymmetric substitution on the energy landscape of a simple molecule, likely to be important in living systems.

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INTRODUCTION

play a key role in catalyzing the formation of intermolecular assemblies. In what follows, we use the technique of chirped-pulse Fourier transform microwave (CP-FTMW) spectroscopy to examine the conformational properties of D-threoninol (DTN) in the gas phase. Like glycerol (see below), DTN has three adjacent functional groups, but an amino (−NH2) group replaces the central −OH group in glycerol.

Nature uses ribose and deoxyribose as scaffolds for building nucleic acids to carry genetic codes.1 However, recently, it has been discovered that simple acyclic diols like propylene glycol2 and 2(S)-amino-1,3(S)-butanediol (D-threoninol)3 may be used to synthesize artificial oligonucleotides that spontaneously fold with complementary strands into double-helical structures, some more stable than natural DNA. This is an exciting result because such findings raise the prospect of designing new artificial duplexes (synthetic “foldamers”) that do not rely on rigid preorganization of the single strand backbone, thereby creating a range of artificial duplexes with binding properties that can be fine-tuned. Intrigued by these results, we were curious to learn more about the common structural feature(s) exhibited by these apparently dissimilar systems. Several important chemical and biochemical scaffolds have hydrogen bonding groups spread across adjacent carbons in an alkyl chain. Many of these incorporate hydroxyl (−OH) groups that can form networks of intramolecular OH···OH···OH hydrogen bonds (HBs). Indeed, earlier spectroscopic studies of gas-phase molecules have shown that glycerol, a prototypical molecule with −OH groups attached to the three adjacent carbons, and ribose, with three vicinal −OH groups and an additional “across-the-ring” −OH group, each exhibit cooperative HB networks, resulting in either closed- or open-chain structures.4−6 These structures, with exposed lone pairs of electrons on one or more faces, could © 2014 American Chemical Society

Applications of the OH/NH2/OH scaffold in living systems include the molecules serinol, a precursor in the synthesis of antibiotics,7 and sphingosine, which serves as an anchor in the phospholipid bilayer.8 The −NH2 group is known principally as a HB acceptor to its nitrogen lone pair, but −NH2 groups also can engage in HB donation. Indeed, our results show that the stable DTN conformers also exhibit cooperative HB networks, as in glycerol, though substitution of −OH by −NH2 reveals a Special Issue: Kenneth D. Jordan Festschrift Received: November 4, 2013 Revised: January 4, 2014 Published: January 6, 2014 7267

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different conformational landscape arising from the stronger HB accepting character of the amino group.

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EXPERIMENTAL AND THEORETICAL METHODS Force field calculations using Amber were first performed with the MacroModel9 commercial program suite (10 000 iterations, 0.0001 convergence threshold), yielding 85 stable conformations of DTN with energies less than 50 kJ mol−1. These were then subjected to energy minimization using ab initio calculations at the MP2/6-311++G(d,p)10 level, with vibrational zero-point correction. In the CP-FTMW11 experiments, DTN, a white solid (mp 57−61°), was acquired from Sigma-Aldrich (97% purity) and used without further purification. Preliminary studies were performed using the mirror-horn instrument at the University of Pittsburgh;12 the majority of the experimental work was performed on the two-horn spectrometer at Purdue University.13 In the latter spectrometer, DTN was vaporized at 120° in a heating reservoir placed in front of a 1.8 mm General Valve nozzle and seeded in Ne (99% purity) at a backing pressure of 0.7 bar. Pulsed at a rate of 10 Hz, the gas mixture was expanded into a vacuum chamber (10−5 Torr) and exposed to a perpendicularly propagating microwave pulse that was chirped in 1 μs over the frequency range of 7.5−18.5 GHz. This 11 GHz bandwidth pulse was amplified by a 200 W traveling wave tube amplifier and broadcast into the chamber through a microwave horn antenna. A 20 μs free induction decay (FID) was collected with a second horn antenna, amplified with a 45 dB low-noise amplifier, and down converted for display and processing on a 12 GHz digital oscilloscope working at a sampling rate of 40 GS/s. The averaged signal from 10 000 gas pulses was background-subtracted to remove electrical noise and any residual harmonic frequencies.

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Figure 1. The seven most stable conformers of DTN calculated at the MP2/6-311++(g,p) level of theory and paired according to the dihedral angles of their functional groups. The direction α → β → γ (I) or γ → β → α (II) and the number of the HBs are given in parentheses. Their zero-point-corrected relative energies are also given in cm−1.

RESULTS Theoretical Predictions and Nomenclature. Fifteen conformations of DTN with energies within 500 cm−1 of the global minimum were predicted by the calculations, the seven lowest in energy of which are shown in Figure 1. The next seven are described in the Supporting Information (SI). Addition of a CH3 group to the backbone of glycerol breaks the molecular symmetry, generating two different conformations for each original structure in glycerol. This new methyl group also creates two chiral centers; thus, DTN (2S, 3S) is one of a family of four diastereomers with chemical formula C4H11NO2. Its mirror-image form, L-threoninol (2R, 3R), would share the same number of conformations with the same relative stability, while the other two allo forms, (2S, 3R) and (2R, 3S), would exhibit different conformational landscapes. In the present work, we focus attention on the conformers of DTN. These conformers fall into two classes, cyclic and chain structures, and are labeled according to the orientation of the functional groups, the number of intramolecular HBs, and the relative position of the heteroatoms. Two examples are shown to the right, I3(g+g−) and II3(g+g−). Here, the Roman numerals I and II denote the direction of the H-bonds along the carbon framework, α(OH) → β(NH) → γ(OH) (I) and γ(OH) → β(NH) → α(OH) (II), while the subscripts 2 and 3 give the number of hydrogen bonding interactions within the molecule, producing either H-bonded chains (2) or cycles (3). The low-energy structures all place the heavy atom substituents on the same side of the carbon framework in gauche

configurations. Dihedral angles between adjacent heavy-atom substituents along the carbon framework are given in parentheses, with angles within ±10° of +60° as g+ and those near −60° as g−. The first label gives the dihedral angle of N with respect to Oα and the second the dihedral angle of Oγ with respect to N.

Microwave Spectra. Figure 2 shows the experimental microwave spectrum of DTN over the range of 7.5−18.5 GHz. The spectrum contains hundreds of lines with widely varying intensities and likely includes separate contributions from several different conformers. Each conformer is expected to exhibit a unique pattern of lines, but the different conformers 7268

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conformation. Therefore, other methods must be used to assign the different sets of transitions to specific conformers. One parameter that proved useful in this regard is Ray’s asymmetry parameter, κ = (2B − A − C)/(A − C).17 This constant gives information about the shape of the molecule, with the limiting values of κ, −1 and +1, corresponding to prolate and oblate tops, respectively. As can be seen from Table 1, the seven lowest-energy conformers of DTN fall closer to the prolate limit but can still be divided into four different structural classes, based on the dihedral angles of the functional groups, κ = −0.45 for g+g+, κ = −0.70 for g−g+, κ = −0.80 for g+g−, and κ = −0.93 for g−g−. Clearly, the two sets of rotational constants A and B, associated with the most intense lines of the spectrum, belong to the same g+g− class because their experimental asymmetry parameters (−0.79 and −0.78) have values near −0.80. However, the remaining sets of constants, C through G, must belong to one of the other classes because their κ values are very different. We then proceeded to identify the other observed conformers of DTN. This was done by removing the more intense assigned rotational transitions of the more stable conformers from the experimental spectrum and then comparing the remaining, less intense lines with the predictions of theory. After many iterations, this process ultimately led to the identification of five new structures with different sets of rotational constants, all of which are summarized in Table 2. Altogether, we found two g+g+ forms, two g+g− forms, one g− g+ form, and two g−g− forms. Of these, the g−g+ structure is unique because it is the only one with a κ value near −0.70. Tentative assignments of the remaining spectra to specific conformers within each class follow from comparing the observed rotational constants and the relative intensities of a-, b-, and c-type lines in the spectra, with the predictions of theory. The projections of the dipole moment along the a-, b-, and c-axes is particularly important here because reorientations of the −OH or −NH2 groups can substantially change the orientation of the dipole. Ultimately, it was discovered that conformers with similar κ values could be distinguished by differences in their observed nuclear quadrupole splittings.18 These splittings arise from a coupling between the nuclear spin angular momentum I of a quadrupolar nucleus (I = 1 for 14N) and the angular

Figure 2. Pure rotational spectrum of DTN from 7.5 to 18.5 GHz.

have different moments of inertia and rotational constants; therefore, the overall spectrum is extremely complex. To deconvolute the experimental spectrum into the separate contributions of the different conformers, we first used ab initio theory to predict the rotational parameters of the predicted structures of DTN. Results for the seven lowest-energy conformers are listed in Table 1. Then, a semirigid-rotor model Hamiltonian14 was employed to predict the rotational transitions of the two most stable conformers, and JB9515 was used as a visualization tool to compare the predicted spectrum with the observed one. This led to the identification of several strong lines in the spectrum. The experimental frequencies of these lines were then input into Pickett’s SPFIT/SPCAT program,16 and refined values of the rotational constants were obtained. These are listed in Table 2. The rotational constants of some of the conformers are nearly the same, especially when they share a similar heavy atom configuration and differ primarily in the orientation of their −OH and −NH2 groups. For example, the experimental values of A, B, and C for the two more stable conformers are 3904, 1932, and 1701 and 3903, 1938, and 1693 MHz, respectively, making it difficult to assign them to a particular

Table 1. Calculated Rotational Parameters of the Seven Most Stable Conformations of DTN at the MP2/6-311+G(d,p) Level of Theory MP2/6- 311+G(d,p)

II3(g+g−)

I3(g+g−)

I2(g+g+)

II2(g−g−)

II2(g+g+)

II2(g−g+)

I2(g−g−)

Aa (MHz) B (MHz) C (MHz) κb μac (D) μb (D) μc (D) μT (D) χaad (MHz) χbb (MHz) χcc (MHz) ΔEMP2+ZPC (cm−1)e

3941 1936 1709 −0.80 1.3 2.7 1.3 3.3 −1.32 0.68 0.64 0

3924 1945 1704 −0.78 0.7 2.6 1.3 2.9 −4.91 2.36 2.55 45

3512 2064 1528 −0.46 1.6 0.4 0.9 1.9 −0.06 2.64 −2.59 61

4618 1579 1480 −0.94 1.4 0.8 1.0 1.9 0.74 0.44 −1.19 70

3461 2070 1523 −0.44 4.3 0.5 1.6 4.6 −3.60 1.68 1.92 134

4194 1732 1308 −0.71 3.0 2.0 1.7 4.0 −2.54 0.46 2.08 215

4550 1583 1463 −0.92 4.7 0.7 0.5 4.8 −4.85 2.38 2.46 216

a A, B, and C are the rotational constants. bκ is Ray’s asymmetry parameter, κ = (2B − A − C)/(A − C). cμa, μb, μc, and μT are the absolute values of the electric dipole moment components and the total dipole moment. dχaa, χbb, and χcc are the diagonal elements of the 14N nuclear quadrupole coupling tensor. eRelative energies including zero-point correction vibrational energies.

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Table 2. Experimental Rotational Parameters of the Seven Conformers Identified in the Spectrum A (Mhz) B (Mhz) C (Mhz) ΔJ (KHz) κ χAa (MHz) χBb (MHz) χCc (MHz) Nb σc/KHz a

A

B

C

D

E

F

G

3904.077(1)a 1931.925(1) 1701.108(1) 0.16(3) −0.79 −1.19(2) 0.49(3) 0.70(3) 31 10.8

3902.915(1) 1938.430(1) 1693.264(1) 0.17(3) −0.78 −3.88(1) 1.65(1) 2.23(1) 33 8.3

3513.696(2) 2037.084(1) 1515.886(1) 0.22(2) −0.48 0.08(2) 2.22(2) −2.30(2) 14 6.5

4584.786 (2) 1568.397(1) 1472.179(1)

3482.376(5) 2026.931(2) 1507.379(2) 0.31(5) −0.47 −3.1(1) 1.7(2) 1.4(2) 20 18.4

4171.110(2) 1722.480(1) 1301.685(1)

4525.5(4) 1570.279(2) 1460.121(2) 0.18(3) −0.93 −4.0(1) 3.0(7) 1.0(7) 15 15.6

−0.94 0.61(7) 0.33(5) −0.94(5) 22 13.8

−0.71 −2.04(7) 0.59(7) 1.45(7) 23 18.6

Errors in parentheses are expressed in units of the last digit. bNumber of fitted lines. cStandard deviation of the fit.

momentum of overall rotation, J, to give the resultant vector F = I + J; different orientations of I in the molecular frame have different energies owing to the interaction with a nonspherically symmetric electron distribution in the vicinity of the nucleus. The elements of the resulting tensor are obtained using the formula χgg = eQqgg, where χgg are the nuclear quadrupole coupling constant, eQ is the nuclear quadrupole moment (constant for every quadrupolar nucleus), and qgg is the electric field gradient, with reference to the principal inertial axes (g = a, b, and c). The different components in a quadrupole-split rotational transition are designated by F, which can take on specific values from (J − I) to (J + I), and obey the selection rule ΔF = 0, ±1. Ultimately, all transitions were fit to a Watson asymmetric rotor Hamiltonian corrected by the addition of quadrupole coupling terms.19 Figure 3 shows the quadrupole hyperfine patterns observed for the 22,0 ← 11,1 rotational transitions of the two g+g−

conformers also make possible an unambiguous assignation of the conformers C, D, E, F, and G to the I2(g+g+), II2(g−g−), II2(g+g+), II2(g−g+), and I2(g−g−) structures, respectively. Examination of the data in Tables 1 and 2 reveals that the theoretical and experimental rotational constants of a particular conformer are not identical; in most cases, differences of more than 10 MHz were found between the calculated and observed values. (Typically, the calculated constants are larger than the observed ones.) A small number of very weak signals remain unassigned and likely arise from conformers predicted to have higher energies and/or isotopomers of more stable structures.

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DISCUSSION A total of 172 lines have been observed and fit in the 7.5−18.5 GHz region of the pure rotational spectrum of DTN. These have been assigned to seven different conformers of the isolated molecule, whose relative energies (according to MP2) span a range of only 216 cm−1, as shown in Table 3. Also included in Table 3. Comparison of Relative Energies of the Seven Most Stable Conformations of DTN at the Indicated Levels of Theory (Including Zero-Point-Corrected Vibrational Energies)

ΔEMP2+ZPC (cm−1)a ΔEM052X+ZPC (cm−1)a ΔEB3LYP+ZPC (cm−1)a a

II3(g +g−)

I3(g +g−)

I2(g +g+)

II2(g− g−)

II2(g +g+)

II2(g− g+)

I2(g− g−)

0

45

61

70

134

215

216

0

72

345

273

477

499

336

0

68

177

87

179

144

132

All calculations utilized the 6-311++g(d,p) basis set.

this table are the results from two DFT methods, using M05-2X and B3LYP functionals. The three levels of theory all predict the two most stable conformers to be cyclic HB networks, in which the direction of the cycle is reversed [(αβγ) and (γβα)], whereas the remaining five structures are HB chains. The predicted relative energies of the seven observed conformers differ among the different levels of theory. This is similar to the results obtained for glycerol.5a In the case of glycerol, five conformers were assigned and identified with the aid of theory; one of these is cyclic, whereas the remaining four are chains. The existence of two low-energy cyclic structures in DTN may be traced to its lower symmetry. We also estimated the relative populations of the different DTN conformers using the relative transition intensities in the

Figure 3. Quadrupole hyperfine structure in the 220−111 rotational transitions of the two conformers exhibiting cyclic HB networks.

conformers. Clearly evident is the fact that the two patterns are different, arising from differences in the nuclear quadrupole coupling constants. Comparisons with theory clearly show that the conformer with the smaller coupling is the II3(g+g−) isomer that is predicted to be more stable and that the conformer with the larger coupling is the less stable I3(g+g−) isomer. The observed quadrupole patterns of the remaining 7270

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Figure 4. Calculated (MP2/6-31++G(d,p)) interconversion barriers involving pairs of conformers in DTN linked by internal rotation of the terminal acceptor −OH groups.

spectrum. Employing a method that is described elsewhere,20 the intensities of each of the lines assigned to each specific conformer were divided by the squares of the respective dipole moment components predicted by theory and then summed to obtain an estimate of the total number of each conformer present in the expansion. After normalizing the results for all seven structures, the different intensities were taken to be proportional to the relative populations of the different conformers, yielding the results A > D > B > E > C > F > G. This “landscape” is somewhat different from the predicted one, A > B > C, and so forth. Conformers A and B are the two H-bonded cycles with different directions of the H-bonds in the cycle, while D is the second most stable of the chain forms, lying only 25 and 9 cm−1 higher in energy (according to MP2) above conformers B and C, respectively. The different relative abundances obtained from experiment may be influenced by conformational interconversions during the cooling process. The next four higher-energy structures (presented in the SI section) are related to four of the observed conformations by a rotation of the free −OH group in a chain structure. The charts in Figure 4 show the interconversion barriers between each pair of conformers calculated using MP2 methods. The barriers for I2(g−g−) and for II2(g+g+) from the higher-energy conformer to the lower one are each less than 200 cm−1, while the corresponding barriers for the II2(g−g−) and I2(g+g+) conformers are about 300 cm−1. In all four pairs, relaxation of the higher-energy conformers to the lower-energy ones is likely,21 possibly decreasing the populations of the former and increasing the populations of the latter in the experiment. In all of the conformers presented here, there is more than one HB stabilizing the structure. Cooperative hydrogen bonding of this type is a consequence of the fact that both oxygen and nitrogen have lone pairs of electrons, each of which can form a HB with a hydrogen attached to an adjacent group. A similar behavior occurs on a larger scale in liquid water, as

well as in water clusters. There also is a redistribution of charge on initial HB formation.22 In the model structure X−H···Y, the acceptor atom Y transfers some electron density to the donor atom X, encouraging further HB acceptance by X and donation to Y. In water, cooperative hydrogen bonding increases the average O−H bond length and decreases the average O···O distance.23 The coexistence of both cycles and chains in DTN is a characteristic property of its energy landscape. Remarkably, the two different structural types have relatively similar energies. While the cyclic forms have more HBs, the smaller number of HBs in the chain forms is compensated for by their higher strength; chain HBs are more nearly linear and exhibit shorter HB distances and more relaxed structures. The predicted structures show longer O−H distances when the hydrogen atom is linked to a nitrogen atom in the chain, compared to the cyclic structures. Also, in DTN, the −NH2 group has more acceptor-like character than the −OH group, making the OH··· N HBs shorter than the OH···O HBs. This is shown explicitly for two conformers of glycerol and DTN in Figure 5. In the

Figure 5. Calculated HB distances (in Å) in two comparable conformations of glycerol and DTN, obtained using MP2/6-311+ +G(d,p). 7271

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chain forms, the donor HB distance from the first (O)H to the central OH is larger in glycerol than the corresponding distance in DTN, whereas the donor distance from the central OH in glycerol to the third O(H) is smaller than it is in DTN. In the cyclic forms, there are two shorter HBs and one longer one in glycerol and two longer HBs and one shorter one in DTN. Clearly, all of these effects can be traced to the amino group being a better H-bond acceptor but poorer donor than its OH counterpart. Interestingly, in both glycerol and DTN, the cycles and chains have similar energies because distortions along one coordinate can be compensated for by complementary distortions along other coordinates. The energy landscapes of DTN and glycerol are significantly different, when examined in greater detail. The two molecules have equivalent conformations, as already noted. However, their predicted relative energies are different. Calculations at the MP2/6-311++G(d,p) level give for glycerol5 a conformation similar to I2(g+g+) as the global minimum, instead of the cyclic HB network, which is the second most stable form, 148 cm−1 to higher energy. All of the lower-energy conformations in DTN have their equivalent in glycerol, spanning a larger range of energies (750 cm−1). In this range, glycerol also presents extra conformations, many of which feature only one HB. Conformations similar to this for DTN are more unstable and all lie above 700 cm−1. More surprising is that glycerol has an additional conformation with respect to DTN, with an interaction (−OH)β···(−OH)γ···(−OH)α [(βγα) chain] lying at only 248 cm−1 above the global minimum, in which the central −OH group only acts as a H-donor in a HB chain. The absence of this kind of HB network in DTN provides further evidence for the stronger character of the amino group as a Hbond acceptor. DTN shares the same backbone structure with the amino acid L-threonine (THR), apart from the acid group in the α position. Calculations of the energy landscape of THR (at the MP2/6-311++G(d,p) level)24 revealed 10 conformers with energies up to 1000 cm−1 above the global minimum. Of these, the ones denoted as IIa, IIIαa, and III′αb share a similar structure with conformers I2(g+g+), II2(g+g+), and II2(g−g−), respectively, of DTN. Only the first two were observed in the pure rotational spectrum of THR; the third one was considered too high in energy (calculated at ∼700 cm−1) to be observed in the free-jet expansion. All three corresponding conformers of DTN have been detected in the present work. It is interesting that the range of energies spanned by the conformers of THR is much larger than that in DTN. Likely, this is a consequence of the additional CO group of the amino acid, a source of additional stabilization via the HBs that may be formed with it. Finally, we return to the main theme in this work, a search for possible similarities in the structural and/or dynamical properties of apparently dissimilar molecules like glycerol, DTN, and the riboses that might explain their common ability to act as scaffolds for building nucleic acids. One factor that might play a role is that all such molecules contain two or more adjacent hydroxyl and/or amino groups that can form networks of intramolecular OH···OH··· or OH···NH2··· HBs. As a result, one side of the carbon framework is electron-rich and the other is electron-poor. This is illustrated for the specific cases of the two DTN structures shown in Figure 6. Thus, establishment of cooperative HB networks leaves “exposed” two sides of the molecule, an electron-rich area to which electropositive groups might be attracted and an electron-poor area to which electronegative groups (such as phosphates and the nitro-

Figure 6. HOMOs of the two most stable predicted conformers of DTN. The molecular orbitals are located mostly above the plane of the backbone.

genous bases) might be attracted. A second factor is that such molecules exhibit many different cyclic and chain structures with nearly equivalent energies. Despite the enhanced strength of the individual HBs, they are cooperative in nature, so that strengthening one weakens another. As noted by Scheiner25 and others,26 perturbations induced by the formation of one HB are themselves affected by the presence of other HBs. A third and final factor, possibly the deciding one, is that interconversions between the different structures are relatively facile. Breaking a single HB in an isolated molecule typically requires a large energy, 1000 cm−1 or more. However, in systems where there is a cooperative HB network, the interconversion energies may be significantly smaller, 300 cm−1 or less, because the breaking of one HB is accompanied by the formation of another. (kT ≈ 200 cm−1 at room temperature for a single molecule.) Indeed, in glycerol, a multistep interconversion pathway between a OH···OH···OH chain pointing in one direction and one in the other along the chain was calculated to have a barrier in this range.5b We have not explored these pathways in detail in this work, but the calculations shown in Figure 4 provide some hint that a similar facile pathway may be present in DTN, although those interconversions do not involve breaking H-bonds but only a reorientation of the acceptor OH group. It would be interesting to calculate a more complete potential energy landscape including the various interconversion pathways in DTN compared to glycerol. Thus, DTN and other related molecules are anticipated to have relatively flat energy landscapes, which likely accounts for their versatile behavior in biological systems.

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ASSOCIATED CONTENT

* Supporting Information S

Structures of the seven next-higher-energy conformations of Dthreoninol and Tables S1−S7, showing the observed frequencies and errors for the quadrupole hyperfine components for conformers A through G of D-threoninol. Complete author list for ref 10. This material is available free of charge via the Internet at http://pubs.acs.org.

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AUTHOR INFORMATION

Corresponding Authors

*E-mail: [email protected] (D.W.P.). *E-mail: [email protected] (T.S.Z.). Author Contributions

The manuscript was written through contributions of all authors. All authors have given approval to the final version of the manuscript. Notes

The authors declare no competing financial interest. 7272

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Biologically Relevant Molecules. Phys. Chem. Chem. Phys. 2011, 13, 7253−7262. (21) Ruoff, R. S.; Klots, T. D.; Emilsson, T.; Gutowsky, H. S. Relaxation of Conformers and Isomers in Seeded Supersonic Jets of Inert Gases. J. Chem. Phys. 1990, 93, 3142−3150. (22) Scheiner, S. Hydrogen Bonding: A Theoretical Perspective; Oxford University Press: New York, 1997. (23) (a) Ludwig, R. The Effect of Hydrogen Bonding on the Thermodynamic and Spectroscopic Properties of Molecular Clusters and Liquids. Phys. Chem. Chem. Phys. 2002, 4, 5481−5487. (b) Pérez, C.; Lobsiger, S.; Seifert, N. A.; Zaleski, D. P.; Temelso, B.; Shields, G. C.; Kisiel, Z.; Pate, B. H. Broadband Fourier Transform Rotational Spectroscopy for Structure Determination: The Water Heptamer. Chem. Phys. Lett. 2013, 571, 1−15. (24) Alonso, J. L.; Perez, C.; Sanz, M. E.; Lopez, J. C.; Blanco, S. Seven Conformers of L-Threonine in the Gas Phase: A LA-MBFTMW Study. Phys. Chem. Chem. Phys. 2009, 11, 617−627. (25) Scheiner, S. Cooperativity of Multiple H-Bonds in Influencing Structural and Spectroscopic Features of the Peptide Unit of Proteins. J. Mol. Struct. 2010, 976, 49−55. (26) Parra, R. D.; Streu, K. Hydrogen Bond Cooperativity in Polyols: A DFT and AIM Study. Comput. Theor. Chem. 2011, 967, 12−18.

ACKNOWLEDGMENTS Support for this work by the National Science Foundation is gratefully acknowledged [CHE-1346608 (D.W.P.) and CHE1213289 (T.S.Z.)].

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