William Klemperer was one of the most important and creative experimental physical chemists of the second half of the twentieth century. With his invention of Molecular Beam Electric Resonance (MBER) spectroscopy coupled with supersonic expansion and a “universal detector”, the era of high resolution rotational spectroscopy of weakly-bound van der Waals and hydrogen bonded complexes began in the early 70's. The speaker was there at the creation.

William Klemperer and his research group, using Molecular Beam Electric Resonance (MBER) spectroscopy, studied a plethora of weakly bound complexes until and beyond his retirement from teaching at Harvard at age seventy-five in 2002. Many of Klemperer’s research students and postdoctoral associates went on to prolific careers of their own. Bill’s last public seminar was presented in 2013 and his last publication on weakly bound complexes appeared in 2015 at age eighty-eight.

Chemical reactions of transition metal complexes can provide precise stereocontrol of the products. A recent development in the Harman lab at the University of Virginia has demonstrated full control of the stereochemistry in the deuteration of benzene to cyclohexene using a benzene-tungsten metal complex. Complete stereocontrol of the deuteration is important in the development of deuterium substituted active pharmaceutical ingredients that offer improved safety through reduced metabolism. The goal of this project is to quantify any regioisomer and enantiomer impurities in one of the possible reaction products, 3-d-cyclohexene, after it has been removed from the metal and functionalized as cyclohexene oxide. Regioisomers can be identified using molecular rotational spectroscopy by simple analysis of the rotational spectrum of cyclohexene oxide. To validate that quantum chemistry provides a structure of cyclohexene oxide with sufficient accuracy to unambiguously identify all ten possible singly-deuterated isomers, these regioisomers have been identified in natural abundance in a broadband rotational spectrum (6-18 GHz) and the rotational constants compared to theoretical predictions. The more challenging analysis is the determination of the enantiomeric excess of the deuteration chemistry. The chiral tagging method is proposed for this analysis and two candidate tag molecules, propylene oxide (PO) and trifluoropropylene oxide (TFPO), have been evaluated for use in this application. Although chiral tag complexes are formed with both tags, TFPO offers two important advantages over PO. First, the signal levels for the chiral tag complex with TFPO are about a factor of four stronger – a major advantage since there is a limited amount of reaction product for testing (100 mg). Second, tagging with TFPO leads to cooling of the two ring pucker isomers of deuterated cyclohexene oxide and this simplifies the analysis of the enantiomeric composition of the sample.

An efficient synthesis of formamidinium formate is described. The experimental x-ray structure shows both internal and external H-bonding to surrounding molecules. However, in the gas phase, this compound occurs as a doubly hydrogen bonded dimer. This doubly hydrogen-bonded structure is quite different from the solid state structure. Microwave spectra were measured in the 6-14 GHz range using a pulsed-beam Fourier transform microwave (MW) spectrometer. The two nonequivalent N-atoms exhibit distinct quadrupole coupling. The rotational, centrifugal distortion, and quadrupole coupling constants determined from the spectra have the following values: A=5880.05(2), B=2148.7710(2), C=1575.23473(13), 1.5χaa (N1)=1.715(3), 0.5(χbb-χcc) (N1)=-1.333(4), 1.5χaa (N2)=0.381(2), 0.5(χbb-χcc) (N2)= -0.0342(2), and D_J=0.002145(5) MHz. The experimental inertial defect, ∆=-0.243amu Ų, is consistent with a planar structure. Accurate and precise rotational constants (A, B and C), obtained from the MW measurements, were closely reproduced, within 1%-2% of the measured values, with the M11 DFT functional theoretical calculations. Detailed comparison of the measured and calculated A, B, and C rotational constants confirms the planar doubly hydrogen bonded structure. The calculated nitrogen quadrupole coupling strengths of the monomer are quite different from either of the two nitrogen sites of the dimer. The poor agreement between measured and calculated quadrupole coupling strengths shows that the dimer is not locked in the equilibrium structure but is likely undergoing large amplitude vibrational motion of the hydrogen atoms moving between the N and O atoms involved in the hydrogen bonding.

1,2-Ethanediol has been shown by FTIR and Raman spectroscopy in supersonic jets to dimerize preferentially in an S₄-symmetric structure with a cyclic pattern of four strained hydrogen bondsF. Kollipost, K. E. Otto, M. A. Suhm, Angew. Chem. 2016, 128, 4667. This forces the two monomers into a heterochiral OCCO helicity. The equally frequent homochiral encounters lead to a rich variety of nearly isoenergetic, but much less stable chain topologies with only three hydrogen bonds. The latter had remained elusive in a previous study but^a are now identified and energetically modulated by chemically freezing the OCCO helicity of the monomers. This is achieved by moving to cyclic diols of different ring sizes. They are explored computationally and in several cases also spectroscopically, exploiting the established complementarities between Raman and IR spectroscopy for hydrogen bonded systemsThomas Forsting, Hannes C. Gottschalk, Beppo Hartwig, Michel Mons, Martin A. Suhm, PCCP, 2017, 19, 10727

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Footnotes:

F. Kollipost, K. E. Otto, M. A. Suhm, Angew. Chem. 2016, 128, 4667.. Thomas Forsting, Hannes C. Gottschalk, Beppo Hartwig, Michel Mons, Martin A. Suhm, PCCP, 2017, 19, 10727.

The rotational spectrum of the water adduct of tetrafluoro-1,3-dithietane has been investigated by using high resolution rotational spectroscopy. Experimental evidence and quantum theoretical analyses revealed that the two moieties are linked together through a dominant S-O chalcogen bond. The rotational transitions of four isotopologues are split into two component lines due to the internal rotation of the water moiety around its C₂ axis. In the HDO isotopologue, a small μ_c dipole moment component is generated which inverts upon water internal rotation, allowing the experimental determination of the tunneling splitting (21.46(5) GHz). Flexible model calculations can reproduce this splitting when the barrier to water internal rotation is 87.4(2) cm⁻¹.

Ground-state rotational spectra were observed for a complex of ammonia and carbon disulphide in the 2.0-18.0 GHz frequency range by Chirped Pulse Fourier Transform Microwave Spectroscopy. The complex was generated through supersonic expansion of a dilute mixture of NH₃ (1%) and CS₂ (1%) in argon. Ten symmetric-top and four asymmetric-top isotoplogues of H₃N^...CS₂ were isolated while using samples either in natural isotopic abundance or with isotopically enriched 15NH₃ or ND₃. The complex has C_3v symmetry, with the connectivity of the atoms being H₃N^...S=C=S, thereby establishing that the non-covalent interaction is a chalcogen bond involving the non-bonding electron pair of NH₃ as the nucleophile and the axial region of one of the S atoms of CS₂ as the electrophile. It is assumed that the subunit geometries are unchanged upon complex formation which is consistent with small values determined for the intermolecular force constant (kσ). A simple model was used to account for the contribution of the subunit angular oscillations to the zero-point motions and thus obtain the intermolecular bond length, r(N^... S).

Experiments performed to observe the broadband microwave spectra of 1-methylimidazole, 2-methylimidazole, 4-methylimidazole and 5-methylimidazole also yielded the spectra of molecular complexes containing these molecules. The complexes were generated through laser vaporisation of a solid target rod in the presence of a gas sample undergoing supersonic expansion and containing Ar and H₂O precursors. Spectra have thus been recorded for a series of structural isomers of Ar…C₅H₇N₂ and H₂O…C₅H₇N₂ where C₅H₇N₂ is an isomer of methylimidazole. Rotational constants, B₀, centrifugal distortion constants, D_J, and nuclear quadrupole coupling constants, χ_aa(N) and χ_bb(N)-χ_cc(N) have been determined through assignment of the observed rotational spectra. For each of the structural isomers identified, it will be shown that the argon atom of Ar…C₅H₇N₂ coordinates to π electrons of the aromatic ring of methylimidazole. The water molecule in H₂O…C₅H₇N₂ binds to the pyridinic nitrogen atom of the methylimidazole sub-unit. For each complex, the barrier to internal rotation, V₃, of the methyl group has been determined.

Perillyl alcohol (PA) is a naturally occurring dietary monoterpene that can be extracted from various plants, such as lavender and peppermint, and its application to human cancer treatment has been explored.¹ The rotational spectrum of PA has been investigated using a chirped-pulse Fourier transform microwave (FTMW) spectrometer and a cavity FTMW spectrometer. In parallel, we have carried out extensive conformational searches by scanning relevant dihedral angles and also using a semi-classical conformational search program, GFN-xTB.² In total, 108 conformers have been identified and confirmed to be true minima with the subsequent DFT calculations. The relative stabilities of the conformers identified and the interconversion barriers among them have been explored at the MP2/6-311++G(2d,p) and B3LYP-D3(BJ)/def2-TZVP levels of theory. Experimentally, 8 conformers have been assigned and the missing low energy conformers have been rationalized in terms of conformational conversion barriers under a jet expansion condition. A comprehensive study on the conformational distribution of PA may facilitate our understanding of its structural property and possible structural-functional relationship. 1 T. C. Chen, C. O Da Fonseca, A. H Schönthal. Am. J. Cancer Res. 2015, 5, 1580. 2. S. Grimme, C. Bannwarth, P. Shushkov, J. Chem. Theo. Comput. 2017, 13, 1989.

One major challenge in analytical chemistry is the quantitative determination of the ratio of all stereoisomers in a molecule with multiple chiral centers. The analysis is especially challenging if there are no reference samples available for calibration. In general, a molecule with N chiral centers has 2^N stereoisomers. There are 2N-1 distinct structures, the diastereomers, that can be distinguished by traditional rotational spectroscopy. Each diastereomer exists in two non-superimposable mirror images – the enantiomers. Menthone is a simple case of a molecule with two asymmetric carbons. The two diastereomers are known as menthone and isomenthone and each is chiral. The full analysis of the stereoisomers of several commercial samples has been performed using chirped-pulse Fourier transform microwave spectroscopy (CP-FTMW). To determine the diastereomer ratio it is necessary to determine all conformers of the molecule with appreciable population in the pulsed jet sample. The present work expands on previous efforts to assign the lowest conformers of the menthone and isomenthone by analyzing two additional conformers of isomenthone.[1] For a commercial sample where the diastereomer ratio was reported in the Certificate of Analysis, we obtained a menthone and isomenthone composition of 82.8+/-0.9 [1] Schmitz, D.; Shubert, V.A.; Betz, T.; Schnell, M., “Exploring the conformational landscape of menthol, menthone, and isomenthone: a microwave study”, Frontiers in Chemistry 3, 1-13 (2015). [2] Shubert, V.A., Schmitz, D, Schnell, M., “Enantiomer-sensitive spectroscopy and mixture analysis of chiral molecules containing two stereogenic centers – Microwave three-wave mixing of menthone”, J. Mol. Spectrosc. 300, 31-36 (2014).