Binding Water Clusters to an Aromatic-Rich Hydrophobic Pocket: [2.2.2]Paracyclophane–(H₂O)_<i>n</i>, <i>n</i> = 1–5

[2.2.2]­Paracylcophane (tricyclophane, TCP) is a macrocycle with three phenyl substituents linked by ethyl bridges (−CH₂CH₂−) in the para-position, forming an aromatic-rich pocket capable of binding various substituents, including nature’s solvent, water. Building on previous work [Buchanan, E. G.; et al. <i>J. Chem. Phys.</i> <b>2013</b>, <i>138</i>, 064308] that reported on the ground state conformational preferences of TCP, the focus of the present study is on the infrared and ultraviolet spectroscopy of TCP–(H₂O)_<i>n</i> clusters with <i>n</i> = 1–5. Resonant two-photon ionization (R2PI) was used to interrogate the mass selected electronic spectrum of the clusters, reporting on the perturbations imposed on the electronic states of TCP as the size of the water clusters bound to it vary in size from <i>n</i> = 1–5. The TCP–(H₂O)_<i>n</i> S₀–S₁ origins are shifted to lower frequency from the monomer, indicating an increased binding energy of the water or water network in the excited state. Ground state resonant ion-dip infrared (RIDIR) spectra of TCP–(H₂O)_<i>n</i> (<i>n</i> = 1–5) clusters were recorded in the OH stretch region, which probes the H-bonded water networks present and the perturbations imposed on them by TCP. The experimental frequencies are compared with harmonic vibrational frequencies calculated using density functional theory (DFT) with the dispersion-corrected functional ωB97X-D and a 6-311+g­(d,p) basis set, providing firm assignments for their H-bonding structures. The H₂O molecule in TCP–(H₂O)₁ sits on top of the binding pocket, donating both of its hydrogen atoms to the aromatic-rich interior of the monomer. The antisymmetric stretch fundamental of H₂O in the complex is composed of a closely spaced set of transitions that likely reflect contributions from both para- and ortho-forms of H₂O due to internal rotation of the H₂O in the binding pocket. TCP–(H₂O)₂ also exists in a single conformational isomer that retains the same double-donor binding motif for the first water molecule, with the second H₂O acting as a donor to the first, thereby forming a water dimer. The OH stretch infrared spectrum reflects a cooperative strengthening of both π-bound and OH···O H-bonds due to binding to TCP. The TCP–(H₂O)_<i>n</i>, <i>n</i> = 3–5 clusters all form H-bonded cycles, retaining their preferred structures in the absence of TCP, but distorted significantly by the presence of the TCP molecule. TCP–(H₂O)₃ divides its population between two conformational isomers that differ in the direction of the H-bonds in the cycle, either clockwise or counterclockwise, which are distinguishable by virtue of the <i>C</i>₂ symmetry of the TCP monomer. TCP–(H₂O)₄ and TCP–(H₂O)₅ have OH stretch IR spectra that are close analogues of their benzene–(H₂O)_<i>n</i> counterparts in the H-bonded OH stretch region, but differ somewhat in the free and π OH stretch regions as the tetramer and pentamer cycles begin to spill out of the pocket interior. Lastly, excited state RIDIR spectroscopy in the OH stretch region is used to probe the response of water cluster to ultraviolet excitation, showing how the proximity of a given water molecule to the aromatic-rich π clouds affects the infrared spectrum of the water network

Broadband Microwave Spectroscopy of Prototypical Amino Alcohols and Polyamines: Competition between H‑Bonded Cycles and Chains

The rotational spectra of the amino alcohols d-allo-threoninol, 2-amino-1,3-propanediol, and 1,3-diamino-2-propanol and the triamine analog, propane-1,2,3-triamine, have been investigated under jet-cooled conditions over the 7.5–18.5 GHz frequency range using chirped-pulsed Fourier transform microwave spectroscopy. Microwave transitions due to three conformers of d-allothreoninol, four conformers of 2-amino-1,3-propanediol, four conformers of 1,3-diamino-2-propanol, and four conformers of propane-1,2,3-triamine have been identified and assigned, aided by comparison of the fitted experimental rotational constants with the predictions for candidate structures based on an exhaustive conformational search using force field, <i>ab initio</i> and DFT methods. Distinctions between conformers with similar rotational constants were made on the basis of the observed nuclear quadrupole splittings and relative line strengths, which reflect the direction of the permanent dipole moment of the conformers. With three adjacent H-bonding substituents along the alkyl chain involving a combination of OH and NH₂ groups, hydrogen-bonded cycles (3 H-bonds) and chains (2 H-bonds) remain close in energy, no matter what the OH/NH₂ composition. Two families of H-bonded chains are possible, with H-bonding substituents forming curved chain or extended chain structures. Percent populations of the observed conformers were extracted from the relative intensities of their microwave spectra, which compare favorably with relative energies calculated at the B2PLYP-D3BJ/aug-cc-pVTZ level of theory. In glycerol (3 OH), d-allothreoninol (2 OH, 1 NH₂), 2-amino-1,3-propanediol (2 OH, 1 NH₂), and 1,3-diamino-2-propanol (1 OH, 2 NH₂), H-bonded cycles are most highly populated, followed by curved chains (3 OH or 2 OH/1 NH₂) or extended chains (1 OH/2 NH₂). In propane-1,2,3-triamine (3 NH₂), H-bonded cycles are pushed higher in energy than both curved and extended chains, which carry all the observed population. The NH₂ group serves as a better H-bond acceptor than donor, as is evidenced by optimized structures in which H-bond lengths fall into the following order: <i>r</i>(OH···N) ≈ <i>r</i>(OH···O) < <i>r</i>(NH···N) ≈ <i>r</i>(NH···O)

Solvent Effects on Vibronic Coupling in a Flexible Bichromophore: Electronic Localization and Energy Transfer induced by a Single Water Molecule

Size and conformation-specific ultraviolet and infrared spectra are used to probe the effects of binding a single water molecule on the close-lying excited states present in a model flexible bichromophore, 1,2-diphenoxyethane (DPOE). The water molecule binds to DPOE asymmetrically, thereby localizing the two electronically excited states on one or the other ring, producing a S₁/S₂ splitting of 190 cm^–1. Electronic localization is reflected clearly in the OH stretch transitions in the excited states. Since the S₂ origin is imbedded in vibronic levels of the S₁ manifold, its OH stretch spectrum reflects the vibronic coupling between these levels, producing four OH stretch transitions that are a sum of contributions from S₂-localized and S₁-localized excited states. The single solvent water molecule thus plays multiple roles, localizing the electronic excitation in the bichromophore, inducing electronic energy transfer between the two rings, and reporting on the state mixing via its OH stretch absorptions

Mixed 14/16 Helices in the Gas Phase: Conformation-Specific Spectroscopy of Z‑(Gly)_<i>n</i>, <i>n</i> = 1, 3, 5

Single-conformation ultraviolet and infrared spectroscopy has been carried out on the neutral peptide series, Z-(Gly)_<i>n</i>-OH, <i>n</i> = 1,3,5 (ZGn) and Z-(Gly)₅-NHMe (ZG5-NHMe) in the isolated environment of a supersonic expansion. The N-terminal Z-cap (carboxybenzyl) provides an ultraviolet chromophore for resonant two-photon ionization (R2PI) spectroscopy. Conformation-specific infrared spectra were recorded in double resonance using resonant ion-dip infrared spectroscopy (RIDIRS). By comparing the experimental spectra with the predictions of DFT M05-2X/6-31+G­(d) calculations, the structures could be characterized in terms of the sequence of intramolecular H-bonded rings of varying size. Despite the enhanced flexibility of the glycine residues, a total of only six conformers were observed among the four molecules. Two conformers for ZG1 were found with the major conformation taking on an extended, planar β-strand conformation. Two conformers were observed for ZG3, with the majority of the population in a C11/C7/C7/π­(<i>g</i>−) structure that forms a full loop of the glycine chain. Both ZG5 molecules had their population primarily in a single conformation, with structures characteristic of the first stages of a “mixed” β-helix. C14/C16 H-bonded rings in opposing directions (N → C and C → N) tie the helix together, with nearest-neighbor C7 rings turning the backbone so that it forms the helix. φ/ψ angles alternate in sign along the backbone, as is characteristic of the mixed, C14/C16 β-helix. The calculated conformational energies of these structures are unusually stable relative to all others, with energies significantly lower than the PGI/PGII conformations characteristic of polyglycine structures in solution and in the crystalline form, where intermolecular H-bonds play a role

Single Conformation Spectroscopy of Suberoylanilide Hydroxamic Acid: A Molecule Bites Its Tail

Suberoylanilide hydroxamic acid (SAHA) is a histone deacetylase inhibitor that causes growth arrest and differentiation of many tumor types and is an approved drug for the treatment of cancer. The chemical structure of SAHA consists of formanilide “head” and a hydroxamic acid “tail” separated by an <i>n</i>-hexyl chain, C₆H₅NH­(CO)-(CH₂)₆-(CO)­NHOH. The alkyl chain’s preference for extended structures is in competition with tail-to-head (T-H) or head-to-tail (H-T) hydrogen bonds between the amide and hydroxamic acid groups. Laser desorption was used to bring SAHA into the gas phase and cool it in a supersonic expansion before interrogation with mass-resolved resonant two-photon ionization spectroscopy. Single conformation UV spectra in the S₀-S₁ region and infrared spectra in the hydride stretch and mid-IR regions were recorded using IR-UV hole-burning and resonant ion-dip infrared spectroscopy, respectively. Three conformers of SAHA were distinguished and spectroscopically characterized. Comparison of the experimental IR spectra with the predictions of density functional theory calculations (DFT, B3LYP D3BJ/6-31+G­(d)) leads to assignments for the three conformers, all of which possess tightly folded alkyl chains that enable formation of a T-H (conformer A) or H-T (conformers B and C) hydrogen bonds. A modified version of the generalized Amber force field was developed to more accurately describe the hydroxamic acid OH internal rotor potential, leading to predictions for the relative energies in reasonable agreement with experiment. This force field was used to generate a disconnectivity graph for the low-energy portion of the potential energy landscape of SAHA. This disconnectivity graph contains more than one hundred minima and maps out the lowest-energy pathways between them, which could then be characterized via DFT calculations. This combination of force field and DFT calculations provides insight into the potential energy landscape and how population was funneled into the three observed conformers

Infrared and Electronic Spectroscopy of the Jet-Cooled 5‑Methyl-2-furanylmethyl Radical Derived from the Biofuel 2,5-Dimethylfuran

The electronic and infrared spectra of the 5-methyl-2-furanylmethyl (MFM) radical have been characterized under jet-cooled conditions in the gas phase. This resonance-stabilized radical is formed by H atom loss from one of the methyl groups of 2,5-dimethylfuran (DMF), a promising second-generation biofuel. As a resonance-stabilized radical, it plays an important role in the flame chemistry of DMF. The D₀–D₁ transition was studied using two-color resonant two-photon ionization (2C-R2PI) spectroscopy. The electronic origin is in the middle of the visible spectrum (21934 cm^–1 = 455.9 nm) and is accompanied by Franck–Condon activity involving the hindered methyl rotor. The frequencies and intensities are fit to a one-dimensional methyl rotor potential, using the calculated form of the ground state potential. The methyl rotor reports sensitively on the local electronic environment and how it changes with electronic excitation, shifting from a preferred ground state orientation with one CH in-plane and <i>anti</i> to the furan oxygen, to an orientation in the excited state in which one CH group is <i>axial</i> to the plane of the furan ring. Ground and excited state alkyl CH stretch infrared spectra are recorded using resonant ion-dip infrared (RIDIR) spectroscopy, offering a complementary view of the methyl group and its response to electronic excitation. Dramatic changes in the CH stretch transitions with electronic state reflect the changing preference for the methyl group orientation

Plant Sunscreens in the UV-B: Ultraviolet Spectroscopy of Jet-Cooled Sinapoyl Malate, Sinapic Acid, and Sinapate Ester Derivatives

Ultraviolet spectroscopy of sinapoyl malate, an essential UV-B screening agent in plants, was carried out in the cold, isolated environment of a supersonic expansion to explore its intrinsic UV spectral properties in detail. Despite these conditions, sinapoyl malate displays anomalous spectral broadening extending well over 1000 cm^–1 in the UV-B region, presenting the tantalizing prospect that nature’s selection of UV-B sunscreen is based in part on the inherent quantum mechanical features of its excited states. Jet-cooling provides an ideal setting in which to explore this topic, where complications from intermolecular interactions are eliminated. In order to better understand the structural causes of this behavior, the UV spectroscopy of a series of sinapate esters was undertaken and compared with <i>ab initio</i> calculations, starting with the simplest sinapate chromophore sinapic acid, and building up the ester side chain to sinapoyl malate. This “deconstruction” approach provided insight into the active mechanism intrinsic to sinapoyl malate, which is tentatively attributed to mixing of the bright V (¹ππ*) state with an adiabatically lower ¹nπ* state which, according to calculations, shows unique charge-transfer characteristics brought on by the electron-rich malate side chain. All members of the series absorb strongly in the UV-B region, but significant differences emerge in the appearance of the spectrum among the series, with derivatives most closely associated with sinapoyl malate showing characteristic broadening even under jet-cooled conditions. The long vibronic progressions, conformational distribution, and large oscillator strength of the V (ππ*) transition in sinapates makes them ideal candidates for their role as UV-B screening agents in plants

Vibronic Spectroscopy of a Nitrile/Isonitrile Isoelectronic Pair: <i>para</i>-Diisocyanobenzene and <i>para</i>-Isocyanobenzonitrile

The ultraviolet spectroscopy of isoelectronic pair <i>para</i>-diisocyanobenzene (<i>p</i>DIB) and <i>para</i>-isocyanobenzonitrile (<i>p</i>IBN) has been studied under gas-phase, jet-cooled conditions. These molecules complete a sequence of mono and disubstituted nitrile/isonitrile benzene derivatives, enabling a comparison of the electronic effects of such substitution. Utilizing laser-induced fluorescence (LIF) and resonant two-photon ionization (R2PI) spectroscopy, the S₀–S₁ electronic origins of <i>p</i>DIB and <i>p</i>IBN have been identified at 35 566 and 35 443 cm^–1, respectively. In <i>p</i>DIB, the S₀–S₁ origin is very weak, with b_3g fundamentals induced by vibronic coupling to the S₂ state dominating the spectrum at 501 cm^–1 (ν₁₇, isocyano bend) and 650 cm^–1 (ν₁₆, ring distortion). The spectrum extends over 5000 cm^–1, remaining sharp and relatively uncongested over much of this range. Dispersed fluorescence (DFL) spectra confirm the dominating role played by vibronic coupling and identify Franck–Condon active ring modes built off the vibronically-induced bands. In <i>p</i>DIB, the S₂ state has been tentatively observed at about 6100 cm^–1 above the S₀–S₁ origin. In <i>p</i>IBN, the S₀–S₁ origin is considerably stronger, but vibronic coupling still plays an important role, involving fundamentals of b₂ symmetry. The bending mode of the nitrile group dominates the vibronically-induced activity. Calculations carried out at the TD-DFT B3LYP/6-31+G­(d) level of theory account for the extremely weak S₀–S₁ oscillator strength of <i>p</i>DIB and the larger intensity of the S₀–S₁ origins of <i>p</i>IBN and <i>p</i>DCB (<i>para</i>-dicyanobenzene) as nitrile groups are substituted for isonitrile groups. In <i>p</i>DIB, a nearly perfect cancellation of transition dipoles occurs due to two one-electron transitions that contribute nearly equally to the S₀–S₁ transition. The spectra of both molecules show no clear evidence of charge-transfer interactions that play such an important role in some cyanobenzene derivatives

Delicate Balance of Hydrogen Bonding Forces in d‑Threoninol

The seven most stable conformers of d-threoninol (2­(<i>S</i>)-amino-1,3­(<i>S</i>)-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

Isomer-Specific Spectroscopy of Benzene–(H₂O)_<i>n</i>, <i>n</i> = 6,7: Benzene’s Role in Reshaping Water’s Three-Dimensional Networks

The water hexamer and heptamer are the smallest sized water clusters that support three-dimensional hydrogen-bonded networks, with several competing structures that could be altered by interactions with a solute. Using infrared–ultraviolet double resonance spectroscopy, we record isomer-specific OH stretch infrared spectra of gas-phase benzene-(H₂O)_6,7 clusters that demonstrate benzene’s surprising role in reshaping (H₂O)_6,7. The single observed isomer of benzene-(H₂O)₆ incorporates an inverted book structure rather than the cage or prism. The main conformer of benzene-(H₂O)₇ is an inserted-cubic structure in which benzene replaces one water molecule in the <i>S</i>₄-symmetry cube of the water octamer, inserting itself into the water cluster by engaging as a π H-bond acceptor with one water and via CH···O donor interactions with two others. The corresponding <i>D</i>_2d-symmetry inserted-cube structure is not observed, consistent with the calculated energetic preference for the <i>S</i>₄ over the <i>D</i>_2d inserted cube. A reduced-dimension model that incorporates stretch–bend Fermi resonance accounts for the spectra in detail and sheds light on the hydrogen-bonding networks themselves and on the perturbations imposed on them by benzene