Thomas Hellman Morton

Chelation of a proton by an aliphatic tertiary diamine.

A series of monoprotonated aliphatic diamines has been examined, which crystallize in three general motifs: salt-bridged, cyclic, or clustered. The monoprotonated triflic acid salt of Me2N(CH2)4NMe2 forms a proton-bridged cyclic cation. The internal N-N distance is 2.66 A, with the bridging proton in the middle, having an NHN angle >/=172 degrees. The triflate oxygens lie more than 4 A away from the midpoint between the nitrogen atoms, indicating that a salt bridge does not form. The average NH distance in a solid sample was determined by measuring the 15N-H dipolar coupling in the triflic acid salt of the completely deuterated diamine (CD3)2N(CD2)4N(CD3)2. The value of the dipolar coupling constant, 5250 +/- 90 Hz, corresponds to an average NH distance of 1.32 A, nearly half-the NN distance. That result agrees with DFT calculations, which give a double-well potential minimum for proton transit between the two amino groups, having a zero-point vibrational level close to the barrier top. Theory predicts that the maximum value of the zero point vibrational wave function is almost coincident with a local potential energy maximum, consistent with the experimental findings.

Structure, Vibrational Spectra, and Unimolecular Dissociation of Gaseous 1-Fluoro-1-phenethyl Cations

The multiple CF bond character of PhCFMe (+) ions has been examined by means of theory, vibrational spectroscopy of the gaseous ions, and unimolecular decomposition chemistry. Atoms in Molecules analysis of DFT wave functions gives a CF bond order of n = 1.25 (as compared with n = 1.38 for Me 2CF (+), relative to n = 1 for fluoromethane and n = 2 for diatomic CF (+)), which is consistent with calculations of adiabatic CF stretching frequencies (nu CF). Experimental gas phase IR spectra, recorded by means of resonant multiphoton dissociation (IRMPD) using a free-electron laser connected to an FTICR mass spectrometer, show good agreement with predicted band positions for five deuterated isotopomers of PhCFMe (+). Metastable ion decompositions of deuterated analogues of PhCFMe (+) show the same HF/DF loss patterns as those produced by IRMPD. The evidence supports the conclusion that PhCFMe ions retain structural integrity until they become sufficiently excited to dissociate, whereupon they undergo intramolecular hydrogen scrambling that is competitive with HF/DF expulsion. Relative rates of hydrogen transposition and unimolecular dissociation are extracted from relative experimental fragment ion abundances. The predominant decomposition pathway is inferred to operate via a five-center transition state, as opposed to a four-center transition state for HF loss from gaseous Me 2CF (+).

Fast and loose covalent binding of ketones as a molecular mechanism in vertebrate olfactory receptors: Chemical production of selective anosmia

Abstract Olfactory receptors undoubtedly have fast rates of association with odorant molecules. If the dissociation rate is also fast, the dissociation constant, Kd, will be comparatively large (≥10-6M). With such fast and loose binding, a receptor will recover function rapidly. If, on the other hand, the dissociation rate is slow, odorant binding will be tight, and the receptor will have slow recorvery. Previous investigators have explored tight binding (Kd≤10-8M). The present study is the first to probe the possibility of fast and loose binding in the olfactory epithelium of air-breathing vertebrates. Our approach is based on the conjecture that ketones are bound as Schiff bases (just as retinal is bound in visual pigment). As a model system, the Schiff base-forming bacterial enzyme acetoacetate decarboxylase (AAD) has been studied. Nucleophilic attack (e.g. BH4- reduction) of reversible AAD-carbonyl complexes produces irreversible binding to the active site in a fraction, φ, of the enzyme molecules. Kinetics are discussed and interpreted using the derived expression φ=1-[Kd/(Kd+S0)]m, where S0 is the initial concentration of carbonyl substrate and the exponent m is the ratio of the rate constant for attack of the protein-substrate complex to the rate constant for removal of substrate (e.g. by hypothesize attack of the free carbonyl). We hypothesize a similar pathway when the olfactory epithelium of experimental animals is treated with solutions of cyclohexanone or ethyl acetoacetate, in which Schiff base linkages are attacked in vivo by some endogenous nucleophile. We have developed a behavioral assay for olfactory receptor inactivation and report the first example of a chemically produced selective anosmia (odor blindness).

A Gas chromatographic (GLPC) model for the sense of smell. Variation of olfactory sensitivity with conditions of stimulation

Abstract Computer simulation of an olfactory detector has been developed using a chemical kinetic scheme originally proposed by McNab and Koshland for bacterial chemotaxis. This model describes response as a function of two opposed reactions, both of which are activated by odorant. One reaction turns on response, while its opponent shuts it off. Net response to various stimulus profiles is compared to psychophysical experiments, with particular attention paid to simulating magnitude estimation and odor adaptation results. Effects of the access route to this detector are evaluated. Transport of odorant molecules is treated as having two sequential steps: step (i), airborne odorant is carried parallel to a retentive layer (mucus) into the detector region; step (ii), molecules diffuse through the retentive layer to the detector. Step (i) is represented as analogous to GLPC on an open tubular column. Each step has a characteristic time constant, which is proportional to (distance)2/diffusion coefficient. Response to highly volatile odorants tends to be limited by step (ii), while odorants of low volatility approach the step (i) limit. Sensitivity at both limits is attenuated by increasing the thickness of the retentive layer, but sensitivity at the step (i) limit is also affected by changes in air passageway and airflow characteristics. This picture can be used to explain variations in womens sensitivity to odorants of low volatility with the menstrual cycle, while their detection of volatile odorants fluctuates to a much lesser extent.

Photoionization of methyl t-butyl ether (MTBE) and t-octyl methyl ether (TOME) and analysis of their pyrolyses by supersonic jet/photoionization mass spectrometry☆

Abstract The pyrolysis products of neutral methyl- d 3 t -butyl ether (MTBE- d 3 ), its undeuterated analogue, and t -octyl methyl ether (TOME) have been analyzed by means of supersonic jet expansion followed by 118 nm photoionization/time-of-flight mass spectrometry. The mass spectra recorded for pyrolysis temperatures up to 1200 °C are compared with the photoionization efficiency (PIE) of room temperature samples as a function of photon energy in the domain 9–13 eV. Differences in fragment ion abundances measured by the two techniques permit the dissection of ion decomposition profiles away from thermal cracking patterns. MTBE and TOME both exhibit base peaks at m/z 73 (which shifts to m/z 76 for MTBE- d 3 ). For neutral MTBE at room temperature, supersonic expansion followed by 118 nm photoionization of the jet-cooled molecular beam gives a mass spectrum in which the molecular ion appears with approximately 10% the abundance of the base peak, a much higher relative intensity than is seen for the molecular ion at any wavelength when the neutral precursor is photoionized at room temperature. Pyrolysis of MTBE leads to molecular elimination of methanol as the only observed thermal decomposition (in agreement with previous studies) up to roughly 1000 °C. At temperatures ≥1050 °C, however, detectable levels of bond homolysis take place, as revealed by the production of both CH 3 · and CD 3 · (observed as m/z 15 and 18 in the photoionization mass spectra) from (CH 3 ) 3 COCD 3 . This result is consistent with the expectation that bond homolysis should have an Arrhenius preexponential factor >100 times greater than that for molecular elimination, which compensates for the 0.9 eV higher energy barrier difference at sufficiently elevated temperatures. TOME also displays molecular elimination, but the prevalence of homolysis in the resulting alkenes (2,4,4-trimethylpentenes) prevents assessment of direct bond homolysis in TOME.

SMALL ODORANT MOLECULES AFFECT STEADY STATE PROPERTIES OF MONOLAYERS

Abstract Interactions of organic compounds with polar lipid monolayers have been widely studied and fall into two general categories: polar molecules (often electrically charged), which interact primarily with head groups, and non-polar molecules, which interact with tail groups. This study presents results for a typical odorant molecule, cyclohexanone, which is semipolar in the sense that the dipolar functional group (a carbonyl) is part of a small, non-polar hydrocarbon ring. Thermodynamic measurements on monolayers prepared from pure L-α- dipalmitoyllecithin (DPPC) reveal effects from cyclohexanone in the subphase on the ΔG for compression, which exhibits a maximum as a function of temperature, suggesting that interaction of the cyclohexane ring with hydrophobic tail groups dominates below 297 K, while interaction of the carbonyl function with head groups dominates above 297 K. Measurements of the surface dipole moment confirm this inference: when cyclohexanone is in the subphase the surface dipole moment is less than the value of μ for pure DPPC when the temperature is below 297 K. Above 297 K the surface dipole moment in the presence of cyclohexanone has a value greater than or equal to μ for pure DPPC. Variations in orientation of small molecules within lipid assemblies might conceivably contribute to membrane recognition of an odorant.

Proton-Bridge Motions in Amine Conjugate Acid Ions Having Intramolecular Hydrogen Bonds to Hydroxyl and Amine Groups

Vibrational spectra of two gaseous cations having NH···O intramolecular ionic hydrogen bonds and of nine protonated di- and polyamines having NH···N internal proton bridges, recorded using IR Multiple Photon Dissociation (IRMPD) of mass-selected ions, are reported. The band positions of hydroxyl stretching frequencies do not shift when a protonated amine becomes hydrogen bonded to oxygen. In three protonated diamines, lower frequency bands (550-650 cm(-1)) disappear upon isotopic substitution, as well as several bands in the 1100-1350 cm(-1) region. By treating the internal proton bridge as a linear triatomic, theory assigns the lowest frequency bands to N-H···N asymmetric stretches. A 2-dimensional model, based on quantization on a surface fit to points calculated using a double hybrid functional B2-P3LYP/cc-pVTZ//B3LYP/6-31G**, predicts their positions accurately. In at least one case, the conjugate acid of 1,5-cis-bis(dimethylamino)cyclooctane, a N-H···N bend shows up in the domain predicted by DFT normal mode calculations, but in most other cases the observed bands have frequencies 20-25% lower than expected for bending vibrations. Protonated Me(2)NCH(2)CMe(2)CH(2)CH(2)CH(2)NMe(2) shows three well-resolved bands at 620, 1200, and 1320 cm(-1), of which the lowest can be assigned to the asymmetric stretch. Other ions observed include doubly protonated 1,2,4,5-(Me(2)NCH(2))(4)-benzene and 1,2,4-(Me(2)NCH(2))(3)-benzene-5-CH(2)OH. Apart from the aforementioned rigid ion derived from the alicyclic diamine, the other ions enjoy greater conformational mobility, and coupling to low-frequency C-C bond torsions may account for the shift of vibrations with N-H···N character to lower frequencies. Low-barrier hydrogen bonding (LBHB) accounts for the fact that N-H···N asymmetric stretching vibrations of near linear proton bridges occur at frequencies below 650 cm(-1).

The cationic C==F+ stretching vibration in the gas phase.

The carbonyl stretch has been recognized as the most distinctive vibration of polyatomic organic molecules, after Coblentz reported the infrared (IR) absorptions of aromatic aldehydes more than a century ago. The present work explores the comparison between the C=O and C=F bonds, which are isoelectronic and isolobal. Theory predicts that direct attachment of halogen (X) to a positively charged sp carbon leads to CX bonding with lone-pair back donation, which is tighter than a single bond. IR spectroscopy has shown back donation for a-chlorocarbocations. Natural bond orbital (NBO) analysis predicts that the cationic C F bond possesses an even higher degree of p character than the cationic C Cl bond, and is appropriately represented as C=F in the absence of additional conjugative stabilization. Because carbocations are highly reactive, preparing them in media compatible with IR spectroscopy has demanded considerable ingenuity. For this reason, determining IR absorptions of gaseous ions by means of their subsequent dissociation is a new and growing field. The wavelength dependence of resonant IR multiphoton dissociation (IRMPD) of gaseous ions, as measured with a Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometer, reveals their vibrational spectra. To induce IRMPD, experiments described herein make use of the free electron laser FELIX as a source of intense and conveniently tunable IR radiation. These measurements confirm the partial double bond between electron-deficient carbon and fluorine atoms. Dopfer and co-workers have examined resonant IRMPD spectra of protonated fluorobenzene. One of the isomers has a partial positive charge on the carbon to which fluorine is attached, as depicted by resonance structure 1. These investigators correlated two in-plane vibrations of neutral fluorobenzene that have a high degree of C F stretching character (ñ7a = 1239 cm 1 and ñ8a = 1603 cm ) with bands observed for 1 at 1308 and 1583 cm . Coupling with other motions makes it difficult to assess more precisely how much the stiffness of the C F bond in the cation differs from that of the neutral molecule. More recently, Reed and co-workers have reported IR absorption spectra of crystalline salts of ions 2 and 3. The reported bands for the cationic C F stretch occur at 1175 and 1154 cm . Theory predicts that the C=F stretch in more highly saturated systems should occur at higher frequencies. Among the simplest ions of this nature, the 2-fluoroisopropyl cation (4), was prepared in solution by Olah and coworkers, but its vibrational spectra have not been published. This same ion has been created in the gas phase by Eyler, Lias, and Ausloos by the reaction of CF3 + ion with acetone, in which CF2O is the uncharged byproduct. [10] Equation (1) illustrates this metathesis reaction schematically. The structure of ion 4 in the gas phase has been confirmed by collection and identification of the neutral products from its subsequent ion–molecule reactions.

Proton-bound dimers of 1-methylcytosine and its derivatives: vibrational and NMR spectroscopy

Vibrational spectroscopy and NMR demonstrate that the proton-bound dimer of 1-methylcytosine, 1, has an unsymmetrical structure at room temperature. In the gas phase, investigation of isolated homodimer 1 reveals five fundamental NH vibrations by IR Multiple Photon Dissociation (IRMPD) action spectroscopy. The NH···N stretching vibration between the two ring nitrogens exhibits a frequency of 1570 cm(-1), as confirmed by examination of the proton-bound homodimers of 5-fluoro-1-methycytosine, 2, and of 1,5-dimethylcytosine, 3, which display absorptions in the same region that disappear upon deuterium substitution. (13)C, and (15)N NMR of the solid iodide salt of 1 confirm the nonequivalence of the two rings in the anhydrous proton-bound homodimer at room temperature. IRMPD spectra of the three possible heterodimers also show NH···N stretches in the same domain, and at least one of the heterodimers, the proton-bound dimer of 1,5-dimethylcytosine with 1-methylcytosine, exhibits two bands suggestive of the presence of two tautomers close in energy.

IR Spectra of Boron-Stabilized Anions in the Gas Phase

Action spectroscopy of gaseous Me(3)BF(-) and Me(2)BCH(2)(-), determined using IR multiple photon dissociation (IRMPD), exhibits experimental peak positions in good agreement with those predicted by anharmonic DFT calculations at the B3LYP/aug-cc-pVTZ level. Comparing spring constants among boron-carbon bonds and consideration of isoelectronic systems reveals that the anions have B-CH(3) bonds a factor of 1.3-1.4 weaker than those in neutral trimethylboron, suggesting a greater role for hyperconjugation in B(CH(3))(3) than inferred from previous vibrational spectroscopic studies.