Search

This Letter reports a counterintuitive observation that methylation of the glycine-iodide cluster leads to fewer conformations and spectroscopic simplicity. Cryogenic "iodide-tagging" negative ion photoelectron spectroscopy (NIPES) is used to probe specific binding sites of three N-methylated glycine derivatives, i.e., N-methylglycine (sarcosine), N,N-dimethylglycine, and N,N,N-trimethylglycine (glycine betaine). NIPES reveals a progressive spectral simplification of the iodide clusters with increasing methylation due to fewer contributing structures. Low energy conformers and tautomers of each cluster are computationally identified, and those observed in the experiments are assigned based on excellent agreement between the NIPE spectra and theoretical simulations. Zwitterionic cluster structures are found to be less stable than their canonical forms and do not contribute to the observed spectra. This work demonstrates the power of iodide-tagging NIPES in probing conformations of amino acid-iodide clusters and provides a molecular level understanding on the effect of methyl substitution on amino acid binding sites.

A series of electrostatically enhanced phosphoric acid catalysts were synthesized and studied. These compounds possess two positively charged N-octylpyridinium or triarylphosphonium ion centers at the 3,3'-positions of the (R)-BINOL backbone to enhance reactivity and provide needed steric bulk for enantioselective transformations. Catalytic activities for Friedel-Crafts alkylations of indoles with trans-β-nitrostyrenes were studied. Both types of catalysts accelerate reaction conversions relative to noncharged analogues, and good enantioselectivities up to 90% ee are observed with the phosphonium-ion-tagged phosphoric acids. This transformation also can be scaled up to synthetically useful amounts, affording >250 mg of product without losing any reactivity or selectivity.

This work showcases cryogenic and temperature-dependent "iodide-tagging" photoelectron spectroscopy to probe specific binding sites of amino acids using the glycine-iodide complex (Gly·I-) as a case study. Multiple Gly·I- isomers were generated from ambient electrospray ionization and kinetically isolated in a cryogenic ion trap. These structures were characterized with temperature-dependent "iodide-tagging" negative ion photoelectron spectroscopy (NIPES), where iodide was used as the "messenger" to interpret electronic energetics and structural information of various Gly·I- isomers. Accompanied by theoretical computations and Franck-Condon simulations, a total of five cluster structures have been identified along with their various binding motifs. This work demonstrates that "iodide-tagging" NIPES is a powerful general means for probing specific binding interactions in biological molecules of interest.

Cycloadditions of epoxides with CO2 to synthesize cyclic five-membered ring organic carbonates are of broad interest from a synthetic, environmental, and green chemistry perspective, and the development of effective catalysts for these transformations is an ongoing challenge. A series of eight charge-containing thiourea salts that catalyze these reactions under mild conditions (i.e., 60 °C and atmospheric CO2 pressure) are reported. Substrate scope and mechanistic studies were also carried out, isotope effects were measured, and a reactive intermediate was isolated revealing a surprising pathway in which a thiourea catalyst serves as a nucleophile in the cleavage of the epoxide ring.

A series of highly reactive metal-free chiral phosphoric acids possessing positively charged phosphonium ion substituents are reported and have been applied to Friedel-Crafts alkylations of indoles and 2,2,2-trifluoromethyl aryl ketones. These catalysts are orders-of-magnitude more active and have similar or better enantioselectivities than their noncharged analogues. High tolerance to a range of substrates with electron-withdrawing and electron-donating substituents was also observed.

A series of methylated and octylated pyridinium and quinolinium containing thiourea salts with a chiral 2-indanol substituent are reported. These organocatalysts are positively charged analogues of privileged bis(3,5-trifluoromethyl)phenyl substituted thioureas, and are found to be much more active catalysts despite the absence of an additional hydrogen bond donor or acceptor site (i.e., the presence of a heteroatom-hydrogen or heteroatom). Friedel-Crafts reactions of trans-β-nitorostyrenes with indoles are examined, and good yields and enantioselectivities are obtained. Mechanistic studies indicate that this is a second-order transformation under the employed conditions, and is consistent with the dimer of the thiourea being the active catalyst. Charged organocatalysts, consequently, represent an attractive design strategy for catalyst development.

Electrospray ionization of 2,6-naphthalenedicarboxylic acid readily affords its doubly deprotonated dicarboxylate dianion (12−). This species clusters with background water and added alcohols in an ion trap at ∼10−3 Torr. Sequential solvation is observed to afford mono and dicoordinated ions. Surprisingly, the latter cluster (12−• 2TFE) is protonated by 2,2,2-trifluoroethanol (TFE) whereas 12−and 12−• TFE are not even though ΔH°acid(TFE) = 361.7 ± 2.5 kcal mol−1 (as given in the NIST website at http://webbook.nist.gov) and the B3LYP/6-31+G(d,p) proton affinities are 384.7 (12−), 377.6 (12−• TFE), and 362.7 (12−• 2TFE) kcal mol−1. That is, only the weakest base in this series, and the dianion with an equal number of solvent molecules and charged sites, undergoes proton transfer. In a FTMS instrument at lower pressures (∼10−8 Torr) inefficient proton abstraction is observed with the monosolvated dianion. This difference, and the observed reactivities of 12−, 12−• TFE and 12−• 2TFE are rationalized with the aid of computed potential energy surfaces. The chemical structures of these cluster ions were also probed via collision-induced dissociations, infrared photodissociation from 2700 to 3200 cm−1, and extensive calculations. All of the TFE species are found to be solvated dianions, but incipient proton transfer to afford electrostatically defying anion-anion clusters is noted in two cases. In proton transfer reactions, formation of the conjugate acid as a solvated ion lowers the energy of the system and reduces the Coulomb repulsion barrier facilitating the overall process.

The equilibrium acidity of styrene was measured (ΔH°acid(PhCH CH2) = 390.6 ± 0.5 kcal mol−1) and its deprotonation site was revised from the ortho position on the aromatic ring to the α-hydrogen atom based upon deuterium-labeling studies and extensive computations. Somewhat surprisingly, the nature of the anionic base plays a critical role in properly determining the ionization site and avoiding misleading results due to extraordinary hydrogen–deuterium exchange. Bracketing the electron affinity of α-styryl radical (PhC CH2, 23.1 ± 3.4 kcal mol−1) enabled the α-C H bond dissociation energy (100.1 ± 3.4 kcal mol−1) of styrene and the effect of a phenyl substituent at an sp2-hybridized carbon to be determined. These results were compared to B3LYP, M06-2X, G3 and G4 computations.

The gas-phase acidity of ferrocene (ΔH°acid(1) = 391.5 ± 1.3 kcal mol–1) and electron affinity of the ferrocenyl radical (EA(1r) = 1.74 ± 0.08 eV) were measured in a Fourier transform mass spectrom...

A novel type of phosphoric acid catalyst with enhanced reactivity is reported. These compounds possess one or two positively charged centers which electrostatically activate them. This is illustrated in several bond-forming transformations including Friedel-Crafts and Diels-Alder reactions as well as a ring-opening polymerization. Rate accelerations corresponding to orders of magnitude are observed.

Flexible acyclic alcohols with one to five hydroxyl groups were bound to a chloride anion and these complexes were interrogated by negative ion photoelectron spectroscopy and companion density functional theory computations. The resulting vertical detachment energies are reproduced on average to 0.10 eV by M06-2X/aug-cc-pVTZ predictions and range from 4.45-5.96 eV. These values are 0.84-2.35 eV larger than the adiabatic detachment energy of Cl(-) as a result of the larger hydrogen bond networks in the bigger polyols. Adiabatic detachment energies of the alcohol-Cl(-) clusters are more difficult to determine both experimentally and computationally. This is due to the large geometry changes that occur upon photodetachment and the large bond dissociation energy of H-Cl which enables the resulting chlorine atom to abstract a hydrogen from any of the methylene (CH2) or methine (CH) positions. Both ionic and nonionic hydrogen bonds (i.e., OH···Cl(-) and OH···OH···Cl(-)) form in the larger polyols complexes and are found to be energetically comparable. Subtle structural differences, consequently can lead to the formation of different types of hydrogen bonds, and maximizing the ionic ones is not always preferred. Solution equilibrium binding constants between the alcohols and tetrabutylammonium chloride (TBACl) in acetonitrile at -24.2, +22.0, and +53.6 °C were also determined. The free energies of association are nearly identical for all of the substrates (i.e., ΔG° = -2.8 ± 0.7 kcal mol(-1)). Compensating enthalpy and entropy values reveal, contrary to expectation and the intrinsic gas-phase preferences, that the bigger systems with more hydroxyl groups are entropically favored and enthalpically disfavored relative to the smaller species. This suggests that more solvent molecules are released upon binding TBACl to alcohols with more hydroxyl groups and is consistent with the measured negative heat capacities. These quantities increase with molecular complexity of the substrate, however, contrary to common interpretation of these values.

Purpose GLUT-1 deficiency syndrome (GLUT1DS) is a neurologic disorder manifesting as epilepsy, abnormal movements, and cognitive delay. The currently accepted treatment of choice is the classic 4:1 ratio ketogenic diet. Methods A 2-page survey was distributed to all attendees of a family-centered conference for GLUT1DS in July 2015. The surveys were completed by parents, collected anonymously, and information analyzed in a database. Results Surveys were received from 92 families, of which 90 (98%) had been treated with dietary therapies. Diets used were extremely varied: 59 were treated with the classic ketogenic diet (KD), 29 with the Modified Atkins Diet (MAD), 4 with the Medium-chain Triglyceride (MCT) Diet and 2 with the low glycemic index treatment. The mean diet duration was 5.5 years (range: 1 month–20 years). Of those with seizures, 95% of the children had >50% seizure reduction and 80% had >90% seizure reduction. Children who were seizure-free were currently younger on average (8.2 vs. 11.6 years, p =0.01) and slightly younger at GLUT1DS diagnosis (3.8 vs. 5.3 years, p =0.05). There was an equal percentage of children seizure-free receiving the KD/MCT Diets compared to the MAD/Low Glycemic Index Treatment (74% vs. 63%, p =0.30). The majority (64%) were not receiving anticonvulsants. Conclusion This represents the largest series of KD experience in children with GLUT1DS. Nearly all patients surveyed were on dietary therapies for long durations with reported excellent seizure control, often without anticonvulsant drugs. Several different ketogenic diets were utilized with similar efficacy. Early diagnosis and treatment were correlated with success.

Charged thiourea derivatives containing one and two methylated or octylated pyridinium ion centers and a tetraarylborate or triflate counteranion are reported. These novel catalysts are much more active in the Friedel-Crafts reactions of trans-β-nitroalkenes with N-methylindoles than the privileged N, N'-bis(3,5-bis(trifluoromethyl)phenyl)thiourea (i.e., Schreiner's thiourea) by up to 2-3 orders of magnitude. A previously reported UV-vis spectroscopic method by Kozlowski et al. was exploited to rationalize their reactivity order along with noncharged analogues. These results offer a new design strategy for organocatalysts by introducing positively charged centers without adding additional N-H, O-H, or S-H hydrogen bond donor sites.

Measured DMSO pKa values for a series of rigid tricyclic adamantane-like triols containing 0-3 trifluoromethyl groups (i.e., 3(0)-3(3)) are reported. The three compounds with CF3 substituents are similar or more acidic than acetic acid (pKa = 13.5 (3(1)), 9.5 (3(2)), 7.3 (3(3)) vs 12.6 (HOAc)), and the resulting hydrogen bond network enables a remote γ-trifluoromethyl group to enhance the acidity as well as one located at the α-position. Catalytic abilities of 3(0)-3(3) were also examined. In a nonpolar environment a rate enhancement of up to 100-fold over flexible acyclic analogs was observed presumably due to an entropic advantage of the locked-in structure. Gas-phase acidities are found to correlate with the catalytic activity better than DMSO pKa values and appear to be a better measure of acidities in low dielectric constant media. These trends are reduced or reversed in polar solvents highlighting the importance of the reaction environment.

Hydrogen–deuterium exchange reactions of 16 small rigid anions were examined using D 2 O, CH 3 OD, CH 3 CO 2 D, and (CF 3 ) 2 C(CH 3 )OD. Bimolecular rate constants and extensive computations are reported. These deuterated reagents were used because D 2 O and CH 3 OD are weak acids that cannot react via sequential deuteron/proton transfers (i.e., the conventional H/D exchange mechanism of DePuy et al.) with the selected anions, and they provide a means to probe alternative pathways. The relative acidity of CH 3 CO 2 D and (CF 3 ) 2 C(CH 3 )OD was measured (ΔΔ H acid ° = 1.1 ± 0.8 kcal mol −1 ) and their thermodynamic similarity but structural differences (i.e., the presence of a C O in the carboxylic acid but not the alcohol) were exploited to systematically investigate flip-flop and relay mechanisms. This has led to a number of generalizations relating to the occurrence of these pathways.

The heat of hydrogenation of indenone was measured via two partially independent thermodynamic cycles by carrying out energetic measurements (i.e., electron affinities, proton affinities and ionization potentials) on both negative and positive ions (ΔH°H2 = 17.8 ± 5.5 and 17.5 ± 5.7 kcal mol−1, respectively). High level G3 computations were also carried out to provide the heats of formation of indenone (16.8 kcal mol−1) and cyclopentadienone (14.0 kcal mol−1). These 4n π electron systems are found to be nonaromatic in contrast to previous views. A recent report on cyclopropenyl anion (J. Org. Chem. 2013, 78, 7370–7372) indicates that this ion is also nonaromatic, and suggests that NMR ring currents and nucleus independent chemical shift (NICS) calculations do not correlate with the energetic criterion for antiaromatic compounds.

The title fluoroalkene has been generated by dehalogenation of dibromide and diiodide precursors and trapped in situ. retro-Diels-Alder reaction of its adduct with N-benzylpyrrole has made the alkene available in high yield and purity. In sharp contrast to its extremely labile hydrocarbon counterpart, the fluoroalkene is very stable yet highly reactive. Its characterization includes its electron affinity, photoelectron spectrum, and the previously reported structure determination by electron diffraction.

Different strategies are employed in designing strong and selective anion receptors but stereoelectronic effects have been largely ignored. In this work, the stereo configuration of a non-interacting ether is found to have a large impact of more than two orders of magnitude on the binding of a rigid diol with tetrabutylammonium chloride in acetonitrile-d3. A favorable carbon–oxygen dipole and an intramolecular C–H⋯OH hydrogen bond in an equatorially substituted ether is found to be energetically more important than a stabilizing hydrogen bond in the corresponding axially oriented alcohol. IR spectroscopy is also used to probe the structures of the bound complexes and several binding motifs are identified.

A series of neutral anion receptors with one to three thiourea arms were synthesized and their binding to tetrabutylammonium chloride, acetate, and dihydrogen phosphate salts in aqueous DMSO mixtures was examined. The three-armed thiourea host was found to strongly and selectively bind H2PO4(-) even in DMSO solutions containing up to 30% water. This enabled the dihydrogen phosphate salt to be extracted from water into chloroform in its dibasic form despite the high heat of the hydration of HPO4(2-).

Clustering an anion with one or more neutral molecules is a stabilizing process that enhances the oxidation potential of the complex relative to the free ion. Several hydrogen bond clusters (i.e., A(-) • HX, where A(-) = H2PO4(-) and CF3CO2(-) and HX = MeOH, PhOH, and Me2NOH or Et2NOH) are examined by photoelectron spectroscopy and M06-2X and CCSD(T) computations. Remarkably, these species are experimentally found to have adiabatic detachment energies that are smaller than those for the free ion and reductions of 0.47 to 1.87 eV are predicted computationally. Hydrogen atom and proton transfers upon vertical photodetachment are two limiting extremes on the neutral surface in a continuum of mechanistic pathways that account for these results, and the whole gamut of possibilities are predicted to occur.

Rigid tricyclic locked in all axial 1,3,5-cyclohexanetriol derivatives with 0-3 trifluoromethyl groups were synthesized and photoelectron spectra of their conjugate bases and chloride anion clusters are reported along with density functional computations. The resulting vertical and adiabatic detachment energies span 4.07-5.50 eV (VDE) and 3.75-5.00 (ADE) for the former ions and 5.60-6.23 eV (VDE) and 5.36-6.00 eV (ADE) for the latter species. These results provide measures of the anion stabilization due to the hydrogen bond network and inductive effects. The latter mechanism is found to be transmitted through space via hydrogen bonds, and the presence of three ring skeleton oxygen atoms and up to three trifluoromethyl groups enhance the ADEs by 1.61-2.88 eV for the conjugate bases and 1.01-1.60 eV for the chloride anion clusters. Computations indicate that the most favorable structures of the latter complexes have two hydrogen bonds to the chloride anion and one bifurcated interaction between the remote OH substituent and the two hydroxyl groups that directly bind to Cl(-).

Two new tripodal hydroxyl-based anion receptors (1 and 2) are reported and their 1:1 molecular complexes with Cl−, H2PO4−, and OAc− along with the (M − 1)− ion of 1 were characterized by negative ion photoelectron spectroscopy in the gas phase and by binding constant determinations in four solvents (i.e., CDCl3, CD2Cl2, CD3COCD3, and CD3CN). An intramolecular hydrogen bond network (HBN) in hexaol 1 was found to diminish its binding whereas the triol 2 is the strongest aliphatic hydroxyl-based receptor to date.

We report quantifying the strengths of different types of hydrogen bonds in hydrogen-bond networks (HBNs) via measurement of the adiabatic electron detachment energy of the conjugate base of a small covalent polyol model compound (i.e., (HOCH2CH2CH(OH)CH2)2CHOH) in the gas phase and the pKa of the corresponding acid in DMSO. The latter result reveals that the hydrogen bonds to the charged center and those that are one solvation shell further away (i.e., primary and secondary) provide 5.3 and 2.5 pKa units of stabilization per hydrogen bond in DMSO. Computations indicate that these energies increase to 8.4 and 3.9 pKa units in benzene and that the total stabilizations are 16 (DMSO) and 25 (benzene) pKa units. Calculations on a larger linear heptaol (i.e., (HOCH2CH2CH(OH)CH2CH(OH)CH2)2CHOH) reveal that the terminal hydroxyl groups each contribute 0.6 pKa units of stabilization in DMSO and 1.1 pKa units in benzene. All of these results taken together indicate that the presence of a charged center can provide a powerful energetic driving force for enzyme catalysis and conformational changes such as in protein folding due to multiple hydrogen bonds in a HBN.

Like-charge ion pairing is commonly observed in protein structures and plays a significant role in biochemical processes. Density functional calculations combined with the conductor-like polarizable continuum model were employed to study the formation possibilities of doubly charged noncovalently linked complexes of a series of model compounds and amino acids in the gas phase and in solution. Hydrogen bond interactions were found to offset the Coulombic repulsion such that cation-cation clusters are minima on the potential energy surfaces and neither counterions nor solvent molecules are needed to hold them together. In the gas phase the dissociation energies are exothermic, and the separation barriers span from 1.7 to 15.6 kcal mol(-1). Liquid-phase computations indicate that the separation enthalpies of the cation-cation complexes become endothermic in water and nonpolar solvents with dielectric constants of ≥7 (i.e., the value for THF). These results reveal that electrostatically defying noncovalent complexes of like-charged ions can overcome their Coulombic repulsion even in low-polarity environments.

Infrared photodissociation (IRPD) spectra are reported for a proline-chloride anion cluster along with its d2- and d7-isotopomers. The spectral data indicate that proline is in its neutral form as opposed to a zwitterion, and computations are in agreement in that some neutral conformers are energetically low-lying and reproduce the observed spectra. Zwitterionic conformers are predicted to be essentially as stable as the neutral ones and should be significantly populated; however, there is no evidence for these structures in the IRPD spectra. An exploration of the potential energy surface for the loss of chloride anion, the observed fragmentation channel, reveals that it is 8.4 kcal mol(-1) more difficult to break apart the zwitterionic cluster ion. This is a reflection of the 15.8 kcal mol(-1) estimate for the gaseous proline zwitterion-neutral energy difference. Kinetic results suggest the presence of two photolabile populations in similar amounts (i.e., 56 vs 44%). The more abundant structure is also the more labile species, and the neutral form of proline is assigned to this cluster ion. The less abundant and slower fragmenting structure consequently is zwitterionic. As originally suggested by Evans et al. in general, it appears that in this instance both spectral and kinetic data are needed to determine the structure of the proline-chloride anion cluster.

Benzene rings substituted with 1–3 thiourea containing arms (1–3) were examined by photoelectron spectroscopy and density functional theory computations. Their conjugate bases and chloride, acetate, and dihydrogen phosphate anion clusters are reported. The resulting vertical and adiabatic detachment energies span 3.93–5.82 eV (VDE) and 3.65–5.10 (ADE) for the deprotonated species and 4.88–5.97 eV (VDE) and 4.45–5.60 eV (ADE) for the anion complexes. These results reveal the stabilizing effects of multiple hydrogen bonds and anionic host–guest interactions in the gas phase. Previously measured equilibrium binding constants in aqueous dimethyl sulfoxide for all three thioureas are compared to the present results, and cooperative binding is uniformly observed in the gas phase but only for one case (i.e., 3·H2PO4–) in solution.

The α-C–H bond dissociation energy (BDE) of phenylcyclopropane (1) was experimentally determined using Hess’ law. An equilibrium acidity determination of 1 afforded ΔH°acid = 389.1 ± 0.8 kcal mol–1, and isotopic labeling established that the α-position of the three-membered ring is the favored deprotonation site. Interestingly, the structure of the base proved to be a key factor in correctly determining the proper ionization site (i.e., secondary amide ions are needed, and primary ones and OH– lead to incorrect conclusions since they scramble the deuterium label). An experimental measurement of the electron affinity of 1-phenylcyclopropyl radical (EA = 17.5 ± 2.8 kcal mol–1) was combined with the ionization energy of hydrogen (313.6 kcal mol–1) to afford BDE = 93.0 ± 2.9 kcal mol–1. This enabled the effect of the phenyl substituent to be evaluated and compared to other situations where it is attached to an sp3- or sp2-hybridized carbon center. M06-2X, CCSD(T), G4, and W1BD computations were also carried o...

A new class of readily prepared thiourea catalysts with one or more positively charged centers and no new hydrogen-bonding sites are exploited in several bond-forming reactions and are orders of magnitude more reactive than Schreiner's thiourea. These findings provide the basis for a new strategy for activating hydrogen-bond catalysts.

Enzymes and their mimics use hydrogen bonds to catalyze chemical transformations. Small-molecule transition state analogues of oxyanion holes have been characterized by computations, gas-phase IR and photoelectron spectroscopy, and determination of their binding constants in acetonitrile. A new class of hydrogen bond catalysts is proposed (donors that can contribute three hydrogen bonds to a single functional group) and demonstrated in a Friedel-Crafts reaction. The employed catalyst was observed to react 100 times faster than its rotamer that can employ only two hydrogen bonds. The former compound also binds anions more tightly and was found to have a thermodynamic advantage.

Bridgehead C-H bond dissociation enthalpies of 105.7 ± 2.0, 102.9 ± 1.7, and 102.4 ± 1.9 kcal mol(-1) for bicyclo[2.2.1]heptane, bicyclo[2.2.2]octane, and adamantane, respectively, were determined in the gas phase by making use of a thermodynamic cycle (i.e., BDE(R-H) = ΔH°(acid)(H-X) - IE(H(·)) + EA(X(·))). These results are in good accord with high-level G3 theory calculations, and the experimental values along with G3 predictions for bicyclo[1.1.1]pentane, bicyclo[2.1.1]hexane, bicyclo[3.1.1]heptane, and bicyclo[4.2.1]nonane were found to correlate with the flexibility of the ring system. Rare examples of alkyl anions in the gas phase are also provided.

Hydrogen bond interactions in small covalent model compounds (i.e., deprotonated polyhydroxy alcohols) were measured by negative ion photoelectron spectroscopy. The experimentally determined vertical and adiabatic electron detachment energies for (HOCH(2)CH(2))(2)CHO(-)(2a), (HOCH(2)CH(2))(3)CO(-) (3a), and (HOCH(2)CH(2)CH(OH)CH(2))(3)CO(-) (4a)reveal that hydrogen-bonded networks can provide enormous stabilizations and that a single charge center not only can be stabilized by up to three hydrogen bonds but also can increase the interaction energy between noncharged OH groups by 5.8 kcal mol(-1) or more per hydrogen bond. This can lead to pK(a) values that are very different from those in water and can provide some of the impetus for catalytic processes.

Deprotonation of 2-adamantanone (1) in the gas phase affords the corresponding beta-enolate anion. This ion was independently prepared by the fluoride-induced desilylation of 4-trimethylsilyl-2-adamantanone, and its reactivity and thermodynamic properties were measured (DeltaH degrees(acid) = 394.7 +/- 1.4, EA = 16.8 +/- 1.6, and BDE = 97.9 +/- 2.1 kcal mol(-1)). Density functional theory calculations with B3LYP and M06-2X, and G3 energies are also reported. The computed relative stabilities of the conjugate bases of 1 are as follows: betagammaalphadelta. An attempt to prepare the gamma-anion, however, resulted in the formation of its ring-opened isomer (i.e., deprotonated 7-methylenebicyclo[3.3.1]nonan-2-one).

Gas-phase deprotonation enthalpies were measured for chloric and perchloric acids and found to be 313.2 +/- 3.3 and 299.9 +/- 5.7 kcal mol(-1), respectively. These values were combined with the previously reported electron affinities of ClO(3) and ClO(4) to obtain BDE(H-OClO(2)) = 97.6 +/- 4.0 kcal mol(-1) and BDE(H-OClO(3)) = 107.4 +/- 6.1 kcal mol(-1). These energetic determinations represent the first measurements of these quantities or extensive revisions of the currently available values. B3LYP, M06, M06-2X, G3, and G3B3 computations also were carried out to provide acidities, electron affinities, bond dissociation energies, and heats of formation via atomization energies for ClO(x) and HClO(x), where x = 1-4. All of the methods do a reasonable job for the first three thermodynamic quantities but only M06 does a satisfactory job for the heats of formation, and its performance is similar to the highly accurate but extremely time intensive W4 method.

Hydrogen bonds are the dominant motif for organizing the three-dimensional structures of biomolecules such as carbohydrates, nucleic acids, and proteins, and serve as templates for proton transfer reactions. Computations, gas-phase acidity measurements, and pK(a) determinations in dimethyl sulfoxide on a series of polyols indicate that multiple hydrogen bonds to a single charged center lead to greatly enhanced acidities. A new class of Brønsted acids, consequently, is proposed.

The reactions of CH3 + ,C H 2Cl + and CHCl2 + with standard reference bases were examined in a dual cell Fourier transform mass spectrometer. Deprotonation of methyl cation occurs rapidly via a spin forbidden process to afford triplet methylene even when the reaction is nearly thermoneutral. Bracketing results enable us to assign PA(CHCl) = 209.7 ± 2.2 kcal mol −1 and PA(CCl2) = 205.2 ± 1.9 kcal mol −1 , the latter value of which is considerably larger than previous determinations. The resulting heats of formation, however, are in good accord with other measurements and lead to

Hydrogen-deuterium exchange experiments were carried out on the conjugate base of cysteine with four different deuterated alcohols. Three H/D exchanges are observed to take place in each case, and a relay mechanism which requires the SH and CO2H groups to have similar acidities and subsequently proceeds through a zwitterionic intermediate is proposed. Gas-phase acidity measurements also were carried out in a quadrupole ion trap using the extended kinetic method and in a Fourier transform mass spectrometer by an equilibrium determination. The results are in excellent accord with each other and high-level ab initio and density functional theory calculations and indicate that the side-chain thiol in cysteine is more acidic than the carboxyl group by 3.1 kcal mol-1. Deprotonated cysteine is thus predicted to be a thiolate ion. A zwitterionic species also was located on the potential energy surface, but it is energetically unfavorable (+10.1 kcal mol-1).

Density functional theory was used to examine the solvation number and aggregation state of several alkyllithium compounds in clusters with tetrahydrofuran molecules coordinated to each lithium atom. We then made the microsolvation approximation and approximated the bulk free energy of solvation by the free energy of clustering with solvent molecules in the gas phase. The trends in the computed results are in reasonable agreement with the available experimental data.

Acidities are commonly measured in polar solvents but catalytic reactions are typically carried out in nonpolar media. IR spectra of a series of phenols in CCl4 and 1% CD3CN/CCl4 provide relative acidities. Nonprotonated charged substituents with an appropriate counterion are found to enhance their Bronsted acidities and improve catalyst performance by orders of magnitude.

Both C-H bond dissociation energies for cyclobutene were measured in the gas phase (BDE = 91.2 +/- 2.3 (allyl) and 112.5 +/- 2.5 (vinyl) kcal mol-1) via a thermodynamic cycle by carrying out proton affinity and electron-binding energy measurements on 1- and 3-cyclobutenyl anions. The results were compared to those for an acyclic model compound, cis-2-butene, and provide the needed information to experimentally establish the heat of formation of cyclobutadiene. Chemically accurate G3 and W1 calculations also were carried out on cycloalkanes, cycloalkenes, and selected reference compounds. It appears that commonly cited bond energies for cyclopropane, cyclobutane, and cyclohexane are 3 to 4 kcal mol-1 too small and their pi bond strengths, as given by BDE1 - BDE2, are in error by up to 8 kcal mol-1.

Natural and synthetic anion receptors are extensively employed, but the structures of their bound complexes are difficult to determine in the liquid phase. Infrared spectroscopy is used in this work to characterize the solution structures of bound anion receptors for the first time, and surprisingly only two of three hydroxyl groups of the neutral aliphatic triols are found to directly interact with Cl(–). The binding constants of these triols with zero to three CF3 groups were measured in a polar environment, and KCD3CN(Cl(–)) = 1.1 × 10(6) M(–1) for the tris(trifluoromethyl) derivative. This is a remarkably large value, and high selectivity with respect to interfering anions such as, Br(–), NO3(–) and NCS(–) is also displayed. The effects of the third “noninteracting” hydroxyl groups on the structures and binding constants were also explored, and surprisingly they are as large or larger than the OH substituents that hydrogen bond to Cl(–). That is, a remote hydroxyl group can play a larger role in binding than two OH substituents that directly interact with an anionic center.

The heat of hydrogenation of phenylcyclobutadiene (DeltaH degrees (hyd) = 57.4 +/- 4.9 kcal mol(-1)) was determined via a thermodynamic cycle by carrying out gas-phase measurements on 1-phenylcyclobuten-3-yl cation. This leads to an antiaromatic destabilization energy of 27 +/- 5 kcal mol(-1), a difference of 9.6 +/- 4.9 kcal mol(-1) for the first and second C-H bond dissociation energies of 1-phenylcyclobutene, and an estimate of 96 +/- 5 kcal mol(-1) for the heat of formation of cyclobutadiene. These results are compared to G3, G3(MP2), and B3LYP computations and represent the first experimental measurements of the energy of a monocyclic cyclobutadiene.

Organolithium compounds RLi (R = CH(3), CH(3)CH(2), CH(2)=CH, and HC(triple bond)C) and their corresponding hydrocarbons were fully optimized at the MP2/6-311+G(2df,2pd) level. Single-point energy calculations also were carried out at the CCSD(T) and B3LYP levels with the same triple split-valence basis set. Acidities, electron affinities, and bond dissociation energies are reported, and the following general results were found: (1) Alpha-lithio anions are ground-state triplet molecules. (2) Lithium is an acid-enhancing substituent. (3) Conjugate bases of organolithiums are stable with respect to electron loss and therefore are attractive targets for mass spectrometry investigations. (4) Lithium weakens alpha- and beta-C-H bonds, the latter by approximately 25 kcal mol(-1). Consequently, radical chemistry of lithiated compounds at remote sites is a promising area for exploration.

The gas-phase acidity of 3,3-dimethylcyclopropene (1) has been measured by bracketing and equilibrium techniques. Consistent with simple hybridization arguments, our value (deltaH degrees (acid) = 382.7 +/- 1.3 kcal mol(-)(1)) is indistinguishable from that for methylacetylene (i.e., deltadeltaH degrees (acid)(1 - CH(3)Ctbd1;CH) = 1.6 +/- 2.5 kcal mol(-)(1)). The electron affinity of 3,3-dimethylcyclopropenyl radical (1r) was also determined (EA = 37.6 +/- 3.5 kcal mol(-)(1)), and these quantities were combined in a thermodynamic cycle to afford the homolytic C-H bond dissociation energy. To our surprise, the latter quantity (107 +/- 4 kcal mol(-)(1)) is the same as that for methane, which cannot be explained in terms of the s-character in the C-H bonds. An orbital explanation (delocalization) is proposed to account for the extra stability of 1r. All of the results are supplemented with G3 and B3LYP computations, and both approaches are in good accord with the experimental values. We also note that for simple hydrocarbons which give localized carbanions upon deprotonation there is an apparent linear correlation between any two of the following three quantities: deltaH degrees (acid), BDE, and EA. This observation could be of considerable value in many diverse areas of chemistry.

Negative ion photoelectron spectra resulting from the decarboxylation of nine zwitterionic pyridinium dicarboxylates (D(x,y)) are reported. Structural assignments are made on the basis of analogy to the spectra of related species, labeling experiments with (13)C- or (2)H-containing substrates, independent syntheses, and comparison to density functional theory and ab initio (B3LYP and CCSD(T), respectively) results. In some cases, an acid-catalyzed isomerization of the D(x,y)-CO(2) ions was found to take place. Adiabatic detachment energies of the resulting zwitterionic ions were measured and are well reproduced by theory. The relative stabilities of the D(x,y)-CO(2) decarboxylation products are largely determined by their intramolecular electrostatic interactions, which are directly probed by the photoelectron spectra and were analyzed in terms of the resulting Coulombic forces. Expulsion of carbon dioxide from the D(x,y) ions was also used as an electrostatic model to probe the mechanism of the enzyme-catalyzed conversion of orotidine 5'-monophosphate (OMP) to uridine 5'-monophosphate (UMP). It was found that the loss of CO(2) from these zwitterions and from oxygen-protonated OMP is retarded by the presence of an additional anionic group. This suggests that the formation of a zwitterion intermediate in the enzyme-catalyzed transformation of OMP to UMP may have less of an energetic impact than commonly thought and could be a "red herring". If so, the electrostatic stress mechanism proposed by Larsen et al. and Pai, Guo, and co-workers maybe followed.

We have regiospecifically generated the α,2-, α,3-, and α,4-dehydrophenoxide anions by collisional activation of o-, m-, and p-nitrobenzoate. The α,2 and α,4 isomers also were synthesized by reacting o-benzyne radical anion with carbon dioxide and electron ionization of p-diazophenol. All three dehydrophenol radical anions were differentiated from each other and identified by probing their chemical reactivity with several reagents. Each isomer was converted to phenoxide and its corresponding quinone as well. Thermochemical measurements were carried out on all three radical anions and their hydrogen-atom affinities, proton affinities, and electron binding energies are reported. These measured quantities are combined in thermodynamic cycles to derive the heats of formation of each of the radical anions and their corresponding carbenes (i.e., α,2-, α,3-, and α,4-dehydrophenol). These results are compared to MCQDPT2, G3, G2+(MP2), and B3LYP calculations and experimental data for appropriate reference compounds.