Structures of lithiated lysine and structural analogues in the gas phase: effects of water and proton affinity on zwitterionic stability

The structures of lithiated lysine, ornithine, and related molecules, both with and without a water molecule, are investigated using both density functional theory and blackbody infrared radiative dissociation experiments. The lowest-energy structure of lithiated lysine without a water molecule is nonzwitterionic; the metal ion interacts with both nitrogen atoms and the carbonyl oxygen. Structures in which lysine is zwitterionic are higher in energy by more than 29 kJ/mol. In contrast, the singly hydrated clusters with the zwitterionic and nonzwitterionic forms of lysine are more similar in energy, with the nonzwitterionic form more stable by only approximately 7 kJ/mol. Thus, a single water molecule can substantially stabilize the zwitterionic form of an amino acid. Analogous molecules that have methyl groups attached to either the N-terminus (NMeLys) or the side-chain amine (Lys(Me)) have proton affinities greater than that of lysine. In the lithiated clusters with a water molecule attached, the zwitterionic forms of NMeLys and Lys(Me) are calculated to be approximately 4 and approximately 11 kJ/mol more stable than the nonzwitterionic forms, respectively. Calculations of the potential-energy pathway for interconversion between the different forms of lysine in the lithiated complex indicate multiple stable intermediates with an overall barrier height of approximately 83 kJ/mol between the lowest-energy nonzwitterionic form and the most accessible zwitterionic form. Experimentally determined binding energies of water are similar for all these complexes and range from 57 to 64 kJ/mol. These results suggest that loss of a water molecule from the lysine complexes is both energetically and entropically favored compared to interconversion between the nonzwitterionic and zwitterionic structures. Comparisons to calculated binding energies of water to the various structures show that the experimental results are most consistent with the nonzwitterionic forms.     

Binding energies of water to doubly hydrated cationized glutamine and structural analogues in the gas phase

The modes of metal-ion and water binding in doubly hydrated complexes of lithiated and sodiated glutamine (Gln) are probed using blackbody infrared radiative dissociation experiments and density functional theory calculations. Threshold dissociation energies, E0, for loss of a water molecule from these complexes are obtained from master-equation modeling of these data. The values of E0 are 36 +/- 1 and 38 +/- 2 kJ/mol for the lithiated and sodiated glutamine complexes, respectively, and are consistent with calculated water binding energies for the nonzwitterionic form of these complexes. Calculated water binding energies for the zwitterionic forms of these complexes are significantly higher. In contrast, calculations indicate that the zwitterionic form of Gln in these complexes is more stable than the nonzwitterionic form by 8 and 15 kJ/mol when lithiated and sodiated, respectively. Doubly hydrated lithiated and sodiated complexes of asparagine methyl ester (AsnOMe), asparagine ethyl ester (AsnOEt), and glutamine methyl ester (GlnOMe) were also studied for comparison to Gln. Although these clusters lack the acidic group of Gln and therefore have different water coordination behavior, these results further support the conclusion that Gln is nonzwitterionic in these clusters. Surprisingly, the complexes containing sodium are more stable than those containing lithium, a result that is attributed to subtle differences in how these two metal ions bind to the amino acid esters in these complexes.     

Binding energies of protonated betaine complexes: a probe of zwitterion structure in the gas phase

The dissociation kinetics of proton-bound dimers of betaine with molecules of comparable gas-phase basicity were investigated using blackbody infrared radiative dissociation (BIRD). Threshold dissociation energies were obtained from these data using master equation modeling. For bases that have comparable or higher gas-phase basicity, the binding energy of the protonated base.betaine complex is ~1.4 eV. For molecules that are ~2 kcal/mol or more less basic, the dissociation energy of the complexes is ~1.2 eV. The higher binding energy of the former is attributed to an ion-zwitterion structure which has a much larger ion-dipole interaction. The lower binding energy for molecules that are ~2 kcal/mol or more less basic indicates that an ion-molecule structure is more favored. Semiempirical calculations at both the AM1 and PM3 levels indicate the most stable ion-molecule structure is one in which the base interacts with the charged quaternary ammonium end of betaine. These results indicate that the measurement of binding energies of neutral molecules to biological ions could provide a useful probe for the presence of zwitterions and salt bridges in the gas phase. From the BIRD data, the gas-phase basicity of betaine obtained from the kinetic method is found to be 239.2 +/- 1.0 kcal/mol. This value is in excellent agreement with the value of 239.3 kcal/mol (298 K) from ab initio calculations at the MP2/6-31+g** level. The measured value is slightly higher than those reported previously. This difference is attributed to entropy effects. The lower ion internal energy and longer time frame of BIRD experiments should provide values closer to those at standard temperature.     

Infrared spectroscopy of cationized lysine and epsilon-N-methyllysine in the gas phase: effects of alkali-metal ion size and proton affinity on zwitterion stability

The gas-phase structures of protonated and alkali-metal-cationized lysine (Lys) and epsilon-N-methyllysine (Lys(Me)) are investigated using infrared multiple photon dissociation (IRMPD) spectroscopy utilizing light generated by a free electron laser, in conjunction with ab initio calculations. IRMPD spectra of Lys.Li(+) and Lys.Na(+) are similar, but the spectrum for Lys.K(+) is different, indicating that the structure of lysine in these complexes depends on the metal ion size. The carbonyl stretch of a carboxylic acid group is clearly observed in each of these spectra, indicating that lysine is nonzwitterionic in these complexes. A detailed comparison of these spectra to those calculated for candidate low-energy structures indicates that the bonding motif for the metal ion changes from tricoordinated for Li and Na to dicoordinated for K, clearly revealing the increased importance of hydrogen-bonding relative to metal ion solvation with increasing metal ion size. Spectra for Lys(Me).M(+) show that Lys(Me), an analogue of lysine whose side chain contains a secondary amine, is nonzwitterionic with Li and zwitterionic with K and both forms are present for Na. The proton affinity of Lys(Me) is 16 kJ/mol higher than that of Lys; the higher proton affinity of a secondary amine can result in its preferential protonation and stabilization of the zwitterionic form.     

Binding energies of water to lithiated valine: Formation of solution-phase structure in vacuo

Dissociation kinetics for loss of a water molecule from hydrated ions of lithiated valine, alanine ethyl ester and betaine are determined using blackbody infrared radiative dissociation at temperatures between -60 and 110 degrees C. From master equation modeling of these data, values of the threshold dissociation energy are obtained for clusters containing one through three water molecules. By comparing the values for valine with its two isomers, one a model for the nonzwitterion structure, the other a model for the zwitterion structure, information about the structure of valine in these hydrated clusters is inferred. Structures, relative energies, and water binding energies for these ions are also calculated at the B3LYP/6-31++G** level of theory. With one water molecule, both experiment and theory indicate that valine is not a zwitterion and that the lithium ion coordinates with the amino nitrogen and the carbonyl oxygen (NO coordinated) and the water molecule interacts directly with the lithium ion. With two water molecules, the zwitterion and nonzwitterion structures are nearly isoenergetic, but the experiment clearly indicates a NO-coordinated nonzwitterion structure. With three water molecules, both the experimental data and theory indicate that the lithium ion binds to the carboxylate group of valine, i.e., valine is zwitterionic with three water molecules. The agreement between the experimentally determined and calculated binding energies is good for all the clusters, with deviations of <== 0.12 eV.     

Vibrational signature of charge solvation vs salt bridge isomers of sodiated amino acids in the gas phase

The vibrational spectra of the gaseous sodium complexes of glycine (Gly-Na(+)) and proline (Pro-Na(+)) have been recorded in the spectral range 1150-2000 cm(-1). The complexes were formed by matrix-assisted laser desorption-ionization, introduced in the cell of a Fourier transform ion cyclotron resonance mass spectrometer, and their infrared spectra were recorded using photons of variable energy emitted by a free electron laser. Photon absorption was probed by the diminished intensity of the parent ion, due to its infrared-induced dissociation into bare sodium cation and the free amino acid and the appearance of Na(+). The observed absorption bands are assigned using ab initio computations of the IR spectra of the lowest energy isomers in each case. They provide the first experimental evidence that the salt bridge isomer is formed in the case of Pro-Na(+). In contrast, charge solvation by chelation of Na(+) between nitrogen and the carbonyl oxygen seems to be most favorable for Gly-Na(+), but a mixture of isomers cannot be ruled out in this case.     

Slow proton exchange in water in the gas phase

To study proton exchange in water the technique of quantitative measurements of water content at very low concentrations of water in solutions or at low vapor pressure in the gas phase (for water content of 1–10 μg/ml) has been developed. Under these conditions the rate of proton exchange slows down significantly. In particular, in mixtures of H₂O and D₂O vapors under the pressure of a 10–17 mm Hg proton life-time during the exchange process reaches the values of 10–30 min. The lifetime was measured using the gradual slow growth of the signal intensity of the mixed isotopomer HDO.     

Niobium oxochlorides in the gas phase: Quantum chemical calculations of the structure and relative stability of isomers

The gas-phase niobium oxochloride anions that result by the interaction between the finely dispersed stereoselective acetylene cyclotrimerization catalyst NbCl₂(C _n H _n ) (n = 10–12) and atmospheric oxygen and moisture have been characterized by matrix-assisted laser desorption/ionization (MALDI) time-of-flight mass spectrometry. From the relative intensities of mass spectrometric lines, it has been deduced that, among the various niobium oxochloride species passing into the gas phase under the action of laser radiation, the most abundant monomer ion is NbO₂Cl ₂ ^? , the most abundant dimers are Nb₂O₄Cl ₃ ^? and Nb₂O₃Cl ₅ ^? , the most abundant trimer is Nb₃O₆Cl ₅ ^? , and the most abundant tetramer is Nb₄O₈Cl ₅ ^? . The gas phase also contains low concentrations of fragments corresponding to the pentanuclear anion Nb₃O₁₁Cl ₄ ^? and the hexanuclear anion Nb₆O₁₅Cl ₂ ^? . The geometric parameters and total energy of the stable isomers of the dinuclear and polynuclear niobium oxochloride anions existing in the gas phase has been calculated by quantum chemical methods, and their relative thermodynamic stabilities have been determined for different metal core configurations and different arrangements of oxygen and chlorine ions. The stereochemistry of the niobium oxochlorides is discussed.     

Acidity and proton affinity of hypoxanthine in the gas phase versus in solution: intrinsic reactivity and biological implications

Hypoxanthine is a mutagenic purine base that most commonly arises from the oxidative deamination of adenine. Damaged bases such as hypoxanthine are associated with carcinogenesis and cell death. This inevitable damage is counteracted by glycosylase enzymes, which cleave damaged bases from DNA. Alkyladenine DNA glycosylase (AAG) is the enzyme responsible for excising hypoxanthine from DNA in humans. In an effort to understand the intrinsic properties of hypoxanthine, we examined the gas-phase acidity and proton affinity using quantum mechanical calculations and gas-phase mass spectrometric experimental methods. In this work, we establish that the most acidic site of hypoxanthine has a gas-phase acidity of 332 +/- 2 kcal mol-1, which is more acidic than hydrochloric acid. We also bracket a less acidic site of hypoxanthine at 368 +/- 3 kcal mol-1. We measure the proton affinity of the most basic site of hypoxanthine to be 222 +/- 3 kcal mol-1. DFT calculations of these values are consistent with the experimental data. We also use calculations to compare the acidic and basic properties of hypoxanthine with those of the normal bases adenine and guanine. We find that the N9-H of hypoxanthine is more acidic than that of adenine and guanine, pointing to a way that AAG could discriminate damaged bases from normal bases. We hypothesize that AAG may cleave certain damaged nucleobases as anions and that the active site may take advantage of a nonpolar environment to favor deprotonated hypoxanthine as a leaving group versus deprotonated adenine or guanine. We also show that an alternate mechanism involving preprotonation of hypoxanthine is energetically less attractive, because the proton affinity of hypoxanthine is less than that of adenine and guanine. Last, we compare the acidity in the gas phase versus that in solution and find that a nonpolar environment enhances the differences in acidity among hypoxanthine, adenine, and guanine.     

Fragmentation and deformation mechanism of glycine isomers in gas phase: Investigations of charge effect

The structural parameters, relative stability, proton transfer energy barriers of four typical and life related isomers and conformers of different charged (n=0,+/-1,+/-2) glycine species have been investigated using B3LYP, BHLYP, and CCSD(T) methods. Results indicate that those neutral and (+/-1)-charged species are stable. For the (+2)-charged cases, all four triplet-state glycine species and only the singlet-state zwitterionic one are stable. On the other hand, only the singlet-state zwtterionic glycine ((1)GlyZW(-2)) and the corresponding neutral form counterpart ((1)Gly(-2)) are stable for the (-2)-charged cases. Either of the two stable structures holds a proton lying in the position (2-3 A) of being separated from its corresponding parental species. Those unstable divalent glycine species are dissociated into different smaller species spontaneously according to the characters of their different structures and electron spins. The presented fragmentation and deformation mechanisms can effectively predict and satisfactorily explain some experimental phenomena, which had been puzzling the mass spectrometry chemists. Also, the mechanisms should be suitable for any other similar molecule systems. Comparisons of the relative energies of the four (+1)-charged glycine species show that doublet-state glycine III ((2)GlyIII1) is more stable in energy by 12.1 kcal/mol than the (+1)-charged glycine Gly ((2)Gly1). This is consistent with the energy ordering of their corresponding mono-valence metal ion-bound derivatives. In addition, calculations show that an intramolecular proton transfer of (2)Gly(-1) to become its zwitterionic counterpart is preferred due to its least activation energy barrier (5.8 kcal/mol) among four discussed processes.     

Dissociative electron attachment to gas phase valine: a combined experimental and theoretical study

Using a crossed electron/molecule beam technique the dissociative electron attachment (DEA) to gas phase L-valine, (CH(3))(2)CHCH(NH(2))COOH, is studied by means of mass spectrometric detection of the product anions. Additionally, ab initio calculations of the structures and energies of the anions and neutral fragments have been carried out at G2MP2 and B3LYP levels. Valine and the previously studied aliphatic amino acids glycine and alanine exhibit several common features due to the fact that at low electron energies the formation of the precursor ion can be characterized by occupation of the pi* orbital of the carboxyl group. The dominant negative ion (M-H)(-) (m/Z=116) is observed at electron energies of 1.12 eV. This ion is the dominant reaction product at electron energies below 5 eV. Additional fragment ions with m/Z=100, 72, 56, 45, 26, and 17 are observed both through the low lying pi* and through higher lying resonances at about 5.5 and 8.0-9.0 eV, which are characterized as core excited resonances. According to the threshold energies calculated here, rearrangements play a significant role in the formation of DEA fragments observed from valine at subexcitation energies.     

Alkali metal ion binding to amino acids versus their methyl esters: affinity trends and structural changes in the gas phase

The relative alkali metal ion (M(+)) affinities (binding energies) between seventeen different amino acids (AA) and the corresponding methyl esters (AAOMe) were determined in the gas phase by the kinetic method based on the dissociation of AA-M(+)-AAOMe heterodimers (M=Li, Na, K, Cs). With the exception of proline, the Li(+), Na(+), and K(+) affinities of the other aliphatic amino acids increase in the order AAAAOMe is already observed for K(+). Proline binds more strongly than its methyl ester to all M(+) except Li(+). Ab initio calculations on the M(+) complexes of alanine, beta-aminoisobutyric acid, proline, glycine methyl ester, alanine methyl ester, and proline methyl ester show that their energetically most favorable complexes result from charge solvation, except for proline which forms salt bridges. The most stable mode of charge solvation depends on the ligand (AA or AAOMe) and, for AA, it gradually changes with metal ion size. Esters chelate all M(+) ions through the amine and carbonyl groups. Amino acids coordinate Li(+) and Na(+) ions through the amine and carbonyl groups as well, but K(+) and Cs(+) ions are coordinated by the O atoms of the carboxyl group. Upon consideration of these differences in favored binding geometries, the theoretically derived relative M(+) affinities between aliphatic AA and AAOMe are in good overall agreement with the above given experimental trends. The majority of side chain functionalized amino acids studied show experimentally the affinity order AAAAOMe. The latter ranking is attributed to salt bridge formation.     

Infrared spectroscopy of hydrated amino acids in the gas phase: protonated and lithiated valine

We report here infrared spectra of protonated and lithiated valine with varying degrees of hydration in the gas phase and interpret them with the help of DFT calculations at the B3LYP/6-31++G** level. In both the protonated and lithiated species our results clearly indicate that the solvation process is driven first by solvation of the charge site and subsequently by formation of a second solvation shell. The infrared spectra of Val x Li+ (H2O)4 and Val x H+ (H2O)4 are strikingly similar in the region of the spectrum corresponding to hydrogen-bonded stretches of donor water molecules, suggesting that in both cases similar extended water structures are formed once the charge site is solvated. In the case of the lithiated species, our spectra are consistent with a conformation change of the amino acid backbone from syn to anti accompanied by a change in the lithium binding from a NO coordination to OO coordination configuration upon addition of the third water molecule. This change in the mode of metal ion binding was also observed previously by Williams and Lemoff [J. Am. Soc. Mass Spectrom. 2004, 15, 1014-1024] using blackbody infrared radiative dissociation (BIRD). In contrast to the zwitterion formation inferred from results of the BIRD experiments upon addition of a third water molecule, our spectra, which are a more direct probe of structure, show no evidence for zwitterion formation with the addition of up to four water molecules.     

Theoretical prediction of proton and electron affinities,gas phase basicities,and ionization energies of sulfinamides

Structural Chemistry - Sulfinamides, as an asymmetric synthesizer, especially in drug synthesis, play critical roles in organic chemistry. In this study, the gas phase ion energetics data including...     

Excited state proton transfer in guanine in the gas phase and in water solution: a theoretical study

Theoretical investigations were performed to study the phenomena of ground and electronic excited state proton transfer in the isolated and monohydrated forms of guanine. Ground and transition state geometries were optimized at both the B3LYP/6-311++G(d,p) and HF/6-311G(d,p) levels. The geometries of tautomers including those of transition states corresponding to the proton transfer from the keto to the enol form of guanine were also optimized in the lowest singlet pipi* excited state using the configuration interaction singles (CIS) method and the 6-311G(d,p) basis set. The time-dependent density function theory method augmented with the B3LYP functional (TD-B3LYP) and the 6-311++G(d,p) basis set was used to compute vertical transition energies using the B3LYP/6-311++G(d,p) geometries. The TD-B3LYP/6-311++G(d,p) calculations were also performed using the CIS/6-311G(d,p) geometries to predict the adiabatic transition energies of different tautomers and the excited state proton transfer barrier heights of guanine tautomerization. The effect of the bulk aqueous environment was considered using the polarizable continuum model (PCM). The harmonic vibrational frequency calculations were performed to ascertain the nature of potential energy surfaces. The excited state geometries including that of transition states were found to be largely nonplanar. The nonplanar fragment was mostly localized in the six-membered ring. Geometries of the hydrated transition states in the ground and lowest singlet pipi* excited states were found to be zwitterionic in which the water molecule is in the form of hydronium cation (H3O(+)) and guanine is in the anionic form, except for the N9H form in the excited state where water molecule is in the hydroxyl anionic form (OH(-)) and the guanine is in the cationic form. It was found that proton transfer is characterized by a high barrier height both in the gas phase and in the bulk water solution. The explicit inclusion of a water molecule in the proton transfer reaction path reduces the barrier height drastically. The excited state barrier height was generally found to be increased as compared to that in the ground state. On the basis of the current theoretical calculation it appears that the singlet electronic excitation of guanine may not facilitate the excited state proton transfer corresponding to the tautomerization of the keto to the enol form.     

Thermochemical aspects of proton transfer in the gas phase

The beginning of the twentieth century saw the development of new theories of acidity and basicity, which are currently well accepted. The thermochemistry of proton transfer in the absence of solvent attracted much interest during this period, because of the fundamental importance of the process. Nevertheless, before the 1950s, few data were available, either from lattice energy evaluations or from calculations using the emerging molecular orbital theory. Advances in mass spectrometry during the last 40 years allowed studies of numerous systems with better accuracy. Thousands of accurate gas-phase acidities or basicities are now available, for simple atomic and molecular systems and for large biomolecules. The intrinsic effect of structure on the Br?nsted basic or acidic properties of molecules and the influence of solvents have been unravelled. In this tutorial, the basics of the thermodynamic principles involved are given, and the mass spectrometric techniques are briefly reviewed. Advances in the design and measurements of gas-phase superacids and superbases are described. Recent studies concerning biomolecules are also evoked.     

Isolation of isomers based on hydrogen/deuterium exchange in the gas phase

A method to isolate isomers in a Fourier transform ion cyclotron resonance mass spectrometer on the basis of their different hydrogen/deuterium exchange rates has been developed and applied to the protonated serine octamer cluster. Isolation allows interrogation of each isomer by infrared multi-photon dissociation to determine any differences in the building blocks that form these clusters. The experimental results strongly support previous assignments of an all-zwitterion structure to the slower-exchanging isomer and an all-neutral structure to its faster- exchanging counterpart.     

Reactivity of gaseous sodiated ions derived from benzene dicarboxylate salts toward residual water in the collision gas

The sodium adduct of disodium salts of benzene dicarboxylic acids (m/z 233), when subjected to collision‐induced dissociation (CID), undergoes a facile loss of CO₂ to produce an ion of m/z 189, which retains all the three sodium atoms of the precursor. The CID spectrum of this unusual m/z 189 ion shows significant peaks at m/z 167, 63 and 85. The enigmatic m/z 167 ion, which appeared to represent a loss of a 22‐Da neutral fragment from the precursor ion is in fact a fragment produced by the interaction of the m/z 189 ion with traces of water present in the collision gas. The change of the m/z 167 peak to 168, when D₂O vapor was introduced to the collision gas of a Q‐ToF instrument, proved that such an intervention of water could occur even in collision cells of tandem‐in‐space mass spectrometers. The m/z 189 ion has such high affinity for water; it forms an ion/molecule complex even during the brief residence time of ions in collision cells of triple quadrupole instruments. The complex formed in this way then eliminates elements of NaOH to produce the ion observed at m/z 167. In an ion trap, the relative intensity of the m/z 167 peak increases with longer activation time even at the lowest possible collision energy setting. Similarly, the m/z 145 ion (which represents the sodium adduct of phenelenedisodium, formed by two consecutive losses of CO₂ from the m/z 233 ion of meta‐ and para‐isomers) interacts with water to produce a fragment ion at m/z 123 for the sodium adduct of phenylsodium. Other uncommon ions that originate also from water/ion interactions are observed at m/z 85 and 63 for [Na₃O]⁺ and [Na₂OH]⁺, respectively. Tandem mass spectrometric experiments conducted with appropriately deuterium‐labeled compounds confirmed that the proton required for the formation of the [Na₂OH]⁺ ion originates from traces of water present in the collision gas and not from the ring protons of the aromatic moiety. Copyright © 2010 John Wiley & Sons, Ltd.     

Structure of cationized glycine, gly.m (m = be, mg, ca, sr, ba), in the gas phase: intrinsic effect of cation size on zwitterion stability

Interactions between divalent metal ions and biomolecules are common both in solution and in the gas phase. Here, the intrinsic effect of divalent alkaline earth metal ions (Be, Mg, Ca, Sr, Ba) on the structure of glycine in the absence of solvent is examined. Results from both density functional and Moller-Plesset theories indicate that for all metal ions except beryllium, the salt-bridge form of the ion, in which glycine is a zwitterion, is between 5 and 12 kcal/mol more stable than the charge-solvated structure in which glycine is in its neutral form. For beryllium, the charge-solvated structure is 5-8 kcal/mol more stable than the salt-bridge structure. Thus, there is a dramatic change in the structure of glycine with increased metal cation size. Using a Hartree-Fock-based partitioning method, the interaction between the metal ion and glycine is separated into electrostatic, charge transfer and deformation components. The charge transfer interactions are more important for stabilizing the charge-solvated structure of glycine with beryllium relative to magnesium. In contrast, the difference in stability between the charge-solvated and salt-bridge structure for magnesium is mostly due to electrostatic interactions that favor formation of the salt-bridge structure. These results indicate that divalent metal ions dramatically influence the structure of this simplest amino acid in the gas phase.     

The gas phase structures of the isomers of benzene: IV. Hexafluoro-dewar-benzene

Gas phase electron diffraction data for HFDB were analyzed, following conventional procedures, and a structure was deduced for the perfluoro-bicyclo-[2.2.0]hexa-2,5-diene consistent with its C_2v symmetry. A least squares analysis of the molecular scattering function gave the following r_g values: [-C-C-] = 1.597 ± 0.006 Å, [C-C-] = 1.503 ± 0.002 Å, [-C-C-] = 1.356 ± 0.007 Å, [-C-F](bridge) = 1.331 ± 0.008 Å, [-C-F] (terminal) = 1.323 ± 0.004 Å. The flap angle between the rings is 115.3( ± .7)°. The terminal fluorines are in the planes of the corresponding rings.The most notable feature of the structure is the long C-C bridge bond, which was also observed in hexamethyl-Dewar-benzene. The geometrical features of HFDB are compared with corresponding ones in HMDB, and with perfluoro- cyclobutene as well as with theoretical estimates.