Conformational studies by dynamic NMR. 99. Experimental and computed determination of rotation barriers in the crystalline state: the case of naphthylphenylsulfoxide

The (13)C NMR CP-MAS spectrum of 2-naphthylphenylsulfoxide in the solid state displays line broadening effects due to the restricted rotation about the Ph-S bond. Line shape simulation of the temperature-dependent traces allowed the corresponding barrier to be determined in the solids (14.7 kcal mol(-1)). By making use of the information obtained from single-crystal X-ray diffraction, this barrier could be satisfactorily reproduced by theoretical calculations (14.5 kcal mol(-1)) that take into account the correlated phenyl motion involving a large set of molecules in the crystalline state     

Theoretical study of 1,6-anhydrosugar formation from phenyl D-glucosides under basic condition: reasons for higher reactivity of β-anomer

Degradation of anomeric phenyl d-glucosides to levoglucosan under basic condition is theoretically studied. MP4(SDQ)//DFT(B3LYP)-computational results indicate that the degradation of phenyl α-glucoside (R(α)) occurs via the S(N)icB mechanism. In this mechanism, the oxyanion at the C6, which is formed through deprotonation of the OH group, directly attacks the anomeric carbon. On the other hand, the degradation of phenyl β-glucoside (R(β)) occurs via the S(N)icB(2) mechanism. In this mechanism, the oxyanion at the C2 attacks the anomeric carbon in a nucleophilic manner to afford 1,2-anhydride intermediate and then the oxyanion at the C6 attacks the anomeric carbon to afford levoglucosan. The activation barrier is much lower in the reaction of R(β) (ΔG(0++) = 25.6 kcal/mol and E(a) = 26.5 kcal/mol) than in the reaction of R(α) (ΔG(0++) = 38.1 kcal/mol and E(a) = 37.2 kcal/mol), which is consistent with the experimental observation that β-glucoside is generally much more reactive than the corresponding α-glucoside. The lower activation barrier of the reaction of R(β) arises from the stereoelectronic effect, which is induced by the charge transfer from the ring oxygen to the anomeric carbon, and the staggered conformation around the C1-C2 bond. When the stereoelectronic effect is absent, the degradation needs larger activation energy; for instance, the degradation of phenyl 5a-carba-β-d-glucoside (R(Cβ)) occurs with large ΔG(0++) and E(a) values like those of α-glucosides, because the methylene group of R(Cβ) does not contribute to the stereoelectronic effect. Also, the conformation around the C1-C2 bond is staggered in the transition state of the R(β) reaction but eclipsed in that of the R(α) reaction, which also leads to the larger reactivity of R(β).     

Conformational studies by dynamic NMR. 74.(1) stereomutations of the conformational enantiomers in peri-substituted 1-acylnaphthalenes

Naphthalenes bearing an acyl and a phenyl group in a peri relationship give rise to a pair of enantiomers in the temperature range where the rotations of the acyl group are slow. Such enantiomers were observed by means of low temperature NMR spectra in chiral environments. The barrier to rotation for the acyl substituents, that causes the interconversion of the enantiomers, was demonstrated to be lower than that for the phenyl group. In an appropriately synthesized derivative it was possible to measure the two barriers that were found equal to 10.4 and 15.9 kcal mol(-)(1), respectively. The barriers for the acyl group rotation increase regularly (from 9.5 to 13.2 kcal mol(-)(1)) with the increasing dimension of the RCO groups (R = Me, Et, Pr(i), Bu(t)). When a bromine atom replaces the phenyl group, the enantiomerization barrier for the corresponding acyl derivatives increases significantly.     

Chemo- and periselectivity in the addition of [OsO2(CH2)2] to ethylene: a theoretical study

Quantum chemical calculations by using density functional theory at the B3LYP level have been carried out to elucidate the reaction course for the addition of ethylene to [OsO2(CH2)2] (1). The calculations predict that the kinetically most favorable reaction proceeds with an activation barrier of 8.1 kcal mol(-1) via [3+2] addition across the O=Os=CH2 moiety. This reaction is -42.4 kcal mol(-1) exothermic. Alternatively, the [3+2] addition to the H2C=Os=CH2 fragment of 1 leads to the most stable addition product 4 (-72.7 kcal mol(-1)), yet this process has a higher activation barrier (13.0 kcal mol(-1)). The [3+2] addition to the O=Os=O fragment yielding 2 is kinetically (27.5 kcal mol(-1)) and thermodynamically (-7.0 kcal mol(-1)) the least favorable [3+2] reaction. The formal [2+2] addition to the Os=O and Os=CH2 double bonds proceeds by initial rearrangement of 1 to the metallaoxirane 1 a. The rearrangement 1-->1 a and the following [2+2] additions have significantly higher activation barriers (>30 kcal mol(-1)) than the [3+2] reactions. Another isomer of 1 is the dioxoosmacyclopropane 1 b, which is 56.2 kcal mol(-1) lower in energy than 1. The activation barrier for the 1-->1 b isomerization is 15.7 kcal mol(-1). The calculations predict that there are no energetically favorable addition reactions of ethylene with 1 b. The isomeric form 1 c containing a peroxo group is too high in energy to be relevant for the reaction course. The accuracy of the B3LYP results is corroborated by high level post-HF CCSD(T) calculations for a subset of species.     

Facile η5-η3 hapticity interconversion in pentamethylcyclopentadienyl ruthenium(II) complexes containing a phenylmethallyl ("open indenyl") ligand

The indenyl effect has been introduced to pentadienyl ("open cyclopentadienyl") chemistry by preparation of the phenylmethallyl ("open indenyl") ligand oInd(Me). The reaction of its potassium salt K(oInd(Me)) with [(η(5)-C(5)Me(5))RuCl](4) afforded the sandwich complex [(η(5)-C(5)Me(5))Ru(η(5)-oInd(Me))] (1), which, upon treatment with PMe(3), CO, and 2,6-dimethylphenyl isocyanide (CN-o-Xy), easily underwent η(5)-η(3) hapticity interconversion and formed the complexes [(η(5)-C(5)Me(5))Ru(η(3)-oInd(Me))(L)] (2, L = PMe(3); 3, L = CO; 4, L = CN-o-Xy). In these complexes, the η(3)-bound phenylmethallyl ligand adopts an anti-conformation with regard to the relative positions of the phenyl and methyl substituents. For the PMe(3) complex anti-2, slow conversion to the syn-isomer was observed, and this equilibrium reaction was monitored by NMR spectroscopy at 50 °C to determine a first order rate constant of k(323 K) = 6.57 × 10(-6) (± 0.02 × 10(-6)) s(-1) and an activation barrier of ΔG° = 26.8 kcal mol(-1). DFT calculations afforded a stabilization of syn-2 and syn-3 by ΔG(298) = -1.54 and -1.74 kcal mol(-1) over the respective anti-isomer.     

Palladium-arene interactions in catalytic intermediates: an experimental and theoretical investigation of the soft rearrangement between eta1 and eta2 coordination modes

A series of dichloro-bridged arylbicycloheptylpalladium complexes have been synthesized and characterized by means of NMR spectroscopy. The compound [(C16H19)PdCl]2*CH2Cl2 with ortho and para methyl substituents at the arene has been characterized by means of X-ray diffraction techniques. The C(ipso) atom of the arene lies almost at the fourth planar coordination site of the metal [Pd-C(ipso) = 2.22(1) A (average)], and due to the arene's tilting, the substituted C(ortho) atom is relatively close to the metal atom [2.54(1) A (average)]. The coordinated C(ipso)-C(ortho) linkage, in a seemingly dihapto coordination, is anti with respect to the CH2 bridge of the bicycloheptyl unit. Variable-temperature NMR experiments for the para-substituted dimer 9 reveal restricted rotation of the two aryl groups about the corresponding C-C(ipso) bonds (DeltaE < or =17 kcal x mol(-1)). DFT-B3LYP calculations have been carried out on the known and similar monomer (phenylbicycloheptenyl)Pd(PPh3)I (4) and its related substituted derivatives. The essential results are as follows: (i) The potential energy surface for twisting the phenyl ring away from the symmetric eta(1) coordination in 4 is very flat (DeltaE < or = 1 kcal x mol(-1)) whereas an Atoms in Molecules analysis excludes the existence of an actual Pd-C(ortho) bond in the seemingly eta2-type conformer. (ii) Complete rotation of the unsubstituted phenyl ring is not facile but feasible. A significant strain affects the transition-state structure featuring a Pd-HC(aryl) agostic-type bond. The calculated destabilization of 10.3 kcal x mol(-1), with respect to the ground state, can be compared to the experimental barrier of the dimer 9. (iii) Various methyl-substituted derivatives of 4 have been optimized, and their structural and energetic trends are discussed. An almost ideal eta1 coordination is shown by the anti conformer of the C(ortho)-substituted complex due steric effects. For all of the other cases, a slipped eta2 coordination may be described. As a general conclusion, the unsaturated metal center receives pi electron density of the arene mainly through its C(ipso) atom. The effect may be slightly improved if the C(ortho) atom also gets closer to the metal, but in no case, does the slipped eta2 coordination seem to be crucial for the stability of the system.     

A redox-mediated molecular brake: dynamic NMR study of 2-[2-(methylthio)phenyl]isoindolin-1-one and S-oxidized counterparts

A redox-mediated molecular brake based on the sulfide-sulfoxide redox cycle is illustrated by modulation of the rotation rate of an N-Ar "shaft" by varying the oxidation state of sulfur in 2-[2-(sulfur-substituted)phenyl]isoindolin-1-ones. N-Ar rotational barriers in methylsulfinyl (2) and methylsulfonyl (3) derivatives (13.6 kcal mol(-1)) are approximately 5 kcal mol(-1) higher than sulfide 1. Rate reduction for N-Ar rotation is approximately 10(4) s(-1) (280 K) upon oxidation. Correlated N-pyramidalization/N-Ar rotation reduces the effectiveness of the brake by decreasing the energy barrier to N-Ar bond rotation.     

MINDO-SCF-MO-berechnung der cis-trans-isomerisierung von N-methyl- und N-phenylazomethin

MINDO/2-SCF-MO calculations for the ground state properties of N-methyl- and N-phenyl-azomethin have been carried out. The calculated rotation barrier for the methyl group in N-methyl-azomethin was 0·8 kcal/mol, the eclipsed conformation being most stable. The calculated rotation barrier about the CN bond in the protonated methylazomethin was 27·9 kcal/mol. MINDO/1-SCF-MO treatment for the N-inversion barrier of the unprotonated species yielded 13·00 kcal/mol. Similar MINDO/2 calculations for N-phenylazomethin yielded 4·0 kcal/mol for the rotation barrier of the phenyl ring around the CN= bond, the perpendicular conformation of the ring to the CNC plane being most stable. For the corresponding N protonated derivative the value 27·3 kcal/mol was calculated for the rotation barrier around the CN bond. MINDO/1 treatment yielded an inversion barrier of 14·0 kcal/mol for N-phenylazomethin.     

Degenerate molecular shuttles with flexible and rigid spacers

The preparation and dynamic behavior of degenerate rotaxane molecular shuttles are described in which a benzylic amide macrocycle moves back and forth between two naphthalimide-glycine units along a diphenylethyne spacer or an aliphatic spacer consisting of a C(9), C(12), or C(26) alkyl chain. Subtle differences in the (1)H NMR spectra of the rotaxanes can be related to the presence of conformers in which the macrocycle interacts simultaneously with both glycines, especially in the case of the C(9) spacer. The kinetic data of the shuttling behavior in the C(26) rotaxane were obtained from dynamic NMR spectroscopy. The Eyring activation parameters were found to be ΔH(?) = 10 ± 1 kcal mol(-1), ΔS(?) = -6.5 ± 2.0 cal mol(-1) K(-1), ΔG(?)(298) = 11.9 ± 0.2 kcal mol(-1). For the systems with the shorter spacers, the shuttling rates were higher. Also in the diphenylethyne, rotaxane shuttling is rapid on the NMR time scale, indicating that the rigid unit does not impose a large barrier to the translocation of the macrocycle.     

Addition of Pt(PBu(t)(3)) groups to Ru(5)(CO)(12)(eta(6)-C(6)H(6))(mu(5)-C). Synthesis, structures, and dynamical activity

The reaction of Ru(5)(CO)(12)(eta(6)-C(6)H(6))(mu(5)-C), 7, with Pt(PBu(t)(3))(2) yielded two products Ru(5)(CO)(12)(eta(6)-C(6)H(6))(mu(6)-C)[Pt(PBu(t)(3))], 8, and Ru(5)(CO)(12)(eta(6)-C(6)H(6))(mu(6)-C)[Pt(PBu(t)(3))](2), 9. Compound 8 contains a Ru(5)Pt metal core in an open octahedral structure. In solution, 8 exists as a mixture of two isomers that interconvert rapidly on the NMR time scale at 20 degrees C, DeltaH() = 7.1(1) kcal mol(-1), DeltaS() = -5.1(6) cal mol(-)(1) K(-)(1), and DeltaG(298)(#) = 8.6(3) kcal mol(-1). Compound 9 is structurally similar to 8, but has an additional Pt(PBu(t)(3)) group bridging an Ru-Ru edge of the cluster. The two Pt(PBu(t)(3)) groups in 9 rapidly exchange on the NMR time scale at 70 degrees C, DeltaH(#) = 9.2(3) kcal mol(-)(1), DeltaS(#) = -5(1) cal mol(-)(1) K(-)(1), and DeltaG(298)(#) = 10.7(7) kcal mol(-1). Compound 8 reacts with hydrogen to give the dihydrido complex Ru(5)(CO)(11)(eta(6)-C(6)H(6))(mu(6)-C)[Pt(PBu(t)(3))](mu-H)(2), 10, in 59% yield. This compound consists of a closed Ru(5)Pt octahedron with two hydride ligands bridging two of the four Pt-Ru bonds.     

Cheletropic decomposition of cyclic nitrosoamines revisited: the nature of the transition states and a critical role of the ring strain

The cheletropic decompositions of 1-nitrosoaziridine (1), 1-nitroso-Delta(3)-pyrroline (2), 7-nitroso-7-azabicyclo[2.2. 1]hepta-2,5-diene (3), and 6-nitroso-6-azabicyclo[2.1.1]hexa-4-ene (4) have been studied theoretically using high level ab initio computations. Activation parameters of the decomposition of nitrosoaziridine 1 were obtained experimentally in heptane (DeltaH()(298) = 18.6 kcal mol(-)(1), DeltaS()(298) = -7.6 cal mol(-)(1) K(-)(1)) and methanol (20.3 kcal mol(-)(1), 0.3 cal mol(-)(1) K(-)(1)). Among employed theoretical methods (B3LYP, MP2, CCD, CCSD(T)//CCD), the B3LYP method in conjunction with 6-31+G, 6-311+G, and 6-311++G(3df,2pd) basis sets gives the best agreement with experimental data. It was found that typical N-nitrosoheterocycles 2-4 which have high N-N bond rotation barriers (>16 kcal mol(-)(1)) extrude nitrous oxide via a highly asynchronous transition state with a planar ring nitrogen atom. Nitrosoaziridine 1, with a low rotation barrier (<9 kcal mol(-)(1)) represents a special case. This compound can eliminate N(2)O via a low energy linear synperiplanar transition state (DeltaH()(298) = 20.6 kcal mol(-)(1), DeltaS()(298) = 2.5 cal mol(-)(1) K(-)(1)). Two higher energy transition states are also available. The B3LYP activation barriers of the cheletropic fragmentation of nitrosoheterocycles 2-4 decrease in the series: 2 (58 kcal mol(-)(1)) > 3 (18 kcal mol(-)(1)) > 4 (12) kcal mol(-)(1). The relative strain energies increase in the same order: 2 (0 kcal mol(-)(1)) < 3 (39 kcal mol(-)(1)) < 4 (52 kcal mol(-)(1)). Comparison of the relative energies of 2-4 and their transition states on a common scale where the energy of nitrosopyrroline 2 is assumed as reference indicates that the thermal stability of the cyclic nitrosoamines toward cheletropic decomposition is almost entirely determined by the ring strain.     

Reaction of phenyl radicals with acetylene: quantum chemical investigation of the mechanism and master equation analysis of the kinetics

The mechanism of the C(6)H(5) + C(2)H(2) reaction has been investigated by various quantum chemical methods. Electrophilic addition to the CC triple bond is found to be the only important mode of phenyl radical attack on acetylene. The initially formed chemically activated C(6)H(5)C(2)H(2) adducts may follow several isomerization pathways in competition with collisional stabilization and H-elimination. Thermochemistry of various decomposition and isomerization channels is evaluated by the G2M method. For key intermediates, the following standard enthalpies of formation have been deduced from isodesmic reactions: 94.2 +/- 2.0 kcal/mol (C(6)H(5)CHCH), 86.4 +/- 2.0 kcal/mol (C(6)H(5)CCH(2)), and 95.5 +/- 1.8 kcal/ mol (o-C(6)H(4)C(2)H(3)). The accuracy of theoretical predictions was examined through extensive comparisons with available experimental and theoretical data. The kinetics and product branching of the C(6)H(5) + C(2)H(2) reaction have been evaluated by weak collision master equation/Rice-Ramsperger-Kassel-Marcus (RRKM) analysis of the truncated kinetic model including only kinetically important transformations of the isomeric C(8)H(7) radicals. Available experimental kinetic data can be quantitatively reproduced by calculation with a minor adjustment of the C(6)H(5) addition barrier from 3.7 to 4.1 kcal/mol. Our predicted total rate constant, k(R1) = (1.29 x 10(10))T(0.834) exp(-2320/T) cm(3) mol(-)(1) s(-)(1), is weakly dependent on P and corresponds to the phenylation process under combustion conditions (T > 1000 K).     

NH tautomerism in the natural chlorin derivatives

The NH tautomerism of five Mg-free chlorophyll a and b derivatives 2-6 was studied utilizing NMR spectroscopy and molecular modeling. The results from the dynamic NMR measurements of the chlorins revealed that substituent effects contribute crucially to the free energy of activation (DeltaG(double dagger)) in the NH tautomeric processes. An intermediate tautomer for the total tautomeric NH exchange in a chlorin was observed for the first time, when the (1)H NMR spectra of chlorin e(6) TME (3) and rhodin g(7) TME (4) (TME = trimethyl ester) were measured at lower temperatures. The lower energy barriers (DeltaG(1)(double dagger)) obtained for the formation of the intermediate tautomers of 3 and 4, assigned to the N(22)-H, N(24)-H trans-tautomer, were 10.8 and 10.6 kcal/mol, respectively. The energy barrier (DeltaG(2)(double dagger) value) for the total tautomeric NH exchange in the five chlorins was found to vary from 13.6 kcal/mol to values higher than 18 kcal/mol. The lowest DeltaG(2)(double dagger) value (13.6 kcal/mol) was obtained for rhodochlorin XV dimethyl ester (2), which was the only chlorophyll derivative lacking the C(15) substituent. In the case of chlorins 4 and 5, the steric crowding around the methoxycarbonylmethyl group at C(15) raised the DeltaG(2)(double dagger) activation free-energy to 17.1 kcal/mol. However, the highest energy barrier with DeltaG(2)(double dagger) > 18 kcal/mol was observed for the NH exchange of pyropheophorbide a methyl ester (6), possessing the macrocycle rigidifying isocyclic ring E. Our results demonstrate that the steric strain, arising either from the steric crowding around the bulky substituent at C(15) or the macrocycle rigidifying isocyclic ring E, slows down the NH tautomeric process. We suggest that deformations in the chlorin skeleton are closely connected to the NH tautomeric exchange and that the exchange occurs by a stepwise proton-transfer mechanism via a hydrogen bridge.     

The rate-determining step in the rhodium-xantphos-catalysed hydroformylation of 1-octene

The rate-determining step in the hydroformylation of 1-octene, catalysed by the rhodium-Xantphos catalyst system, was determined by using a combination of experimentally determined (1)H/(2)H and (12)C/(13)C kinetic isotope effects and a theoretical approach. From the rates of hydroformylation and deuterioformylation, a small (1)H/(2)H isotope effect of 1.2 was determined for the hydride moiety of the rhodium catalyst. (12)C/(13)C isotope effects of 1.012(1) and 1.012(3) for the alpha-carbon and beta-carbon atoms of 1-octene were determined, respectively. Both quantum mechanics/molecular mechanics (QM/MM) and full quantum mechanics calculations were carried out on the key catalytic steps, for "real-world" ligand systems, to clarify whether alkene coordination or hydride migration is the rate-determining step. Our calculations (21.4 kcal mol(-1)) quantitatively reproduce the experimental energy barrier for CO dissociation (20.1 kcal mol(-1)) starting at the (bisphosphane)RhH(CO)(2) resting state. The barrier for hydride migration lies 3.8 kcal mol(-1) higher than the barrier for CO dissociation (experimentally determined trend approximately 3 kcal mol(-1)). The computed (1)H/(2)H and (12)C/(13)C kinetic isotope effects corroborate the results of the energy analysis.     

Structures, internal rotor potentials, and thermochemical properties for a series of nitrocarbonyls, nitroolefins, corresponding nitrites, and their carbon centered radicals

Structures, enthalpy (Δ(f)H°(298)), entropy (S°(T)), and heat capacity (C(p)(T)) are determined for a series of nitrocarbonyls, nitroolefins, corresponding nitrites, and their carbon centered radicals using the density functional B3LYP and composite CBS-QB3 calculations. Enthalpies of formation (Δ(f)H°(298)) are determined at the B3LYP/6-31G(d,p), B3LYP/6-31+G(2d,2p), and composite CBS-QB3 levels using several work reactions for each species. Entropy (S) and heat capacity (C(p)(T)) values from vibration, translational, and external rotational contributions are calculated using the rigid-rotor-harmonic-oscillator approximation based on the vibration frequencies and structures obtained from the density functional studies. Contribution to Δ(f)H(T), S, and C(p)(T) from the analysis on the internal rotors is included. Recommended values for enthalpies of formation of the most stable conformers of nitroacetone cc(═o)cno2, acetonitrite cc(═o)ono, nitroacetate cc(═o)no2, and acetyl nitrite cc(═o)ono are -51.6 kcal mol(-1), -51.3 kcal mol(-1), -45.4 kcal mol(-1), and -58.2 kcal mol(-1), respectively. The calculated Δ(f)H°(298) for nitroethylene c═cno2 is 7.6 kcal mol(-1) and for vinyl nitrite c═cono is 7.2 kcal mol(-1). We also found an unusual phenomena: an intramolecular transfer reaction (isomerization) with a low barrier (3.6 kcal mol(-1)) in the acetyl nitrite. The NO of the nitrite (R-ONO) in CH(3)C(═O')ONO moves to the C═O' oxygen in a motion of a stretching frequency and then a shift to the carbonyl oxygen (marked as O' for illustration purposes).     

DFT study on hydroxy acid-lactone interconversion of statins: The case of fluvastatin

Fluvastatin is a member of the HMG-CoA reductase inhibitor family of drugs, commonly referred to as statins. It is generally known that, under physiological conditions, statins are susceptible to pH-dependent interconversion between their active (hydroxy acid) and inactive (lactone) forms. The mechanism of this interconversion, under both acidic and basic conditions, was investigated theoretically using the density functional theory (DFT) method. Regardless of the conditions, the lactone form was always higher in energy by 6-19 kcal mol(-1). However, under basic conditions, the activation barrier for the hydrolysis was significantly lower (9 kcal mol(-1)) than for the reverse reaction (28 kcal mol(-1)), making the lactone form unstable. The activation barriers under acidic conditions were of comparable height in both directions (22 and 28 kcal mol(-1)), making the occurrence of both forms equally probable. Due to the high activation barrier (>40 kcal mol(-1)), a one-step, direct interconversion between the two forms turned out to be unfavourable. Moreover, the potential energy surface of fluvastatin was briefly inspected, revealing relatively small energetic differences (<5 kcal mol(-1)) between the key conformers.     

Computational investigation of hydrogen abstraction from 2-aminoethanol by the 1,5-dideoxyribose-5-yl radical: a model study of a reaction occurring in the active site of ethanolamine ammonia lyase

Hydrogen abstraction from 2-aminoethanol by the 5'-deoxyadenosyl radical, which is formed upon Co--C bond homolysis in coenzyme B(12), was investigated by theoretical means with employment of the DFT (B3LYP) and ab initio (MP2) approaches. As a model system for the 5'-deoxyadenosyl moiety the computationally less demanding 1,5-dideoxyribose was employed; two conformers, which differ in ring conformation (C2- and C3-endo), were considered. If hydrogen is abstracted from "free" substrate by the C2-endo conformer of the 1,5-dideoxyribose-5-yl radical, the activation enthalpy is 16.7 kcal mol(-1); with the C3-endo counterpart, the value is 17.3 kcal mol(-1). These energetic requirements are slightly above the activation enthalpy limit (15 kcal mol(-1)) determined experimentally for the rate-determining step of the sequence, that is, hydrogen delivery from 5'-deoxyadenosine to the product radical. The activation enthalpy is lower when the substrate interacts with at least one amino acid from the active site. According to the computations, when a His model system partially protonates the substrate the activation enthalpy is 4.5 kcal mol(-1) for the C3-endo conformer and 5.8 kcal mol(-1) for the C2-endo counterpart. As hydrogen abstraction from the fully as well as the partially protonated substrate is preceded by the formation of quite stable encounter complexes, the actual activation barriers are around 13-15 kcal mol(-1). A synergistic interaction of 2-aminoethanol with two amino acids where His partially protonates the NH(2) group and Asp partially deprotonates the OH group of the substrate results in an activation enthalpy of 12.4 kcal mol(-1) for the C3-endo conformer and 13.2 kcal mol(-1) for the C2-endo counterpart. However, if encounter complexes exist in the active site, the actual activation barriers are much higher (>25 kcal mol(-1)) than that reported for the rate-determining step. These findings together with previous computations suggest that the energetics of the initial hydrogen abstraction decrease with an interaction of the substrate with only a protonating auxiliary, but for the rearrangement of the radical the synergistic effects of two auxiliaries are essential to pull the barrier below the limit of 15 kcal mol(-1).     

Gas-phase acidity studies of multiple sites of adenine and adenine derivatives

The acidities of multiple sites in the purine nucleobase adenine (1) and adenine alkyl derivatives 9-ethyladenine (2), 3-methyladenine (3), 1-methyladenine (4), and N,N-dimethyladenine (5) have been investigated for the first time, using computational and experimental methods to provide an understanding of adenine reactivity. We have previously measured two acidic sites on adenine, with the N9 site being 19 kcal mol(-)(1) more acidic than the N10 site (333 +/- 2 versus 352 +/- 4 kcal mol(-)(1), respectively). In this work, we have established that 9-ethyladenine has two sites more acidic than water: the N10 (352 +/- 4 kcal mol(-)(1)) and the C8 (374 +/- 2 kcal mol(-)(1)). We have likewise measured two acidities for 3-methyladenine, the N10 (347 +/- 4 kcal mol(-)(1)) and the C2 (370 +/- 3 kcal mol(-)(1)). For 1-methyladenine and N,N-dimethyladenine, we measure the N9H acidity to be 331 +/- 2 and 333 +/- 2 kcal mol(-)(1), respectively. We believe that the bracketing of only one site for the latter species is a kinetic effect, which we discuss further in the paper. Computationally, we have found the interesting result that some of the vinylic C-H sites in these purine bases are predicted to be much more acidic than water (DeltaH(acid) = 390.7 kcal mol(-)(1)) in the gas phase, on the order of 373 kcal mol(-)(1). The acidic vinylic C-H sites are always adjacent to an N-R group, and this pattern is maintained regardless of whether the site is on the five- or six-membered ring of the purine. Vinylic C-H sites elsewhere on the purine have calculated acidities of about 400 kcal mol(-)(1). The differing acidities are interpreted through electrostatic potential calculations. We also relate our results to the intriguing biochemical decarboxylation of orotate ribose monophosphate, which involves a vinylic anion adjacent to an N-R group; this decarboxylation is the last step in the de novo biosynthesis of pyrimidine nucleotides, and the enzyme that catalyzes the reaction, orotate ribose monophosphate decarboxylase, has been the subject of intense study recently, as its mechanism remains elusive.     

Synthesis,structure, and dynamic behavior of cyclopentadienyl-lithium, -sodium,and -potassium annelated with bicyclo[2.2.2]octene units: a systematic study on site exchange of alkali metals on a cyclopentadienyl ring in tetrahydrofuran

Novel cyclopentadienyl (Cp)-alkali metal complexes 1-M and 2-M (M = Li, Na, K), in which the Cp ring is annelated with two bicyclo[2.2.2]octene units and substituted with a phenyl group for 1 and a tert-butyl group for 2, were synthesized, and their structures and dynamic behaviors were investigated by means of X-ray crystallography, dynamic (13)C NMR, and DFT calculations. The X-ray crystallography results indicated that 1-Li, 1-Na, and 2-Na form monomeric contact ion pairs (CIP) with three THF molecules coordinated to the metal atom. Also, in THF-d(8), all of the 1-M and 2-M form monomeric CIP in the ground state. However, variable-temperature (13)C NMR measurements of 1-M and 2-M in THF-d(8) demonstrated dynamic behavior in which the metal ion exchanges positions between the upper and lower faces of the Cp ring. From a study of the concentration dependence of the dynamic behavior, the exchange was found to proceed principally as an intramolecular process at concentration ranges lower than 0.2 M. The experimentally observed deltaG values for the intramolecular exchange process for all the 1-M and 2-M (except for 2-Li, whose intramolecular process was too slow to observe) were found to be quite similar in THF-d(8) solution and to fall within the range of 12-14 kcal mol(-)(1). Within this range, a tendency was observed for the deltaG values to increase as the size of the metal decreased. Theoretical calculations (B3LYP/6-31G(d)) afforded considerably large values as the gas-phase dissociation energy for 1-M (162.7 kcal mol(-)(1) for M = Li; 131.6 kcal mol(-)(1) for M = Na; 110.9 kcal mol(-)(1) for M = K) and for 2-M (170.0 kcal mol(-)(1) for M = Li; 137.5 kcal mol(-)(1) for M = Na; 115.4 kcal mol(-)(1) for M = K). These values should be compensated for by a decrease in the solvation energies for the metal ions with increasing size, as exemplified by the calculated solvation energy for M(+)(Me(2)O)(4), which serves as a model for metal ions solvated with four molecules of THF (-122.9 kcal mol(-)(1) for M = Li; -94.7 kcal mol(-)(1) for M = Na; -67.7 kcal mol(-)(1) for M = K). This compensation results in a small difference in the overall energy for dissociation of 1-M or 2-M in ethereal solutions, thus supporting the similar deltaG values observed for the intramolecular metal exchange.     

Reactions of vinyl acetate and vinyl trifluoroacetate with cationic diimine Pd(II) and Ni(II) alkyl complexes: identification of problems connected with copolymerizations of these monomers with ethylene

Vinyl acetate (VA) and vinyl trifluoroacetate (VA(f)) react with [(NwedgeN)Pd(Me)(L)][X] (M = Pd, Ni, (NwedgeN) = N,N'-1,2-acenaphthylenediylidene bis(2,6-dimethyl aniline), Ar(f) = 3,5-trifluoromethyl phenyl, L = Ar(f)CN, Et2O; X = B(Ar(f))4-, SbF6-) to form pi-adducts 3 and 5 at -40 degrees C. Binding affinities relative to ethylene have been determined. Migratory insertion occurs in a 2,1 fashion (DeltaG++ = 19.4 kcal/mol, 0 degrees C for VA, and 17.4 kcal/mol, -40 degrees C for VA(f)) to yield five-membered chelate complexes [(NwedgeN)Pd(kappa2-CH(Et)(OC(O)-CH3))]+, 4, and [(NwedgeN)Pd(kappa2-CH(Et)(OC(O)CF3))]+, 6. When VA is added to [(NwedgeN)Ni(CH3)]+, an equilibrium mixture of an eta2 olefin complex, 8c, and a kappa-oxygen complex, 8o, results. Insertion occurs from the eta2 olefin complex, 8c (DeltaG++ = 15.5 kcal/mol, -51 degrees C), in both a 2,1 and a 1,2 fashion to generate a mixture of five- and six-membered chelates, 9(2,1) and 9(1,2). VA(f) inserts into the Ni-CH3 bond (-80 degrees C) to form a five-membered chelate with no detectable intermediate. Thermolysis of the Pd chelates results in beta-acetate elimination from 4 (DeltaG++ = 25.5 kcal/mol, 60 degrees C) and beta-trifluoroacetate elimination from 6 (DeltaG = 20.5 kcal/mol, 10 degrees C). The five-membered Ni chelate, 9(2,1), is quite stable at room temperature, but the six-membered chelate, 9(1,2), undergoes beta-elimination at -34 degrees C. Treatment of the OAc(f) containing Pd chelate 6 with ethylene results in complete opening to the pi-complex [(NwedgeN)Pd(kappa2-CH(Et)(OAc(f)))(CH2CH2)]+ (OAc(f) = OC(O)CF3), 18, while reaction of the OAc containing Pd chelate 4 with ethylene establishes an equilibrium between 4 and the open form 16, strongly favoring the closed chelate 4 (DeltaH = -4.1 kcal/mol, DeltaS = -23 eu, K = 0.009 M(-1) at 25 degrees C). The open chelates undergo migratory insertion at much slower rates relative to those of the simple (NwedgeN)Pd(CH3)(CH2CH2)+ analogue. These quantitative studies provide an explanation for the behavior of VA and VA(f) in attempted copolymerizations with ethylene.