Search PubMed⌕ Search

Biomedical subjects

Herbert Mayr

Publications and source records attributed to Herbert Mayr.

At least 19 recordsLinked to original sources
PubMed2007

Nucleophilicities and carbon basicities of pyridines.

Rate and equilibrium constants for the reactions of pyridines with donor-substituted benzhydrylium ions have been determined spectrophotometrically. The correlation equation log k(20 degrees C)=s(N+E), in which s and N are nucleophile-specific parameters and E is an electrophile-specific parameter, has been used to determine the nucleophilicity parameters of various pyridines in CH(2)Cl(2) and aqueous solution and to compare them with N of other nucleophiles. It is found that the nucleophilic organocatalyst 4-(dimethylamino)pyridine (DMAP) and tertiary phosphanes have comparable nucleophilicities and carbon basicities despite widely differing Brønsted basicities. For that reason, these reactivity parameters are suggested as guidelines for the development of novel organocatalysts. The Marcus equation is employed for the determination of the intrinsic barriers of these reactions.

Journal Article↗
PubMed2006

Nucleophilic reactivities of indoles.

The kinetics of the coupling of indole (1a), N-methylindole (1b), 5-methoxyindole (1c), and 5-cyanoindole (1d) with a set of reference benzhydryl cations have been investigated in acetonitrile and/or dichloromethane. The second-order rate constants for the reactions correlate linearly with the electrophilicity parameter E of the benzhydryl cations. This allows the determination of the reactivity parameters, N and s, characterizing the nucleophilicity of 1a-d according to the linear free enthalpy relationship log k(20 degrees C) = s(N + E) (Acc. Chem. Res. 2003, 36, 66). The nucleophilicity parameters thus defined describe nicely the reactions of 1a-d with 4,6-dinitrobenzofuroxan (2), a neutral superelectrophilic heteroaromatic whose electrophilicity (E) has been recently determined. On this ground, the kinetics of the coupling of 2 with a large variety of indole structures have been studied in acetonitrile, leading to a ranking of this family of pi-excessive carbon nucleophiles over a large domain of the nucleophilicity scale N. Importantly, two linear and parallel correlations are obtained on plotting the measured N values versus the pK(a)(H(2)O) values for protonation at C-3 of 5-X-substituted indoles and 5-X-substituted 2-methylindoles, respectively. This splitting reveals that the presence of the 2-methyl group causes steric hindrance to the approach of 2 from the adjacent C-3 position of an indole structure. The N vs pK(a)(H(2)O) correlation for 5-X-substituted indoles is used for a rapid determination of the C-3 basicity of indoles whose acidity constants cannot be measured through equilibrium studies in strongly acidic aqueous media.

Indoles↗
PubMed2006

The reactivity-selectivity principle: an imperishable myth in organic chemistry.

The reactivity-selectivity principle (RSP), once a tenet of organic chemistry, eroded during the 1970s and was more or less abandoned by 1980. Although it has been clear for more than 25 years that a decrease in selectivity with increasing reactivity can only be expected with certainty if diffusion control is approached, the RSP has survived as an intuitively appealing rule. This Minireview shows why selectivity cannot generally decrease with increasing reactivity and highlights the weaknesses of the theoretical foundations of the RSP.

Journal Article↗
PubMed2006

Kinetics of the solvolyses of benzhydryl derivatives: basis for the construction of a comprehensive nucleofugality scale.

A series of 21 benzhydrylium ions (diarylmethylium ions) are proposed as reference electrofuges for the development of a general nucleofugality scale, where nucleofugality refers to a combination of leaving group and solvent. A total of 167 solvolysis rate constants of benzhydrylium tosylates, bromides, chlorides, trifluoroacetates, 3,5-dinitrobenzoates, and 4-nitrobenzoates, two-thirds of which have been determined during this work, were subjected to a least-squares fit according to the correlation equation log k(25 degrees C) = sf(Nf + Ef), where sf and Nf are nucleofuge-specific parameters and Ef is an electrofuge-specific parameter. Although nucleofuges and electrofuges characterized in this way cover more than 12 orders of magnitude, a single set of the parameters, namely sf, Nf, and Ef, is sufficient to calculate the solvolysis rate constants at 25 degrees C with an accuracy of +/-16 %. Because sf approximately 1 for all nucleofuges, that is, leaving group/solvent combinations, studied so far, qualitative discussions of nucleofugality can be based on Nf.

Benzhydryl Compounds↗
PubMed2006

How fast do R-X bonds ionize? A semiquantitative approach.

The correlation equation log k(25 degrees C) = sf(Nf + Ef), where sf and Nf are nucleofuge-specific parameters referring to leaving group/solvent combinations and Ef are electrofuge-specific parameters referring to the incipient carbocation R+, are used to predict ionization rate constants of alkyl derivatives R--X. We show how to employ the Ef parameters of reference electrofuges and the sf and Nf parameters of reference nucleofuges reported in the preceding article for determining further sf, Nf, and Ef parameters. Since sf is usually close to 1.0, one comes to the semiquantitative rule that at 25 degrees C, compounds R--X for which Nf + Ef>-2 will solvolyze with half-lives of less than a minute, while the solvolysis half-lives will exceed 1 month if Nf + Ef<-6.5.

Bromides↗
PubMed2006

Ability of neuron-specific enolase to predict survival to hospital discharge after successful cardiopulmonary resuscitation.

BACKGROUND: Accurate prediction of survival to hospital discharge in patients who achieve return of spontaneous circulation after cardiopulmonary resuscitation (CPR) has significant ethical and socioeconomic implications. We investigated the prognostic performance of serum neuron-specific enolase (NSE), a biochemical marker of ischemic brain injury, after successful CPR. METHODS: In-hospital or out-of-hospital patients with nontraumatic normothermic cardiac arrest who achieved return of spontaneous circulation (ROSC) following at least 5 minutes of CPR were eligible. Neuron-specific enolase levels were assessed immediately, 6 hours, 12 hours and 2 days after ROSC. Subjects were followed to death or hospital discharge. RESULTS: Seventeen patients (7 men, 10 women) were enrolled during a 1-year period. Median (range) NSE levels in survivors and non-survivors respectively were as follows: immediately after ROSC: 14.0 microg/L (9.1-51.4 microg/L) versus 25.9 microg/L (10.2-57.5 microg/L); 6 hours after ROSC: 15.2 microg/L (9.7-30.8 microg/L) versus 25.6 microg/L (12.7-38.2 microg/L); 12 hours after ROSC: 14.0 microg/L (8.6-32.4 microg/L) versus 28.5 microg/L (11.0-50.7 microg/L); and 48 hours after ROSC: 13.1 microg/L (7.8-29.5 microg/L) versus 52.0 microg/L (29.1-254.0 microg/L). Non-survivors had significantly higher NSE levels 48 hours after ROSC than surivors (p = 0.04) and showed a trend toward higher values during the entire time course following ROSC. An NSE concentration of >30 microg/L 48 hours after ROSC predicted death with a high specificity (100%: 95% confidence interval [CI] 85%-100%), and a level of 29 microg/L or less at 48 hours predicted survival with a high specificity (100%: 95% CI 83%-100%). CONCLUSIONS: Serum NSE levels may have clinical utility for the prediction of survival to hospital discharge in patients after ROSC following CPR over 5 minutes in duration. This study is small, and our results are limited by wide confidence intervals. Further research on ability of NSE to facilitate prediction and clinical decision-making after cardiac arrest is warranted.

Adult↗
PubMed2005

The DMAP-catalyzed acetylation of alcohols--a mechanistic study (DMAP = 4-(dimethylamino)pyridine).

The acetylation of tert-butanol with acetic anhydride catalyzed by 4-(dimethylamino)pyridine (DMAP) has been studied at the Becke3 LYP/6-311 + G(d,p)//Becke3 LYP/6-31G(d) level of theory. Solvent effects have been estimated through single-point calculations with the PCM/UAHF solvation model. The energetically most favorable pathway proceeds through nucleophilic attack of DMAP at the anhydride carbonyl group and subsequent formation of the corresponding acetylpyridinium/acetate ion pair. Reaction of this ion pair with the alcohol substrate yields the final product, tert-butylacetate. The competing base-catalyzed reaction pathway can either proceed in a concerted or in a stepwise manner. In both cases the reaction barrier far exceeds that of the nucleophilic catalysis mechanism. The reaction mechanism has also been studied experimentally in dichloromethane through analysis of the reaction kinetics for the acetylation of cyclohexanol with acetic anhydride, in the presence of DMAP as catalyst and triethylamine as the auxiliary base. The reaction is found to be first-order with respect to acetic anhydride, cyclohexanol, and DMAP, and zero-order with respect to triethyl amine. Both the theoretical as well as the experimental studies strongly support the nucleophilic catalysis pathway.

Journal Article↗
PubMed2005

Kinetics of the reactions of halide anions with carbocations: quantitative energy profiles for s(n)1 reactions.

Rate constants for the reactions of Laser flash photolytically generated benzhydrylium ions (diarylcarbenium ions) with halide ions have been determined in various solvents, including neat and aqueous acetonitrile as well as some alcohols. Substitution of the rate constants into the correlation equation log k = s(N + E) yields the nucleophilicity parameters N for the halide ions in different solvents. Linear correlations with negative slopes are found between the nucleophilicity parameters N for Cl(-) and Br(-) in different solvents and the solvent ionizing powers Y of the corresponding solvents. Increasing halide solvation reduces the rates of carbocation/chloride combinations by approximately half as much as it increases the rates of ionizations of benzhydryl chlorides. Comparison of the solvent dependent nucleophilicity parameters N of halide anions and the nucleophilicity parameters N(1) for solvents yields a quantitative prediction of common ion rate depression, as demonstrated by the analysis of a variety of literature reported mass-law constants alpha. Combination of the rate constants for the reactions of benzhydrylium ions with halide ions (k(-)()(1)) reported in this work with the ionization constants of benzhydryl halides (k(1)) and the recently reported rate constants for the reactions of benzhydrylium ions with solvents (k(2)) yields complete quantitative free energy profiles for solvolysis reactions. The applicability of Hammond's postulate for interpreting solvolysis reactions can thus be examined quantitatively.

Journal Article↗
PubMed2005

Rates and equilibria of the reactions of tertiary phosphanes and phosphites with benzhydrylium ions.

The kinetics of the reactions of benzhydrylium ions and quinone methides with eight tertiary phosphanes and two phosphites were investigated photometrically. The nucleophilicity parameters N and slope parameters s of these nucleophiles were derived according to the equation log k(20 degrees C) = s(N + E). Correlations of the nucleophilicity parameters N with pK(Ha) and sigma(p) values as well as with the rate constants of reactions with other electrophiles are discussed. In some cases, equilibrium constants for the formation of phosphonium ions were measured, which allow one to determine the Marcus intrinsic barriers of DeltaG(0) (not equal) = 58 kJ mol(-1) for the reactions of triarylphosphanes with benzhydrylium ions. The N parameters [5.51 for P(OPh)3, 10.36 for P(OBu)3, 14.33 for PPh3, 15.49 for PBu3, 18.39 for P(4-Me2NC6H4)3] are compared with the reactivities of other classes of nucleophiles (see, www.cup. uni-muenchen.de/oc/mayr).

Benzhydryl Compounds↗
PubMed2004

Nucleophilicities of nitroalkyl anions.

The kinetics of the reactions of eight nitroalkyl anions (nitronate anions) with benzhydrylium ions and quinone methides in DMSO and water were investigated photometrically. The second-order rate constants were found to follow a Ritchie constant selectivity relationship with slightly smaller selectivities than those observed previously for other carbanions and O or N nucleophiles. Evaluation of the kinetic data by the correlation equation log k (20 degrees C) = s(N + E) yields the nucleophilicity parameters (N), which allow a comparison of the nucleophilicities of nitronates with those of other classes of compounds. Although the aliphatic nitronates 1a-c are more nucleophilic than the aromatic representatives 1d-h in DMSO, hydration reduces the nucleophilicities of aliphatic nitronates by a factor of 1 million, which is considerably greater than the reduction of the reactivities of the aromatic nitronates with the consequence that aromatic nitronates are more nucleophilic in water than aliphatic ones. The nucleophilic reactivities of nitronates are only slightly affected by substituent variation in DMSO and even less so in aqueous solution, which is considered to be the reason for the unusual rate equilibrium relationships, the so-called nitroalkane anomaly. Outer-sphere electron transfer does not occur in any of the reactions that were investigated.

Journal Article↗
PubMed2004

Solvent nucleophilicity.

The rates of the reactions of benzhydrylium ions (diarylcarbenium ions) with solvent mixtures of variable composition (water/acetonitrile, methanol/acetonitrile, ethanol/acetonitrile, ethanol/water, and trifluoroethanol/water) have been determined photometrically by conventional UV-vis spectroscopy, stopped-flow methods, and laser flash techniques. It has been shown that the first-order rate constants follow the previously published relationship log k(20 degrees C) = s(N + E), where E is an empirical electrophilicity parameter, N is an empirical nucleophilicity parameter, and s is a nucleophile-specific slope parameter. From plots of log k versus E of the benzhydrylium ions are derived the solvent nucleophilicity parameters s and N, the latter of which are designated as N1 to emphasize that their use in the quoted correlation equation gives rise to first-order rate constants. A linear correlation between N1 and Kevill's solvent nucleophilicity NT based on S-methyldibenzothiophenium ions is reported, which allows one to interconvert the two sets of data. Because the N1 values are directly comparable to the previously reported nucleophilicity parameters N for pi-systems (www.cup.uni-muenchen.de/oc/mayr/), the systematic design of Friedel-Crafts reactions with solvolytically generated carbocations becomes possible.

Journal Article↗