Symmetry of N-H-N hydrogen bonds in 1,8-bis(dimethylamino)naphthalene.H+ and 2,7-dimethoxy-1,8-bis(dimethylamino)naphthalene.H+.

In solution, are the hydrogen bonds in monoprotonated N,N,N',N'-tetramethyl-1,8-naphthalenediamines single- or double-well? To answer this question, isotopic perturbation of equilibrium is applied to a mixture of -d(0), -d(3), -d(6), -d(9), and -d(12) isotopologs. The N-methyls of the 2,7-dimethoxy analogue show intrinsic isotope shifts from the geminal CD(3) and from only one distant CD(3), an unusual stereochemical effect transmitted across the hydrogen bond. The (13)C NMR splittings and intensities at the various ring carbons of both ions are consistent with perturbation isotope shifts, intrinsic shifts, or a combination of both. The perturbation shifts mean that the protons reside in a double-minimum potential and that each ion is a pair of rapidly interconverting tautomers. The significance of this result for the role of low-barrier hydrogen bonds in enzyme-catalyzed reactions is discussed.

Is there stereoelectronic control in hydrolysis of cyclic guanidinium ions?

To assess stereoelectronic effects in the cleavage of tetrahedral intermediates, a series of five-, six-, and seven-membered cyclic guanidinium salts was synthesized. If stereoelectronic control by antiperiplanar lone pairs is operative, these are expected to hydrolyze with endocyclic C-N cleavage to acyclic ureas. However, hydrolysis in basic media produces mixtures of cyclic and acyclic products, as determined by 1H NMR analysis. The results show that in the six-membered ring antiperiplanar lone pairs provide a weak acceleration of the breakdown of the tetrahedral intermediate, but in five- and seven-membered rings there is no evidence for such acceleration, which instead can be provided by syn lone pairs.

Stereoelectronic control in addition of nucleophiles to an amidinium ion.

Nucleophilic addition to 1,3-dimethyl-5-phenyl-1,4,5,6-tetrahydropyrimidinium ion provides a quantitative measure of stereoelectronic control. This amidinium ion presents the nucleophile with two distinct paths for attack. Axial attack is favored by interaction between the orbital of the developing bond and antiperiplanar lone pairs on the nitrogens. Reaction of the amidinium salt with diverse nucleophiles (D(-), H3C(-), n-Bu(-), PhCH2(-), allyl(-), Ph(-), C5F6(-), CH2=CH(-), HC triple bond C(-), PhC triple bond C(-), CN(-)) produces mixtures of cis and trans stereoisomers. Both kinetic and thermodynamic product distributions were measured by 1H NMR, before and after acid-catalyzed equilibration. The values provide insight into the roles of steric and stereoelectronic forces at the transition state and in products. Stereoelectronic effects on reactivity are found to be weak (ca. 1 kcal/mol).

Symmetry of metal chelates.

Is a metal chelate symmetric, with the motion of the metal described by a single-well potential, or is it asymmetric, in a double-well potential? For hydrogen, this is the familiar question of the symmetry of a hydrogen bond. The molecular symmetry of MLn complexes (M = Li, Na, K, Al, Pd, Rh, Si, Sn, Ge, Sb, etc.; L is the anion of 3-hydroxy-2-phenylpropenal) in solution is now probed with the method of isotopic perturbation of equilibrium. A statistical mixture of 3-hydroxy-2-phenylpropenal-d0, -1-d, and -1,3-d2 was synthesized and converted to various metal complexes. Some complexes show two aldehydic signals, which means that their ligands are monodentate. For LiL, NaL, and KL, the 13C NMR isotope shifts, delta CH(D) - delta CH(H), for the aldehydic CH groups are small and negative, consistent with L- being a resonance hybrid. They are small and positive for AlL3, PdL2, Rh(CO)2L, SiX3L, SiL3+X-, (CF3)3GeL, SbCl4L, (EtO)4TaL, and (EtO)4NbL. The positive isotope shifts are unusual, but since they are small and temperature independent, they are intrinsic and indicate that these metal chelates are symmetric, as expected. Large positive isotope shifts, up to 400 ppb, are observed for Ph3GeL, Me3GeL, Ph2GeL2, Bu3SnL, and Ph4SbL. However, it is likely that these are monodentate complexes undergoing rapid metal migration, as judged from the X-ray crystal structures of Ph3SnL and Ph4SbL. NMR experiments indicate an intermolecular mechanism for exchange, which may be a biomolecular double metal transfer. It is remarkable that the isotope shifts in these five complexes demonstrate that they are asymmetric structures, even though they appear from other NMR evidence to be symmetric chelates.

"Strong" hydrogen bonds in chemistry and biology.

Hydrogen bonds are a key feature of chemical structure and reactivity. Recently there has been much interest in a special class of hydrogen bonds called "strong" or "low-barrier" and characterized by great strength, short distances, a low or vanishing barrier to hydrogen transfer, and distinctive features in the NMR spectrum. Although the energy of an ordinary hydrogen bond is ca 5 kcal mol-1, the strength of these hydrogen bonds may be > or = 10 kcal mol-1. The properties of these hydrogen bonds have been investigated by many experimental techniques, as well as by calculation and by correlations among those properties. Although it has been proposed that strong, short, low-barrier hydrogen bonds are important in enzymatic reactions, it is concluded that the evidence for them in small molecules and in biomolecules is inconclusive.

Multicomponent NMR titration for simultaneous measurement of relative pKaS.

An NMR titration method has been developed to simultaneously measure the difference in acid dissociation constants (delta pKa) of two or more compounds with high precision and accuracy. The delta pKa between the conjugate acids of the two stereoisomers of 4-tert-butylcyclohexylamine 1 was determined in a single 1H NMR titration experiment. A mixture of the two stereoisomers was titrated with DCI in a 3:1 (v/v) mixture of CD3OD/D2O. From the variations of the H1 chemical shifts the ratio of the acidity constants was determined. The trans stereoisomer 1t was found to be the more basic by 0.121 +/- 0.002 pK unit. A repeat titration in DMSO-d6 also found 1t to be the more basic, by 0.217 +/- 0.003 pK unit. The delta pKa between the two stereoisomers of 4-tert-butylcyclohexanecarboxylic acid 2 was determined in both of these solvents using 1H and 13C NMR. Thermodynamic parameters delta delta H degree and delta delta S degree were evaluated from the temperature dependence of delta pKa. To further demonstrate the utility of this method, the delta pKas of the conjugate acids of the four stereoisomers of 2-decalylamine 3 were determined in a single 1H NMR titration experiment. The cis,cis stereoisomer (3cc) was found to be the most basic, with the cis,trans (3ct), trans,cis (3tc), and trans,trans (3tt) less basic by 0.012 +/- 0.003, 0.037 +/- 0.004, and 0.141 +/- 0.005 pK unit, respectively. A second four-component titration was also performed with the two 4-tert-butylcyclohexylamines (1) and the two trans-2-decalylamines (3tc, 3tt).

Symmetries of hydrogen bonds in solution.

The nuclear magnetic resonance method of isotopic perturbation can distinguish between single- and double-well potentials in intramolecularly hydrogen-bonded monoanions of dicarboxylic acids. These are classic cases of a "strong," symmetric hydrogen bond in the crystal. The observed carbon-13 isotope shifts induced by the substitution of oxygen-18 demonstrate that these monoanions exist as a single symmetric structure in a nonpolar solvent but as two equilibrating tautomers in aqueous solution. The change is attributed to the disorder of the aqueous environment. These are simple counterexamples to the hope that the crystal structure reveals the actual molecular structure in aqueous solution.

Sexually abused and nonabused children's conceptions of personal body safety.

This study compared characteristics of abused and nonabused children's conceptions about personal body safety. A projective type vignette describing a personal body safety violation was read to 25 abused children entering a treatment program in eastern Washington and 25 nonabused children matched on sex, age, and grade in school. The children were asked questions about the vignette incident, and responses were compared between the abused and nonabused children. Significant differences were obtained between abused and nonabused children's conceptions of personal body safety with regard to their definitions of sexual abuse, descriptions of violators, and perceptions of consequences for the violator. Few significant differences were observed regarding conceptions of the victim, and no differences were observed on responses to two control vignettes depicting violations of traffic and school safety rules. Comparisons are made between both abused and nonabused children's understandings of the phenomenon. In addition, suggestions are offered for incorporating this information into sexual abuse prevention and treatment programs as well as future research.

Comparison of programs for teaching personal safety skills to preschoolers.

We compared the relative effectiveness of two educational approaches for teaching personal safety skills with 100 preschoolers. A behavioral skills training program was compared with a feelings-based program, which instructs children to trust their feelings when making safety decisions. Children's abilities to discriminate between appropriate- and inappropriate-touch requests, their prevention skills, and levels of emotional distress were assessed before, immediately, and one month after program participation. Parents and teachers were surveyed regarding children's reactions. Compared with a control presentation, both programs were effective in enhancing children's knowledge and prevention skills without making them fearful, suggesting that preschool children can benefit from such programs. However, children in the feelings-based program had difficulty recognizing the appropriateness of certain touch requests, suggesting that this approach may have limited utility with preschool-age children.

Rotation and solvation of ammonium ion.

From nitrogen-15 spin-lattice relaxation times and nuclear Overhauser enhancements, the rotational correlation time (c) for (15)NH(4)(+) was determined in a series of solvents. Values of (c) range from 0.46 to 20 picoseconds. The solvent dependence of (c) cannot be explained in terms of solvent polarity, molecular dipole moment, solvent basicity, solvent dielectric relaxation, or solvent viscosity. The rapid rotation and the variation with solvent can be accounted for by a model that involves hydrogen bonding of an NH proton to more than one solvent molecule in a disordered solvation environment.

An evaluation of side effects associated with participation in a child sexual abuse prevention program.

Parents of children who participated in a school-based sexual abuse prevention program were surveyed regarding their children's reactions to the program. In addition, children were asked to rate their fears of various people and situations both before and after participating in the program. No increases in fear ratings were observed, and parents reported no increased frequency of problematic behaviors. Fathers reported a significant decrease in total frequency of problem behaviors after the program. No parent reported the program had an overall negative effect on their child. Instead, the program stimulated discussion in the home regarding sexual abuse. This exchange of information was important, as results indicated more than one-half the parents had not discussed the topic with their child before the program. The results suggest sexual abuse prevention programs can be implemented effectively in schools without harming the children.

Protein pattern alterations in hippocampal and cortical cells as a function of training in rats.

The study reports changes in the protein pattern and incorporation of L-[U-14C]-leucine in brain cells of the hippocampus and sensorimotor cortex of rats. The following subcellular fractions were analyzed by SDS-acrylamide gel electrophoresis: plasma membranes, synaptosomal membranes and synaptic mitochondria. Recurring reversal training gave an increased synthesis of synaptosomal membrane proteins with mol. wt. 35,000-45,000 and 60,000 and 100,000 in trained animals compared to active controls. Lesser changes were observed in plasma membrane and synaptic mitochondria fractions. Of the brain areas studied, the hippocampal synaptosomal fraction showed an initial, temporary response, and the cortical cell fractions responded subsequently. Judged from the time sequence of the protein response, it seems that recurrent reversal training induces a change in synaptic protein towards higher molecular weights, suggesting that these changes reflect a modification of the distribution of synaptic protein.