Integrated NMR and Ab initio study of acetonitrile in zeolites: A reactive complex model of zeolite acidity

Experimental and theoretical methods have provided a detailed view of the mechanism of proton transfer from a zeolite to a weak base. The NMR behavior of acetonitrile in acidic zeolites differs significantly from that in superacid solution and implies a different structure for the protonated species. ¹³C and ¹H chemical shifts are strongly and reversibly temperature dependent for acetonitrile in zeolite HZSM-5 - in the high-temperature range used for most catalytic applications of zeolites. The experimental results were first used to propose a qualitative model in which progressive proton transfer occurs with increasing temperature, resulting in a partial charge on the nitrile carbon. Ab initio Hartree-Fock-Roothaan calculations using finite clusters to model the acid site were carried out to refine this model and test alternate hypotheses. The minimum energy conformation for the acetonitrile-zeolite cluster in a large channel is a hydrogen-bonded complex. The effects of increased temperature and reduced channel size were simulated by introducing constraints prior to the geometry optimization in a manner so as to sample higher energy conformations and close contact with the channel wall. Those calculations yielded a family of structures describing proton transfer from the zeolite to the weak base within the complex. Hydrogen-bonded acetonitrile bends at higher energies; for bend angles near 165°, the energies for zeolite protonation and N protonation cross. The accuracy of the calculated structures was tested by using ab initio methods to calculate the ¹H and ¹³C chemical shifts of the clusters and related models. Only bent structures accounted for the ¹³C shifts, and calculated ¹H shifts for the cluster models were in complete agreement with experiment. The (reversible) reaction between the Bronsted acid site and the weak base acetonitrile should be viewed as a cooperative or concerted process, rather than simple proton transfer from a superacid to a base. Changes in the structure of the base drive proton transfer as the complex moves along the reaction coordinate. The temperature-dependent NMR behavior of acetonitrile in various zeolites is sensitive to differences in acid strength and zeolite framework. Relative energies derived from Hartree-Fock-Roothaan calculations were used to construct potential wells for quasi-one-dimensional models of zeolites with different pore diameters. These models rationalize the different temperature dependence in the medium and large pore zeolites and suggest that confinement of the weak base near the acid site is an important aspect of reactivity in acidic zeolites. The integration of experiment and calculation demonstrated here is a more rigorous alternative to the use of qualitative chemical shift arguments to deduce structure, and it permits closure between theory and experiment

Risk assessment in immunotoxicology. II. Relationships between immune and host resistance tests

We have reported on the design and content of a screening battery using a 'tier' approach for detecting potential immunotoxic compounds in mice (Luster et al., Fundam. Appl. Toxicol., 10, 2-19, 1988). The data base generated from these studies, which consists of over 50 selected compounds, has heen collected and analyzed in an attempt to improve future testing strategies and provide information to aid in developing future quantitative risk assessment for immunotoxicity. In a recent study it was shown that as few as two or three immune parameters were needed to predict immunotoxicants in mice (Luster et al., Fundam. Appl. Toxicol., 18, 200-210, 1992). In particular, enumeration of lymphocyte populations and quantitation of the T-dependent antibody response were particularly beneficial. Furthermore, commonly employed apical measures (e.g., leukocyte counts, lymphoid organ weights) were fairly insensitive. The present analyses focus on the use of this data base to develop statistical models that examine the qualitative and quantitative relationship(s) between the immune function and host resistance tests. The conclusion derived from these analyses are: (1) A good correlation exists between changes in the immune tests and altered host resistance in that there were no instances where host resistance was altered without affecting an immune test(s). However, in some instances immune changes occurred without corresponding changes in host resistance. (2) No single immune test could be identified which was fully predictive for altered host resistance, although most assays were relatively good indicators (i.e., >70%). Several others, such as proliferative response to lipopolysaccharide and leukocyte counts, were found to be relatively poor indicators for host resistance changes. (3) The ability to resist infectious agent challenge is dependent upon the degrees of immunosuppression and the quantity of infectious agent administered. (4) Logistic and standard regression modeling using one extensive chemical data set from the immunosuppressive agent, cyclophosphamide, indicated that most immune function-host resistance relationships followed linear rather than linear-quadratic (threshold-like) models. For most of the relationships this could not be confirmed using a large chemical data set and, thus, a more mechanistically based approach for modeling will need to be developed. (5) Using this limited data set, methods were developed for modeling the precise quantitative relationships between changes in selected immune tests and host resistance tests