Showing papers on "Steric effects published in 1997"
TL;DR: In this paper, a charge-transfer origin (λCT) analysis of the colored solutions revealed their charge transfer origin and provided quantitative information of the intermolecular association in the form of the KDA and eCT values for the formation and visualization, respectively, of different [D,A] complexes.
Abstract: Molecular association of various aromatic hydrocarbons (D, including sterically hindered donors) with a representative group of diverse acceptors (A = quinone, trinitrobenzene, tetracyanoethylene, tropylium, tetranitromethane, and nitrosonium) is visually apparent in solution by the spontaneous appearance of distinctive colors. Spectral (UV−vis) analyses of the colored solutions reveal their charge-transfer origin (λCT), and they provide quantitative information of the intermolecular association in the form of the KDA and eCT values for the formation and visualization, respectively, of different [D,A] complexes. Importantly, such measurements establish charge-transfer absorption to be a sensitive analytical tool for evaluating the steric inhibition of donor−acceptor association. For example, the steric differences among various hindered aromatic donors in their association with quinone are readily dramatized in their distinctive charge-transfer (color) absorptions and verified by X-ray crystallography of ...
259 citations
TL;DR: New insights are allowed into the molecular recognition processes of neutral guest and host substances, as well as further understanding of these processes in template synthesis, isomerism in catenanes, and the regioselectivity of the formation of catenane isomers.
Abstract: After Sauvage et al. and Stoddart et al. had developed the now commonly used and well-established catenane and rotaxane synthesis utilizing phenanthroline/Cu+ and bipyridinium/crown units, a new way to synthesize mechanical bonds was discovered in 1992—the synthesis of amide-linked catenanes and rotaxanes around a neutral template. The formation of the template, which leads to the host–guest bond, does not proceed by covalent or ionic interaction, but by weak supramolecular interactions, such as hydrogen bonding, π-stacking, π-donor–π-acceptor interaction, and steric complementarity. The simple synthetic units (arene dicarboxylic acid dichlorides and diamines) can be varied in an astonishing number of ways, few steps are required to obtain the target molecules, and the yields of these syntheses approach those of ordinary organic syntheses. After the preparation of [2]catenanes, it took only a few years to prepare [2]-, [3]-, and bis[2]-rotaxanes of the amide type. The introduction of sulfonamide groups enabled alkylation of the sulfonamide nitrogen atom, and this made chemical reactions with catenanes and rotaxanes feasible. Intra- and intermolecular connections of catenanes and rotaxanes were then possible, and a molecule with the topology of a “pretzel” has recently been prepared. This allowed new insights into the molecular recognition processes of neutral guest and host substances, as well as further understanding of these processes in template synthesis, isomerism in catenanes, and the regioselectivity of the formation of catenane isomers. Competitive binding studies of guest molecules in the cavity of concave receptors with more than one binding site can be perfomed. These studies might result in higher synthetic yields of molecules with mechanical bonds and lead to further progress in the development of supramolecular nanostructures and molecular switches.
254 citations
TL;DR: In this article, an ab initio procedure for extracting the Pauli exchange antisymmetry (steric) contributions to molecular potential energy in the framework of self-consistent field molecular orbital (SCFMO) theory is described.
Abstract: We describe an ab initio procedure for extracting the Pauli exchange antisymmetry (“steric”) contributions to molecular potential energy in the framework of self-consistent-field molecular orbital (SCFMO) theory. This “natural steric analysis” method is based on natural bond orbital (NBO) representation of the SCFMO wave function, which allows the steric exchange energy to be approximated as an energy difference between “preorthogonal” and final NBOs, analogous to the procedure of Sovers et al. [J. Chem. Phys. 49, 2592 (1965)]. We show how the total NBO steric exchange energy can in turn be approximated in terms of pairwise-additive interactions between localized bonding units, comparable to the empirical steric potentials of molecular mechanics models. The accuracy of NBO steric analysis is tested in applications to various rare-gas interactions (expected to be of pure steric exchange type), and excellent agreement is found with the full ab initio potential curves over a wide range of separations. Limitations of the simple pairwise-additive model of steric exchange interactions are noted and characterized.
248 citations
TL;DR: In this paper, the three isomers of diferrocenylbenzenes (ortho, 1o; meta, 1m; para, 1p) as well as 5-substituted derivatives of m-diferrocensylbenzene with R = NH2 (2), Cl (3), CH3 (4), CN (5), NO2 (6), and N(CH3)33+ (7) have been prepared.
Abstract: The three isomers of diferrocenylbenzenes (ortho, 1o; meta, 1m; para, 1p) as well as 5-substituted derivatives of m-diferrocenylbenzene with R = NH2 (2), Cl (3), CH3 (4), CN (5), NO2 (6), and N(CH3)33+ (7) have been prepared. Crystal structures of 1o, 3, and 5 have been solved. In 3 and 5, the cyclopentadienyl rings are nearly parallel to the benzene mean planes with angles ranging from 9.99(5)° to 14.74(5)°. One ferrocene group is above and the other below the mean molecular plane. For 1o, there is an important twist between the benzene and cyclopentadiene rings (68.6(8)° and 32.5(8)°) for steric reasons. Controlled potential electrolysis yields the mixed-valence ferrocene/ferrocenium species in comproportionation equilibrium with homovalent species. Intervalence transitions have been observed and corrected from comproportionation. From the intervalence band parameters, metal−metal couplings (Vab) are calculated using Hush's equation. The values are much higher for 1o (0.025 eV) and 1p (0.043 eV) than fo...
229 citations
TL;DR: In this article, a series of pseudotetrahedral complexes of the form Cu(NN)2+, where NN denotes a 1,10-phenanthroline ligand with alkyl substituents in the 2 and 9 positions and the counterion is PF6-.
Abstract: This investigation focuses on a series of pseudotetrahedral complexes of the form Cu(NN)2+, where NN denotes a 1,10-phenanthroline ligand with alkyl substituents in the 2 and 9 positions and the counterion is PF6-. In these copper(I) systems, steric effects are of considerable interest because the electronic configuration predisposes the reactive charge-transfer excited state to undergo a flattening distortion or to add a fifth ligand. Both effects lead to emission quenching and a shorter excited-state lifetime. Bulky substituents inhibit these processes, but the spatial distribution of the atoms involved is more important than the total molecular volume in determining the influence of a substituent. According to the results of this study, the effective size decreases in the following order: sec-butyl > neopentyl > n-octyl ≈ n-butyl > methyl. In conjunction with the electrochemical data, the absorption and the emission spectra reveal three kinds of steric effects: (1) Clashes between substituents on opp...
228 citations
TL;DR: In this article, a large-pore SAPO-5 and a medium-POR SAPO were synthesized using a hydrothermal method, and they were characterized by chemical analysis, XRD, SEM, IR, TPD of NH 3, and MAS NMR; Pt dispersion was measured by H 2 adsorption.
227 citations
TL;DR: In this article, the influence of reactant alignment on the rates of chemical reactions provided direct information concerning the atomic motions necessary for chemical transformation, and it was shown that at low collision energy, the dissociative adsorption of deuterium on the surface of copper has a much higher probability for broadside than for end-on collisions.
Abstract: Measurements of the influence of reactant alignment on the rates of chemical reactions provide direct information concerning the atomic motions necessary for chemical transformation. Data presented here show that at low collision energy, the dissociative adsorption of deuterium (D2) on the (111) surface of copper has a much higher probability for broadside than for end-on collisions. Furthermore, this steric preference is sensitive to the kinetic energy of the incident molecule, almost disappearing as the energy increases to 0.8 electron volt. This study shows that the dynamic conditions of a surface chemical reaction can profoundly influence the associated steric requirements.
188 citations
TL;DR: Consideration of the available structural data on chymotrypsin and other serine proteases, together with the high pK(a)s of the hemiketals formed with TFKs, suggests that LBHB formation in catalysis arises through a substrate-induced conformational transition leading to steric compression between His 57 and Asp 102.
Abstract: The basicities of the diad H57−D102 at Ne2 in the tetrahedral complexes of chymotrypsin with the peptidyl trifluoromethyl ketones (TFK) N-acetyl-l-Leu-dl-Phe-CF3 and N-acetyl-dl-Phe-CF3 have been studied by 1H-NMR. The protons bridging His 57 and Asp 102 in these complexes are engaged in low-barrier hydrogen bonds (LBHBs). In 1H-NMR spectra at pH 7.0, these protons appear at δ 18.9 and 18.6 ppm, and the pKas of the diads are 12.0 ± 0.2 and 10.8 ± 0.1, respectively. The difference indicates that removal of leucine from the second aminoacyl site S2 of chymotrypsin weakens the LBHB and decreases the basicity of the H57−D102 diad relative to the case in which S2 is occupied by leucine. Consideration of the available structural data on chymotrypsin and other serine proteases, together with the high pKas of the hemiketals formed with TFKs, suggests that LBHB formation in catalysis arises through a substrate-induced conformational transition leading to steric compression between His 57 and Asp 102. Because the N...
183 citations
147 citations
141 citations
TL;DR: In this paper, the effect of an â-heteroatom substituent on the enolate face selectivity of aldehyde electrophiles was investigated in a double-stereodifferentiating aldol reaction.
Abstract: In the addition of enol derivatives to â-alkoxy aldehydes, the influence of the â-heteroatom substituent may be regulated by the nature of the aldol process selected (eq 1). For example, good levels of 1,3-anti induction may be realized in the Lewis acid-promoted addition with enol silanes. In contrast, this same substituent possesses no control over the analogous enol borinate nucleophilic additions.2 We have speculated that the principal bias exerted by the â-alkoxy substituent is electrostatic in nature. Given the importance of these remote effects on the π-facial selectivity of aldehyde electrophiles, we have now probed the analogous polar effect of a â-heteroatom substituent on the enolate facial bias in these acetate aldol processes (eq 2).3,4 In this paper, methyl ketone enolates that undergo highly 1,5-diastereoselective aldol addition are identified, and the integration of this control element into double-stereodifferentiating aldol reactions is presented. This study was initiated with an examination of the aldol reactions of unsubstituted ketone enolates 1 (M ) TMS, Li, BR2) that contain a â-alkoxy substituent (Table 1). To isolate the contribution of electrostatic effects to the diastereoselectivity of these addition processes, enolates 1 were selected bearing â-substituents of similar steric size (-OCH2Ar vs -CH2CH2Ar) but different electronic properties. Unlike our previous study on 1,3induction (eq 1),2 the dialkylboron enolates5 displayed good levels of asymmetric induction with dihydrocinnamaldehyde, consistently favoring the 1,5-anti diol product 2 (Table 1, entries 1-5). Due to the similar steric requirements of the â-substituents, electrostatic effects might be at least partially responsible for enolate face selectivity. The enolate facial bias may be further enhanced by a decrease in reaction temperatures (Table 1, entry 5). In contrast to our previous study on 1,3induction (eq 1),2 the Lewis acid-mediated aldol reaction in this system demonstrated no asymmetric induction (Table 1, entry 6).6 Similarly, the aldol reactions of metal enolates capable of internal chelation with the â-heteroatom were also nonselective (Table 1, entry 7).7 (1) For general approaches to the synthesis of 1,3-diol relationships in conjunction with C-C bond formation see: (a) Rychnovsky, S. D.; Hoye, R. C. J. Am. Chem. Soc. 1994, 116, 1753-1765. (b) Mora, Y.; Asai, M.; Okumura, A.; Furukawa, H. Tetrahedron 1995, 51, 52995314. (c) Knochel, P.; Brieden, W.; Rozema, M. J.; Eisenberg, C. Tetrahedron Lett. 1993, 34, 5881-5884. (2) (a) Evans, D. A.; Duffy, J. L.; Dart, M. J. Tetrahedron Lett. 1994, 35, 8537-8540. (b) Evans, D. A.; Dart, M. J.; Duffy, J. L.; Yang, M. G. J. Am. Chem. Soc., 1996, 118, 4322-4343. (3) (a) Blanchette, M. A.; Malamas, M. S.; Nantz, M. H.; Roberts, J. C.; Somfai, P.; Whritenour, D. C.; Masamune, S. J. Org. Chem. 1989, 54, 2817-2825. (b) Seebach, D.; Misslitz, U.; Uhlmann, P. Angew. Chem., Int. Ed. Engl. 1989, 28, 472-473. (4) For 1,4-induction in acetate aldol reactions see: (a) Zibuck, R.; Liverton, N. J.; Smith, A. B. J. Am. Chem. Soc. 1986, 108, 2451-2453. (b) Braun, M. Angew. Chem., Int. Ed. Engl. 1987, 26, 24-37. (c) Paterson, I.; Goodman, J. M.; Isaka, M. Tetrahedreon Lett. 1989, 30, 7121-7124. (d) Trost, B. M.; Urabe, H. J. Org. Chem. 1990, 55, 39823983. (e) Roush, W. R.; Bannister, T. D. Tetrahedron Lett. 1992, 33, 3587-3590. (f) Lagu, B. R.; Liotta, D. C. Tetrahedron Lett. 1994, 35, 4485-4488. (5) Evans, D. A.; Nelson, J. V.; Vogel, E.; Taber, T. R. J. Am. Chem. Soc. 1981, 103, 3099-3111. The regiochemistry (CH3 vs CH2) of the enolization process with Bu2BOTf and Chx2BCl with these methyl ketone substrates is high (>95:5). In certain cases, 9-BBNOTf is nonselective in this enolization process. Table 1. 1,5-Induction with Various Metal Enolates
TL;DR: In this article, the steric repulsion of the PR2 groups within the chelating fragment was found to significantly influence the coordination geometry of [(P2)Rh], depending on the nature and length of the backbone (X).
Abstract: The complexes [(P2)Rh(hfacac)] 1 [P2 = R2P-(X)-PR2] are introduced as model compounds for the investigation of the intrinsic steric properties of the [(P2)Rh] fragment. The ligand exchange processes that occur during the syntheses of 1 from [(cod)Rh(hfacac)] and the appropriate chelating diphosphanes 3 were studied by variable-temperature multinuclear NMR spectroscopy. The molecular structures of eight examples of 1 with systematic structural variations in 3 were determined by X-ray crystallography. The steric repulsion of the PR2 groups within the chelating fragment was found to significantly influence the coordination geometry of [(P2)Rh], depending on the nature and length of the backbone (X). A linear correlation between the P-Rh-P angles in the solid state and the 103Rh chemical shifts reveals a similar geometric situation in solution. A unique molecular modeling approach was developed to define the accessible molecular surface (AMS) of the rhodium center within the flexible [(P2)Rh] fragment. The potential of this model for application in homogeneous catalysis was exemplified by the use of 1 as catalysts in a test reaction, the hydrogenation of CO2 to formic acid. Complexes 1 were found to be the most active catalyst precursors for this process in organic solvents known to date.
TL;DR: In this paper, a comparative study was made using IR and Raman spectroscopy of theoretical calculations of the vibrational spectra of a series of carbohydrates differing in the configuration of CO (CH) bonds in various positions of the pyranose ring.
TL;DR: In this article, the effect of various substituents at the aromatic ring is examined and the ruthenium-catalyzed reaction of carbon-hydrogen bonds in aromatic ketones with olefins is obtained.
Abstract: To obtain further insight into the new ruthenium-catalyzed reaction of carbon–hydrogen bonds in aromatic ketones with olefins, the effect of various substituents at the aromatic ring is examined. Reaction of o-methylacetophenone with triethoxyvinylsilane (2) in the presence of [Ru(H)2(CO)(PPh3)3] (3)as the catalyst gave the 1 : 1 addition product in quantitative yield. Similarly, the ketone having an o-CF3 group gave the coupling product 9 in 92% yield. However, ortho substituents such as OMe, F, and CN, seem to react with and kill the catalyst so that no efficient reaction was attained. In the cases of the reactions of p-methoxy- and p-fluoroacetophenones with 2, the corresponding 1 : 2 addition products were obtained as the major products. In the cases of m-substituted acetophenones, two different C–H bonds at the ortho positions are available. The C–C bond formation preferentially occurred at the sterically less congested positions. Exceptions are the reactions of m-methoxy- and m-fluoroacetophenones, ...
TL;DR: The structure, orientation and morphology of self-assembled monolayers of a semifluorinated n-alkanethiol, F(CF2)8(CH2)11SH (F8H11SH), have been investigated by polarized IR, angular dependent XPS, ToF-SIMS, contact angle, and ellipsometric measurements and revealed competitive adsorption occurs in the former, producing monolayer that are deficient in the shorter F8SH molecules.
Abstract: The structure, orientation and morphology of self-assembled monolayers of a semifluorinated n-alkanethiol, F(CF2)8(CH2)11SH (F8H11SH), have been investigated by polarized IR, angular dependent XPS, ToF-SIMS, contact angle, and ellipsometric measurements. The orientation of the all trans hydrocarbon segment was found to be tilted much less from the surface normal than the 30° tilt found for octadecanethiol. This has been attributed to the steric constraints imposed by the larger cross section fluorocarbon helices that subsequently are tilted from the surface normal. In addition, studies of dual component mixtures of F8H11SH/F8SH and F8SH/F8H2SH have revealed that competitive adsorption occurs in the former, producing monolayers that are deficient in the shorter F8SH molecules, while in the latter equal representation of both F8SH and F8H2SH molecules are found on the surface due to their similar molecular lengths.
TL;DR: In this paper, the first comprehensive analysis of such equilibria and related binding phenomena with chiral transition metal Lewis acids is presented. But the analysis is limited to the pyramidal rhenium fragment (η5−C5H5)Re(No)(PPh3)+ (I).
Abstract: Prochiral alkenes, aldehydes, and ketones constitute the most frequently used starting materials for enantioselective organic syntheses. Protocols often involve chiral binding agents or Lewis acids that can give two diastereomeric adducts, the ratios of which are measures of chiral recognition. With π adducts, the diastereomers differ in the enantioface of the CC or OC group bound to the Lewis acid. This review provides the first comprehensive analysis of such equilibria and related binding phenomena with chiral transition metal Lewis acids. An extensive body of data from the authors' laboratory for complexes of the pyramidal rhenium fragment [(η5−C5H5)Re(No)(PPh3)]+ (I) affords particular insight. Literature data for other complexes are also summarized. A general model for chiral recognition based upon the relative steric properties of four quadrants is presented. This enables binding selectivities to be individually and rationally optimized for different classes of ligands. Electronic effects are also identified and correlated with specific structural properties. Relationships between binding equilibria, reactivity, and product configurations are discussed.
TL;DR: In this article, the second-order Moller−Plesset perturbational method was used to study base stacking and H-bonding properties of thioguanine and thiouracils.
Abstract: Base stacking and H-bonding properties of thioguanine and thiouracils were studied using an ab initio quantum chemical method with inclusion of electron correlation (second-order Moller−Plesset perturbational method). Hydrogen-bonded base pairs containing thiobases are only slightly less stable (up to 2 kcal/mol) than the unmodified base pairs. The N···S distances are larger by 0.4−0.7 A compared to the N···O distances in the standard base pairs. The thio group enhances polarizability of the monomers and their dipole moments. Thus, in stacked complexes of thiobases, both dispersion attraction and electrostatic interactions are enhanced. Mutual contact of the sulfur atoms and their interaction with second-row elements lead to steric clashes destabilizing the stacking, though, in DNA, such clashes should be eliminated by rather small adjustments of the local DNA conformation. The thio group significantly destabilizes the hydration of the 6-position of thioguanine with respect to guanine. The first hydration...
TL;DR: A 2:1 drug:DNA complex that presents Im at both ends of a GC base pair should help unscramble the issue of imidazole reading specificity, and side-by-side Im and Py rings differentiate GC from CG base pairs.
TL;DR: Nevirapine resistance could arise from a combination of loss of stabilizing interactions and emergence of steric and thermodynamic barriers for drug binding, depending on the particular amino acid substitution involved.
TL;DR: In this paper, the electronic and steric effects of electropositive silyl groups play an important role in making disilynes (RSi⋮SiR) an interesting synthetic target.
TL;DR: In this article, a series of manganese perovskites was used to measure electrical resistivity up to 11 kbar and it was found that the Curie temperature was itself a function of the electronic bandwidth.
Abstract: Quasi-hydrostatic-pressure measurements of electrical resistivity up to 11 kbar are presented for a series of manganese perovskites ${L}_{2/3}{A}_{1/3}{\mathrm{MnO}}_{3}$ It is found that the Curie temperature ${T}_{C},$ being itself a function of the electronic bandwidth $W,$ displays a larger variation of $d\mathrm{ln}{T}_{C}/dP$ as the bandwidth is reduced It is shown that this effect arises primarily from the Mn-O-Mn bond stretching under pressure However, the observed $d\mathrm{ln}{T}_{C}/dP$ versus ${T}_{C}$ or $W$ variations are found to be significantly larger than expected on the basis of simple steric modifications of bandwidth We suggest that the electron-phonon coupling is substantially reduced under pressure; this effect is more prominent as the bandwidth is reduced
TL;DR: Sterically hindered aluminium aryloxides have been developed as designer Lewis acid catalysts for stereo-, regio-and chemo-selective reactions as discussed by the authors, and these aluminium reagents coordinate strongly with various======oxygen-containing substrates, and this coordination is affected by the======consuming environment of their ligands.
TL;DR: In this paper, the steric interactions between the R2 group and the equatorial chloride atom, leading to out-of-plane bending of the chloride atom were studied. And the angle between the NNN plane and the RhCl axis is 5.34° for 7, 11.73° for 8, and 10.04° for 12.
TL;DR: In this article, the steric factor was dominant in the fluorescence quenching process of AAQ induced by alcohols and hydroperoxides, while the electronic factor was evident among the mole.
Abstract: The molecular mechanism of radiationless deactivation from the excited singlet state of aminoanthraquinones (AAQ) induced by alcohols and hydroperoxides was investigated by time-resolved picosecond fluorescence measurements. AAQ suffered substantial fluorescence quenching with red shifts of their λmax in benzene solution upon addition of alcohol and hydroperoxide. Primary alcohols exhibited the largest quenching effects among 26 alcohols examined, while tertiary alcohols were least effective. The Stern−Volmer constants were well correlated with the 13C NMR chemical shift of the carbinol carbon atom and the contact molecular surface area of the hydroxyl hydrogen of the quenchers, while it apparently did not depend upon pKa values. Contact molecular surface area was revealed to be a good quantitative parameter for the steric effect in the intermolecular hydrogen-bonding interaction. The steric factor was dominant in the fluorescence-quenching process, but the electronic factor becomes evident among the mole...
TL;DR: In this article, the product distribution from nucleophilic attack on (η3-allyl)palladium complexes is analyzed by a combination of molecular mechanics and QSAR techniques.
TL;DR: In this paper, the binding of tetradentate ligands with two N and two O donor sites to copper(II) ion was investigated and it was shown that ligand geometry, steric bulk and electron donating effects of the ligand substituents are among the factors influencing the redox potentials of the complexes.
TL;DR: In this article, the gelation of the biopolymer chitosan in solution through crosslinking reactions with Pt( II ) has been investigated by simultaneously monitoring both the viscosity of the system and the number of metal-amine bonds formed per chitosa chain, as probed spectroscopically.
TL;DR: In this article, the formation of helical isomers is shown to depend on the intramolecular interactions between the constituent helicands of the double helicate; 4'-methyl substituents undergo steric interactions with the 4-substituent of the partner helicand, leading to a modest selectivity.
Abstract: Derivatives of 2,2':6',2'':2'',6'''-quaterpyridine have been prepared which are asymmetrically substituted with alkyl groups in the 4- or 6-position and with various substituents in the 4 '-position. These ligands form dicopper- (I) double helicates which have been investigated by 1 H and 13 C NMR spectroscopic techniques. The formation of helical isomers is shown to depend on the intramolecular interactions between the constituent helicands of the double helicate; 4'-methyl substituents undergo steric interactions with the 4-substituent of the partner helicand, leading to a modest selectivity, although bulky 4-substituents decrease selectivity. In the absence of 4 '-substituents, the smaller pitch permits steric interactions between like 4-substituents of the component helicands. In each case, formation of the head-to-head helicate isomer is preferred.
TL;DR: A series of model peptides containing α‐trifluoromethyl‐substituted amino acids in five different positions relative to the predominant cleavage site of the serine protease α‐chymotrypsin was synthesized by solution methods to investigate the influence of α‐Tfm substitution on the proteolytic stability of peptides.
Abstract: A series of model peptides containing alpha-trifluoromethyl-substituted amino acids in five different positions relative to the predominant cleavage site of the serine protease alpha-chymotrypsin was synthesized by solution methods to investigate the influence of alpha-Tfm substitution on the proteolytic stability of peptides. Proteolysis studies demonstrated absolute stability of peptides substituted to the P1 position and still considerable proteolytic stability for peptides substituted at the P2 and P'2 positions compared with the corresponding unsubstituted model peptide. Comparison with peptides containing the fluorine-free disubstituted amino acid alpha-aminoisobutyric acid allowed to separate electronic from steric effects. Furthermore, the absolute configuration of the alpha-Tfm-substituted amino acid was found to exert considerable effects on the proteolytic stability, especially in P'1 substituted peptides. Investigations of this phenomenon using empirical force field calculations revealed that in the (S,R,S)-diasteromer the steric constraints exhibited by the alpha-Tfm group can be outweighed by an advantageous interaction of the flourine atoms with the serine side chain of the enzyme. In contrast, a favourable interaction between substrate and enzyme is impossible for the (S,S,S)-diastereomer.