Showing papers on "Hydrogen bond published in 1993"

Application of RESP charges to calculate conformational energies, hydrogen bond energies, and free energies of solvation

Abstract: We apply a new restrained electrostatic potential fit charge model (two-stage RESP) to conformational analysis and the calculation of intermolecular interactions Specifically, we study conformational energies in butane, methyl ethyl thioether, three simple alcohols, three simple amines, and 1,2-ethanediol as a function of charge model (two-stage RESP us standard ESP) and 1-4 electrostatic scale factor We demonstrate that the two-stage RESP model with a 1-4 electrostatic scale factor of ∼1/12 is a very good model, as evaluated by comparison with high-level ab initio calculations For methanol and N-methylacetamide interactions with TIP3P water, the two-stage RESP model leads to hydrogen bonds only slightly weaker than found with the standard ESP changes

Structure and hydrogen bond dynamics of water–dimethyl sulfoxide mixtures by computer simulations

Abstract: We have used two different force field models to study concentrated dimethyl sulfoxide (DMSO)–water solutions by molecular dynamics. The results of these simulations are shown to compare well with recent neutron diffraction experiments using H/D isotope substitution [A. K. Soper and A. Luzar, J. Chem. Phys. 97, 1320 (1992)]. Even for the highly concentrated 1 DMSO : 2 H2O solution, the water hydrogen–hydrogen radial distribution function,g HH(r), exhibits the characteristic tetrahedral ordering of water–water hydrogen bonds. Structural information is further obtained from various partial atom–atom distribution functions, not accessible experimentally. The behavior of water radial distribution functions,g OO(r) and g OH(r) indicate that the nearest neighbor correlations among remaining water molecules in the mixture increase with increasing DMSO concentration. No preferential association of methyl groups on DMSO is detected. The pattern of hydrogen bonding and the distribution of hydrogen bond lifetimes in the simulated mixtures is further investigated. Molecular dynamics results show that DMSO typically forms two hydrogen bonds with water molecules. Hydrogen bonds between DMSO and water molecules are longer lived than water–water hydrogen bonds. The hydrogen bond lifetimes determined by reactive flux correlation function approach are about 5 and 3 ps for water–DMSO and water–water pairs, respectively, in 1 DMSO : 2 H2O mixture. In contrast, for pure water, the hydrogen bond lifetime is about 1 ps. We discuss these times in light of experimentally determined rotational relaxation times. The relative values of the hydrogen bond lifetimes are consistent with a statistical (i.e., transition state theory) interpretation.

Structure and hydrogen bond dynamics of water-dimethyl sulfoxide mixtures by computer simulations. Interim report, April 1992-October 1993

Abstract: The authors have used two different force field models to study concentrated dimethyl sulfoxide (DMSO)-water solutions by molecular dynamics. The results of these simulations are shown to compare well with recent neutron diffraction experiments using H/D isotope substitution. Even for the highly concentrated 1DMSO : 2H2O solution, the water hydrogen-hydrogen radial distribution function, gHH(r), exhibits the characteristic tetrahedral ordering of water-water hydrogen bonds. Structural information is, further obtained from various partial atom-atom distribution functions, not accessible experimentally. The behavior of water radial distribution functions, goo(r) and goH(r) indicate that the nearest neighbor correlations among remaining water molecules in the mixture increase with increasing DMSO concentration. No preferential association of methyl groups on DMSO is detected. The pattern of hydrogen bonding and the distribution of hydrogen bond lifetimes in the simulated mixtures is further investigated. Molecular dynamics results show that DMSO typically forms two hydrogen bonds with water molecules. Hydrogen bonds between DMSO and water molecules are longer lived than water-water hydrogen bonds. The hydrogen bond lifetimes determined by reactive flux correlation function approach are about 5 ps and 3 ps for water-DMSO and water-water pairs, respectively, in 1DMSO: 2H20 Mixture. In contrast, for pure water, the hydrogen bond lifetime ismore » about 1 ps. They discuss these times in light of experimentally determined rotational relaxation times. The relative values of the hydrogen bond lifetimes are consistent with a statistical (i.e., transition state theory) interpretation.« less

Crystal structure of Escherichia coli TEM1 beta-lactamase at 1.8 A resolution.

Abstract: The X-ray structure of Escherichia coli TEM1 beta-lactamase has been refined to a crystallographic R-factor of 16.4% for 22,510 reflections between 5.0 and 1.8 A resolution; 199 water molecules and 1 sulphate ion were included in refinement. Except for the tips of a few solvent-exposed side chains, all protein atoms have clear electron density and refined to an average atomic temperature factor of 11 A2. The estimated coordinates error is 0.17 A. The substrate binding site is located at the interface of the two domains of the protein and contains 4 water molecules and the sulphate anion. One of these solvent molecules is found at hydrogen bond distance from S70 and E166. S70 and S130 are hydrogen bonded to K73 and K234, respectively. It was found that the E. coli TEM1 and Staphylococcus aureus PC1 beta-lactamases crystal structures differ in the relative orientations of the two domains composing the enzymes, which result in a narrowed substrate binding cavity in the TEM1 enzyme. Local but significant differences in the vicinity of this site may explain the occurrence of TEM1 natural mutants with extended substrate specificities.

Role of C-H.cntdot..cntdot..cntdot.O hydrogen bonds in the coordination of water molecules. Analysis of neutron diffraction data

Abstract: C-H...O hydrogen bonds with water acceptors are analyzed from 101 water molecules in 46 neutron crystal structures. The shortest observed hydrogen bond distances are H...O W ∼2.3A and C...O W ∼3.1 A. About 8% of the water molecules accept C-H...O W interactions with H...O W separations<2.5 A AND 39% WITH H...O W <2.8 A. CH donors may coordinate to water molecules in concert with OH and NH donors and with metal ions in many different combinations. The most frequent function of C-H...O W hydrogen bonds is to complete a tetrahedral coordination geometry around the water

The energetics of ion-pair and hydrogen-bonding interactions in a helical peptide.

Abstract: A single pair of Glu and Lys residues has been placed at four different spacings, and in both orientations, in an otherwise neutral alanineglutamine peptide helix, and the contribution to helix stability of the different Glu-Lys interactions has been measured. The contribution from the interaction of each charged side chain with the helix macrodipole has also been determined. A side-chain interaction between Gln and Glu, when the spacing is (i, i+4), has been detected and quantified. The interactions have been divided into contributions from hydrogen bonds (independent of the concentration of NaC1) and from electrostatic interactions (present in 10 mM NaCl, absent in 2.5 M NaCl). The major results are as follows: (1) The (i, i+3) and (i, i+4) Glu-Lys interactions are helix-stabilizing and are similar in strength to each other, regardless of the orientation of the side chains. (2) Hydrogen bonds provide the major contribution to these side-chain interactions, as shown by the following facts. First, the major part of the interaction observed in 10 mM NaCl, pH 7, is still present in 2.5 M NaCl. Second, the interaction found at pH 2 is equally as strong as that found in 2.5 M NaCl at pH 7. (3) The (i, i+4) Gln-Glu side-chain hydrogen bond is as strong as the hydrogen-bond component of the Glu-Lys interaction at both pH 2 and pH 7. The Gln-Glu interaction differs from the Glu-Lys interaction in being specific both for the orientation and the spacing of the residues. (4) No significant hydrogen-bonding interaction was found for the (i, i+1) or (i, i+2) Glu-Lys spacings, either at pH 2 or at pH 7, in 2.5 M NaCl. At 10 mM NaCl and pH 7, these spacings show a helix-destabilizing electrostatic interaction which probably results from stabilization of the coil conformation.

The Asp-His-Fe triad of cytochrome c peroxidase controls the reduction potential, electronic structure, and coupling of the tryptophan free radical to the heme.

Abstract: The buried charge of Asp-235 in cytochrome c peroxidase (CCP) forms an important hydrogen bond to the histidine ligand of the heme iron. The Asp-His-metal interaction, which is similar to the catalytic triad of serine proteases, is found at the active site of many metalloenzymes and is believed to modulate the character of histidine as a metal ligand. We have examined the influence of this interaction in CCP on the function, redox properties, and iron zero-field splitting in the native ferric state and its effect on the Trp-191 free radical site in the oxidized ES complex. Unlike D235A and D235N, the mutation D235E introduces very little perturbation in the X-ray crystal structure of the enzyme active site, with only minor changes in the geometry of the carboxylate-histidine interaction and no observable change at the Trp-191 free radical site. More significant effects are observed in the position of the helix containing residue Glu-235. However, the small change in hydrogen bond geometry is all that is necessary to (1) increase the reduction potential by 70 mV, (2) alter the anisotropy of the Trp-191 free radical EPR, (3) affect the activity and spin-state equilibrium, and (4) reduce the strength of the iron ligand field as measured by the zero-field splitting. The changes in the redox potential with substitution are correlated with the observed zero-field splitting, suggesting that redox control is exerted through the heme ligand by a combination of electrostatic and ligand field effects. The replacement of Asp-235 with Glu appears to result in a significantly weaker hydrogen bond in which the proton resides essentially with His-175. This hydrogen bond is nevertheless strong enough to prevent the reorientation of Trp-191 and the conversion to one of two low-spin states observed for D235A and D235N. The Asp-His-Fe interaction is therefore as important in defining the redox properties and imidazolate character of His-175 as has been proposed, yet its most important role in peroxidase function may be to correctly orient Trp-191 for efficient coupling of the free radical to the heme and to maintain a high-spin 5-coordinate heme center.

Hydrogen bonding in the benzene–ammonia dimer

Abstract: AMINES have long been characterized as amphoteric (acting as both donor and acceptor) in terms of their hydrogen-bond interactions in the condensed phase. With the possible exception of (NH_3)_2, however, no gas-phase complexes exhibiting hydrogen-bond donation by ammonia, the ‘simplest amine’, have been observed. Here we present high-resolution optical and microwave spectra of the benzene–ammonia dimer in the gas phase, which show that the ammonia molecule resides above the benzene plane and undergoes free or nearly free internal rotation. In the vibrationally averaged structure, the C_3 symmetry axis of NH_3 is tilted by about 58° relative to the benzene C_6 axis, such that the ammonia protons interact with the benzene π-cloud. Our ab initio calcula-tions predict a 'monodentate' minimum-energy structure, with very low barriers to rotation of ammonia. The larger separation of the two molecular components, and the smaller dissociation energy, relative to the benzene–water dimer reflect the weak hydrogen-bond donor capability of ammonia, but the observed geometry greatly resembles the amino–aromatic interaction found naturally in proteins.

Facile intermolecular activation of carbon-hydrogen bonds in methane and other hydrocarbons and silicon-hydrogen bonds in silanes with the iridium(III) complex Cp*(PMe3)Ir(CH3)(OTf)

Abstract: The activation of compounds containing aliphatic C-H bonds and the transformations of these materials into functionalized organic compounds are major goals of organometallic and catalytic chemistry. Late transition metals typically react with hydrocarbons by oxidative addition of C-H bonds to low-valent, electron-rich metal centers, such as the reactive Ir(I) species Cp*IrL (Cp* = ([eta][sup 5]-C[sub 5]Me[sub 5]); L = tertiary phosphine). We now report that the more electron-deficient iridium(III) center in the trifluoromethanesulfonate (triflate) complex Cp* (PMe[sub 3])Ir (CH[sub 3]) (OTf) (1, OTf = OSO[sub 2]CF[sub 3]) reacts with several types of aliphatic C-H bonds, including that in methane, as well as with the Si-H bonds in silanes. 26 refs., 1 fig.

The interatomic structure of water at supercritical temperatures

Abstract: LIQUID water, the medium in which life both began and persists, is in many ways a most unusual fluid. Much is known about the macroscopic properties of the condensed and gaseous states of water, but our understanding of the microscopic forces that define water structure remains incomplete1. This structure, described in terms of correlations between the pairs of atoms O–H, O–O and H–H (ref. 2), can be studied by neutron diffraction techniques involving isotopic substitution3. In particular, the signature of hydrogen bonding is apparent in neutron diffraction experiments as a peak in the pair correlation function of O and H (gOH (r)) at about 1.9 A (refs 3, 4). Here we extend such studies into the supercritical regime of water, in which there is no longer any distinction between the liquid and vapour phases. We find that at the supercritical temperature of 400 °C almost all hydrogen bonding is broken down, even though the thermal energy kBT is considerably less than the energy of the hydrogen bond. Our results are markedly different from the predictions of computer simulations under comparable conditions5 using a common model of water5–7. Our results provide a sensitive test of models of water structure more generally, and give some indication of the environment that solute molecules will experience in extraction and reaction processes that employ supercritical water as a solvent8.

Molecular Orientation of Silane at the Surface of Colloidal Silica

Abstract: The objective of this study was to investigate the silica-silane bond formation present at the filler interface of dental composites Diffuse reflectance infrared Fourier transform spectroscopy was used, and the spectra of pyrogenic silica (Cab-O-Sil) treated with different concentrations of gamma-methacryloxypropyltrimethoxysilane (MPS) were analyzed The outcome of the study suggested that the gamma-methacryloxypropyltrimethoxysilane (MPS) molecules oriented parallel to the colloidal silica surface (Cab-O-Sil) and formed two types of bonds One of these bonds was a siloxane bridge formed by a condensation reaction between the silanol groups of both the silica surface and the hydrolyzed silane Water formed during this reaction and soon became recaptured by the silanol groups of the silica surface These water molecules were not available for additional hydrolyzation reactions of the unhydrolyzed silane under the experimental conditions The intensity of the isolated OH-groups decreased because of this reaction Simultaneous with the condensation reaction, the carbonyl group of the MPS molecule formed hydrogen bonds This hydrogen bond formation resulted in a peak shift of the carbonyl band from 1718-1720 cm-1 to 1700-1702 cm-1 This hydrogen bond formation also occurred with the isolated OH-groups After consumption of the isolated OH-groups, no additional surface reaction occurred because no further OH-groups were available for additional condensation reactions or hydrogen bond formation The findings suggest that the amount of silane needed for filler treatment depends on the number of isolated OH-groups available on the filler surface

Further development of hydrogen bond functions for use in determining energetically favorable binding sites on molecules of known structure. 1. Ligand probe groups with the ability to form two hydrogen bonds

Abstract: The directional properties of hydrogen bonds play a major role in determining the specificity of intermolecular interactions. An energy function which takes explicit account of these properties has been developed for use in the determination of energetically favorable ligand binding sites on molecules of known structure by the GRID method (Goodford, P.J.J. Med. Chem. 1985, 28, 849. Boobbyer, D.N.A.; Goodford, P.J.; McWhinnie, P.M.; Wade, R.C.J. Med. Chem. 1989, 32, 1083). In this method, the interaction energy between a target molecule and a small chemical group (a probe), which may be part of a larger ligand, was calculated using an energy function consisting of Lennard-Jones, electrostatic, and hydrogen bond terms. The latter term was a function of the length of the hydrogen bond, its orientation at the hydrogen-bonding atoms, and their chemical nature. We now describe hydrogen bond energy functions which take account of the spatial distribution of the hydrogen bonds made by probes with the ability to form two hydrogen bonds. These functions were designed so as to model the experimentally observed angular dependence of the hydrogen bonds. We also describe the procedure to locate the position and orientation of the probe at which the interaction energy is optimized. The use of this procedure is demonstrated by examples of biological and pharmacological interest which show that it can produce results that are consistent with other theoretical approaches and with experimental observations.

Crystal structures of aconitase with isocitrate and nitroisocitrate bound.

Abstract: The crystal structures of mitochondrial aconitase with isocitrate and nitroisocitrate bound have been solved and refined to R factors of 0.179 and 0.161, respectively, for all observed data in the range 8.0-2.1 A. Porcine heart enzyme was used for determining the structure with isocitrate bound. The presence of isocitrate in the crystals was corroborated by Mossbauer spectroscopy. Bovine heart enzyme was used for determining the structure with the reaction intermediate analogue nitroisocitrate bound. The inhibitor binds to the enzyme in a manner virtually identical to that of isocitrate. Both compounds bind to the unique Fe atom of the [4Fe-4S] cluster via a hydroxyl oxygen and one carboxyl oxygen. A H2O molecule is also bound, making Fe six-coordinate. The unique Fe is pulled away approximately 0.2 A from the corner of the cubane compared to the position it would occupy in a symmetrically ligated [4Fe-4S] cluster. At least 23 residues from all four domains of aconitase contribute to the active site. These residues participate in substrate recognition (Arg447, Arg452, Arg580, Arg644, Gln72, Ser166, Ser643), cluster ligation and interaction (Cys358, Cys421, Cys424, Asn258, Asn446), and hydrogen bonds supporting active site side chains (Ala74, Asp568, Ser571, Thr567). Residues implicated in catalysis are Ser642 and three histidine-carboxylate pairs (Asp100-His101, Asp165-His147, Glu262-His167). The base necessary for proton abstraction from C beta of isocitrate appears to be Ser642; the O gamma atom is proximal to the calculated hydrogen position, while the environment of O gamma suggests stabilization of an alkoxide (an oxyanion hole formed by the amide and side chain of Arg644). The histidine-carboxylate pairs appear to be required for proton transfer reactions involving two oxygens bound to Fe, one derived from solvent (bound H2O) and one derived from substrate hydroxyl. Each oxygen is in contact with a histidine, and both are in contact with the side chain of Asp165, which bridges the two sites on the six-coordinate Fe.

An approach to the design of molecular solids. Strategies for controlling the assembly of molecules into two-dimensional layered structures

Abstract: A design strategy for the synthesis of molecular crystals confining two-dimensional layers is formulated and demonstrated by the synthesis and structure determination of a series of dicarboxylic acid urea derivatives. The design strategy is based upon the selection of complementary hydrogen bond functionalities and an accounting of the specific symmetry operators that must correspond to each intermolecular interaction within the molecular crystal. Each of the molecules studied contained a disubstituted urea functionality that was expected to form a one-dimensional hydrogen-bonded network, an a-network, via urea hydrogen bonds. The molecules also contained terminal carboxylic acid or amide residues that were anticipated to unite the a-networks into two-dimensional β-networks via additional hydrogen bonds

Structure, DNA minor groove binding, and base pair specificity of alkyl- and aryl-linked bis(amidinobenzimidazoles) and bis(amidinoindoles)

Abstract: A series of bis(amidinobenzimidazoles) and bis(amidinoindoles) with varied linking chains connecting the aromatic groups and various modifications to the basic amidino groups have been prepared. The calf thymus (CT) DNA and nucleic acid homopolymer [poly(dA).poly(dT),poly(dA-dT).poly-(dA-dT), and poly(dG-dC).poly(dG-dC)] binding properties of these compounds have been studied by thermal denaturation (delta Tm) and viscosity. The compounds show a greater affinity for poly(dA).poly(dT) and poly(dA-dT).poly(dA-dT) than for poly(dG-dC).poly(dG-dC). Viscometric titrations indicate that the compounds do not bind by intercalation. Molecular modeling studies and the biophysical data suggest that the molecules bind to the minor groove of CT DNA and homopolymers. Analysis of the shape of the molecules is consistent with this mode of nucleic acid binding. Compounds with an even number of methylenes connecting the benzimidazole rings have a higher affinity for DNA than those with an odd number of methylenes. Molecular modeling calculations that determine the radius of curvature of four defined groups in the molecule show that the shape of the molecule, as a function of chain length, affects the strength of nucleic acid binding. Electronic effects from cationic substituents as well as hydrogen bonding from the imidazole nitrogens also contribute to the nucleic acid affinity. The bis(amidinoindoles) show no structurally associated differential in nucleic acid base pair specificity or affinity.

The role of hydrogen bonding in carbohydrates: molecular dynamics simulations of maltose in aqueous solution

Abstract: Molecular dynamics simulations of maltose in two different conformations in vacuum and aqueous (TIP3P) solution have been used to examine the types of hydrogen bonds made by this carbohydrate molecule. Maltose was found to be extensively hydrogen bonded to solvent molecules in aqueous solution, and these hydrogen bonds were found to have potential conformational consequences. The exchange of an intramolecular O2-O3' hydrogen bond found in the crystal structure for hydrogen bonds to solvent was observed to produce significant changes in the solvation of the sugar molecule

Hydrogen-bond acceptor abilities of tetrachlorometalate(II) complexes in ionic liquids

Abstract: The novel salts [emim]2[CoCl4] and [emim]2[NiCl4](emim = 1-ethyl-3-methylimidazolium cation) have been prepared for use as crystallographic models in an extended X-ray absorption fine structure (EXAFS) study in ambient-temperature ionic liquids. The salts have been characterized both spectroscopically and crystallographically. The crystals are isomorphous, and contain two distinct anions with differing interactions within the extended hydrogen-bonded structures. The implications of these results for the structure of ambient-temperature ionic liquids are discussed.

X-ray crystal structures of the oxidized and reduced forms of the rubredoxin from the marine hyperthermophilic archaebacterium Pyrococcus furiosus.

Abstract: The structures of the oxidized and reduced forms of the rubredoxin from the archaebacterium, Pyrococcus furiosus, an organism that grows optimally at 100 degrees C, have been determined by X-ray crystallography to a resolution of 1.8 A. Crystals of this rubredoxin grow in space group P2(1)2(1)2(1) with room temperature cell dimensions a = 34.6 A, b = 35.5 A, and c = 44.4 A. Initial phases were determined by the method of molecular replacement using the oxidized form of the rubredoxin from the mesophilic eubacterium, Clostridium pasteurianum, as a starting model. The oxidized and reduced models of P. furiosus rubredoxin each contain 414 nonhydrogen protein atoms comprising 53 residues. The model of the oxidized form contains 61 solvent H2O oxygen atoms and has been refined with X-PLOR and TNT to a final R = 0.178 with root mean square (rms) deviations from ideality in bond distances and bond angles of 0.014 A and 2.06 degrees, respectively. The model of the reduced form contains 37 solvent H2O oxygen atoms and has been refined to R = 0.193 with rms deviations from ideality in bond lengths of 0.012 A and in bond angles of 1.95 degrees. The overall structure of P. furiosus rubredoxin is similar to the structures of mesophilic rubredoxins, with the exception of a more extensive hydrogen-bonding network in the beta-sheet region and multiple electrostatic interactions (salt bridge, hydrogen bonds) of the Glu 14 side chain with groups on three other residues (the amino-terminal nitrogen of Ala 1; the indole nitrogen of Trp 3; and the amide nitrogen group of Phe 29). The influence of these and other features upon the thermostability of the P. furiosus protein is discussed.

Molecular recognition in micelles: the roles of hydrogen bonding and hydrophobicity in adenine-thymine base-pairing in SDS micelles

Abstract: This paper describes a new class of molecular receptors 2 that bind adenine derivatives 3 in aqueous solution by means of hydrogen bonding (base-pairing). The receptors are supramolecular assemblies of thymine groups embedin micelles, which self-assemble when (thyminylalkyl)ammonium salts 1 [Thy-(CH 2 ) n -N + Me 3 ] are mixed with aqueous sodium dodecyl sulfate (SDS) solutions. NMR titration studies and Job's method indicate that binding occurs 1:1 adenine-thymine stoichiometry in a fashion consistent with base-pairing within the micelles. In the absence of SDS base-stacking occurs in preference to base-pairing

Evidence for O-H.cntdot..cntdot..cntdot.C and N-H.cntdot..cntdot..cntdot.C hydrogen bonding in crystalline alkynes, alkenes, and aromatics

Abstract: Attempts have been made to understand the nature and significance of hydrogen bonds of the type X-H-C (X = 0, N) . These unusual interactions have been discussed recently. Crystallographic studies on 17a-ethynylandrosta- 2,4-dieno[2,3-d]dihydroxazol1-7 8-01 (donazole) provide direct evidence of such an 0-H.0-C interaction. Ab initio computations, IR spectroscopy, and database studies show that these hydrogen bonds, while uncommon, are energetically and structurally significant.

An infrared spectroscopic study of the preferential solvation in water-acetonitrile mixtures

Abstract: Mixtures of water and acetonitrile in the full concentration range have been studied by infrared spectroscopy. OD and CN stretching vibrations of HDO and CD 3 CN molecules have been used as probes of the structural environments. Acetonitrile molecules which are unaffected by water molecules are found for a broad concentration range (0.1≤xH 2 O≤0.8), showing that a preferential solvation occurs. The strong tendency for self-association of water molecules is evident from the occurrence of a broad OD stretching band. Chains of water molecules linked by hydrogen bonds are suggested to be formed rather than spherical clusters

Ability of the PM3 quantum-mechanical method to model inter molecular hydrogen bonding between neutral molecules

Abstract: The PM3 semiempirical quantum-mechanical method was found to systematically describe intermolecular hydrogen bonding in small polar molecules. PM3 shows charge transfer from the donor to acceptor molecules on the order of 0.02–0.06 units of charge when strong hydrogen bonds are formed. The PM3 method is predictive; calculated hydrogen bond energies with an absolute magnitude greater than 2 kcal mol−1 suggest that the global minimum is a hydrogen bonded complex; absolute energies less than 2 kcal mol−1 imply that other van der Waals complexes are more stable. The geometries of the PM3 hydrogen bonded complexes agree with high-resolution spectroscopic observations, gas electron diffraction data, and high-level ab initio calculations. The main limitations in the PM3 method are the underestimation of hydrogen bond lengths by 0.1–0.2 A for some systems and the underestimation of reliable experimental hydrogen bond energies by approximately 1–2 kcal mol−1. The PM3 method predicts that ammonia is a good hydrogen bond acceptor and a poor hydrogen donor when interacting with neutral molecules. Electronegativity differences between F, N, and O predict that donor strength follows the order F > O > N and acceptor strength follows the order N > O > F. In the calculations presented in this article, the PM3 method mirrors these electronegativity differences, predicting the F-H---N bond to be the strongest and the N-H---F bond the weakest. It appears that the PM3 Hamiltonian is able to model hydrogen bonding because of the reduction of two-center repulsive forces brought about by the parameterization of the Gaussian core–core interactions. The ability of the PM3 method to model intermolecular hydrogen bonding means reasonably accurate quantum-mechanical calculations can be applied to small biologic systems. © 1993 John Wiley & Sons, Inc.