Cyclic Hydrogen Bond Network Research Articles

IR + VUV double resonance spectroscopy and extended density functional theory studies of ketone solvation by alcohol: 2-butanone·(methanol)n, n = 1-4 clusters.

Infrared plus vacuum ultraviolet (IR + VUV) photoionization vibrational spectroscopy of 2-butanone/methanol clusters [MEK·(MeOH)n, n = 1-4] is performed to explore structures associated with hydrogen bonding of MeOH molecules to the carbonyl functional group of the ketone. IR spectra and X3LYP/6-31++G(d,p) calculations show that multiple isomers of MEK·(MeOH)n are generated in the molecular beam as a result of several hydrogen bonding sites available to the clusters throughout the size range investigated. Isomer interconversion involving solvating MeOH rearrangement should probably occur for n = 1 and 2. The mode energy for a hydrogen bonded OH stretching transition gradually redshifts as the cluster size increases. Calculations suggest that the n = 3 cluster isomers adopt structures in which the MEK molecule is inserted into the cyclic MeOH hydrogen bond network. In larger structures, the cyclic network may be preserved.

Dialkylammonium tert-Butylmethylphosphinites: Stable Intermediates for the Synthesis of P-Stereogenic Ligands.

The preparation of shelf-stable crystalline salts of tert-butylmethylphosphinous acid borane 1 is described. X-ray analysis of diisopropylammonium tert-butylmethylphosphinite borane 6 revealed the presence of a cyclic hydrogen-bond network in the solid state which accounts for an increased melting point and stability. Dialkylammonium phosphinite boranes are convenient precursors of the chiral tert-butylmethylphosphine fragment. Compound 6 can be used directly in SN2@P reactions with various nucleophiles to yield valuable P-stereogenic intermediates and ligands.

IR–UV spectroscopy of jet-cooled 1-indanol: Restriction of the conformational space by hydration

The effect of hydration on a flexible amphiphilic molecule has been studied on the example of 1-hydroxyindan (1-indanol). Studies in jet-cooled conditions by means of resonance-enhanced two-photon ionization and IR–UV double resonance experiments show that the mono-hydrate 1-indanol(H2O) is formed in a dominant isomer, as well as the di-hydrate 1-indanol(H2O)2. 1-Indanol(H2O) favors a cooperative hydrogen bond pattern with –OH⋯O(H)–H⋯π topology, while 1-indanol(H2O)2 forms a cyclic hydrogen bond network with three OH⋯O interactions. The single conformation observed for the hydrates contrasts with the bare molecule which shows two dominant conformations, with the hydroxyl in axial or in equatorial position, respectively. Hydration therefore results in a restriction of the conformational space and conformational locking.

A Spectroscopic and Computational Study of Propofol Dimers and Their Hydrated Clusters

Propofol (2,6-diisopropylphenol, PPF) homodimers and their complexes with one water molecule are analyzed by means of mass-resolved excitation spectroscopy. Using two-color resonance-enhanced multiphoton ionization (REMPI) the S(1) electronic spectra of these systems are obtained, avoiding fragmentation. Due to the large size of these species, the spectra present a large abundance of lines. Using UV/UV hole-burning spectroscopy, two isomers of PPF(2) are found and the existence of at least three isomers for propofol(2)(H(2)O)(1) (PPF(2)W(1)) is demonstrated. Comparison with the structures calculated at the M06-2X/6-311++G(d,p) and M06-2X/6-31+G(d) levels of theory shows that the main driving forces in PPF(2) are several C-H···π interactions accompanied by dipole-dipole interaction between the OH moieties. On the other hand, there is evidence for the formation of cyclic hydrogen-bond structures in the heterotrimers. A comparison of the results obtained herein with those of similar systems from previously published studies follows.

Formation and hydrogen bonding of a novel POSS-trisilanol

The formation of t-butyl substituted polyhedral silsesquioxanes (POSS) starting from the corresponding silanetriol is reported. Several intermediates involved in this complex condensation process could be identified spectroscopically. In addition, the initial condensation intermediate t-Bu(2)Si(2)O(OH)(4), as well as t-Bu(6)Si(6)O(9) and t-Bu(7)Si(7)O(9)(OH)(3), could be characterized by X-ray crystallography. Owing to the high crystal quality it was possible to experimentally determine the geometric parameters of the unusual cyclic hydrogen bond network in a dimeric POSS trisilanol for the first time. Furthermore, we investigated the structural changes concomitant with dimer formation/dissociation of the t-butyl substituted POSS trisilanol and its methyl analogue.

Theoretical and Experimental Studies of Water Complexes of p- and o-Aminobenzoic Acid

We report studies of supersonically cooled water complexes of p- and o-aminobenzoic acid with one or two water molecules using two-color resonantly enhanced multiphoton ionization (REMPI) spectroscopy. Density functional theory calculations are carried out to identify structural minima of water complexes in the ground state. According to the calculation, water molecules are bound to both the C=O and -OH groups to form a cyclic hydrogen-bond network in the most stable isomer. Vibrational frequency calculations for the first electronically excited state of the most stable isomer agree well with the experimental observation. On the basis of this agreement, we believe that only one isomer exists in our molecular beam. The frequency shifts of a few normal modes caused by the water molecules further confirm the site of water addition. A surprising observation is that, for OABA(H2O)n complexes, abundant intermolecular vibrational modes are clearly observable in the REMPI spectra, while for PABA(H2O)n complexes, these modes are conspicuously missing. A red shift in the transition energy is observed for OABA(H2O)1, while blue shifts are observed for the rest of the complexes. This difference alludes to the relative stabilities of the water complexes of the two aminobenzoic acids in both the ground and excited electronic states. These observations will be discussed in comparison with those from the meta isomer.

A Theoretical and Experimental Study of Water Complexes of m-Aminobenzoic Acid MABA·(H2O)n (n = 1 and 2)

We report studies of supersonically cooled water complexes of m-aminobenzoic acid MABA.(H(2)O)n (n = 1 and 2) using two-color resonantly enhanced multiphoton ionization (REMPI) and UV-UV hole-burning spectroscopy. Density functional theory calculations are also carried out to identify structural minima of water complexes in the ground state. For the most stable isomers of both complexes, water molecules bind to the pocket of the carboxyl group in a cyclic hydrogen bond network. Vibrational frequency calculations for the first electronically excited state (S(1)) of these isomers agree well with the experimental observation. The addition of water molecules has a major impact on the normal mode that involves local motion of the carboxyl group, while negligible effects are observed for other normal modes. On the basis of the hole-burning experiment, two major isomers for each complex are identified, corresponding to the two conformers of the bare compound. Compared with the other two isomers of aminobenzoic acid, the red shifts of the origin bands due to water complexation in MABA are considerably larger. Similar to p-aminobenzoic acid and different from o-aminobenzoic acid, the existence of the intermolecular stretching mode is ambiguous in the REMPI spectrum of MABA.(H(2)O)n.

Structure of Hydrogen-Bonded Clusters of 7-Azaindole Studied by IR Dip Spectroscopy and ab Initio Molecular Orbital Calculation

The IR spectrum of 7-azaindole monomer, 7-azaindole reactive and nonreactive dimers, and (7-azaindole)(H2O)n (n = 1−3) clusters in a supersonic jet from 2600 to 3800 cm-1 have been measured using IR dip spectroscopy. The vibrational transitions in the ground state were clearly observed and were assigned to the CH and NH stretching vibrations of 7-azaindole and the OH stretching vibrations of water molecules in the clusters. The observed IR spectra of 7-azaindole monomer and (7-azaindole)(H2O)n (n = 1−3) clusters were compared to theoretical ones obtained by ab initio MO calculations. From a comparison, it is concluded that (7-azaindole)(H2O)n (n = 1−3) clusters have a ring structure due to a cyclic hydrogen-bond network. This conclusion is consistent with an analysis based on high-resolution spectroscopy. Similarly, the IR dip spectrum suggests that the 7-azaindole reactive dimer has a cyclic hydrogen-bond network, forming a symmetric planar structure. It is strongly suggested from the IR spectrum and the...

A robust structural motif in inclusion crystals of norbile acids

Four norbile acids (norcholic, nordeoxycholic, norchenodeoxycholic and norlithocholic acids) include various organic compounds and have a common robust motif in their crystal structures based on a cyclic hydrogen bond network and steric complementarity in the lipophilic parts.

Structure of 1-Naphthol−Water Clusters Studied by IR Dip Spectroscopy and Ab Initio Molecular Orbital Calculations

The IR spectrum of cis-1-naphthol, trans-1-naphthol, and 1-naphthol·(H2O)n (n = 1−3) clusters has been measured by the IR dip spectroscopy in a supersonic jet. The spectra show clear vibrational structures of the monomers and the clusters in the energy region from 3000 to 3800 cm-1. Observed vibrational transitions are assigned to the OH stretching vibrations of 1-naphthol and waters in the clusters. The size dependence of the IR bands and the cluster geometries are analyzed by using the ab initio MO method at the MP2/6-31G level. From the comparison between the observed and calculated IR spectra, we have concluded that the 1-naphthol acts as the proton donor and a cyclic hydrogen-bond network is formed in the n = 2 and 3 clusters.

Asparagine 229 Mutants of Thymidylate Synthase Catalyze the Methylation of 3-Methyl-2‘-deoxyuridine 5‘-Monophosphate

The conserved Asn 229 of thymidylate synthase (TS) forms a cyclic hydrogen bond network with the 3-NH and 4-O of the nucleotide substrate 2'-deoxyuridine 5'-monophosphate (dUMP). Asn 229 is not essential for substrate binding or catalysis [Liu, l., & Santi, D. B. (1993) Proc. Natl. Acad. Sci. U.S.A. 90, 8604-8608] but is a major determinant in substrate specificity [Liu, l., & Santi, D. V. (1993) Biochemistry 32, 9263-9267]. 3-Methyl-dUMP (3-MedUMP) is neither a substrate nor an inhibitor of wild type TS but is converted to 3-methyl 2'-deoxythymidine 5'-monophosphate by many TS Asn 229 mutants. Some of the Asn 229 mutants (N229C, -I, -M, -A, and -V) have kcat values for 3-MedUMP methylation which are up to about 20% of that for wild type TS-catalyzed methylation of dUMP, and some mutants (N229C and -A) catalyze methylation of 3-MedUMP more efficiently than that of dUMP. Mutants with hydrophobic side chains tended to be more active in catalysis of methylation of 3-MedUMP than those with hydrophilic side chains. The ability of 3-MedUMP to serve as a substrate for Asn 229 mutants shows that the active form of dUMP involves the neutral pyrimidine base and that ionization of the 3-NH group does not occur in the course of catalysis. In contrast to the negligible binding of 3-MedUMP to wild type TS, both 3-MedUMP and dUMP showed similar Km values with the Asn 229 mutants, suggesting similar binding affinities to the mutants. The X-ray crystal structure of the TS N229C--3-MedUMP complex showed that the side chain of Cys 229 was rotated away from the pyrimidine ring to allow placement of a water molecule and the 3-methyl group of 3-MedUMP in the active site. Our results suggest that the inability of 3-MedUMP to undergo methylation by wild type TS is due to its inability to bind to the enzyme, which in turn is simply a result of steric interference of the 3-methyl group with the side chain of Asn 229.

Exclusion of 2'-deoxycytidine 5'-monophosphate by asparagine 229 of thymidylate synthase.

In thymidylate synthase (TS, EC 2.1.1.45), the only side chain in direct hydrogen bonding with the pyrimidine ring of the substrate dUMP is asparagine 229 (N229). In binary and ternary complexes, the carboxamide moiety of the side chain of N229 forms a cyclic hydrogen bond network bridging N-3 and O-4 of the uracil heterocycle. Most of the N229 mutants of TS bind dUMP and catalyze dTMP formation as well as the wild-type enzyme; thus, N229 does not contribute to binding of dUMP. Wild-type TS binds dCMP weakly and does not accept dCMP as a substrate. Mutations at N229 of TS modify the interaction of TS with dCMP. TS N229D and TS N229E catalyze the methylation of dCMP [Liu, L., & Santi, D. V. (1992) Biochemistry 31, 5010-5014]. With the exception of the TS N229Q, most of the N229 mutants bind dCMP as well as or tighter than dUMP and bind dCMP 300-3000-fold tighter than wild-type TS. We conclude that TS discriminates binding of dUMP versus dCMP by a 3-4 kcal mol-1 difference in binding energy by exclusion of dCMP from the active site. We propose that this exclusion is a consequence of untoward interactions between dCMP and the side-chain carboxamide group of the Asn or Gln at position 229 of TS. We speculate that exclusion of cytosine versus uracil by Asn or Gln may account for specificity observed in other protein-pyrimidine interactions.

Mutation of asparagine 229 to aspartate in thymidylate synthase converts the enzyme to a deoxycytidylate methylase.

The conserved Asn 229 of thymidylate synthase (TS) forms a cyclic hydrogen bond network with the 3-NH and 4-O of the nucleotide substrate dUMP. The Asn 229 to Asp mutant of Lactobacillus casei thymidylate synthase (TS N229D) has been prepared, purified, and investigated. Steady-state kinetic parameters of TS N229D show 3.5- and 10-fold increases in the Km values of CH2H4folate and dUMP, respectively, and a 1000-fold decrease in kcat. Most important, the Asp 229 mutation changes the substrate specificity of TS to an enzyme which recognizes and methylates dCMP in preference to dUMP. With TS N229D the Km for dCMP is bout 3-fold higher than for dUMP, and the Km for CH2H4folate is increased about 5-fold; however, the kcat for dCMP methylation is 120-fold higher than that for dUMP methylation. Specificity for dCMP versus dUMP, as measured by kcat/Km, changes from negligible with wild-type TS to about a 40-fold increase with TS N229D. TS N229D reacts with CH2H4folate and FdUMP or FdCMP to form ternary complexes which are analogous to the TS-FdUMP-CH2H4folate complex. From what is known of the mechanism and structure of TS, the dramatic change in substrate specificity of TS N229D is proposed to involve a hydrogen bond network between Asp 229 and the 3-N and 4-NH2 of the cytosine heterocycle, causing protonation of the 3-N and stabilization of a reactive imino tautomer. A similar mechanism is proposed for related enzymes which catalyze one-carbon transfers to cytosine heterocycles.