Yeast (Saccharomyces cerevisiae) alcohol dehydrogenase I (ADH1) is the constitutive enzyme that reduces acetaldehyde to ethanol during the fermentation of glucose. ADH1 is a homotetramer of subunits with 347 amino acid residues. A structure for ADH1 was determined by X-ray crystallography at 2.4 Å resolution. The asymmetric unit contains four different subunits, arranged as similar dimers named AB and CD. The unit cell contains two different tetramers made up of “back-to-back” dimers, AB:AB and CD:CD. The A and C subunits in each dimer are structurally similar, with a closed conformation, bound coenzyme, and the oxygen of 2,2,2-trifluoroethanol ligated to the catalytic zinc in the classical tetrahedral coordination with Cys-43, Cys-153, and His-66. In contrast, the B and D subunits have an open conformation with no bound coenzyme, and the catalytic zinc has an alternative, inverted coordination with Cys-43, Cys-153, His-66, and the carboxylate of Glu-67. The asymmetry in the dimeric subunits of the tetramer provides two structures that appear to be relevant for the catalytic mechanism. The alternative coordination of the zinc may represent an intermediate in the mechanism of displacement of the zinc-bound water with alcohol or aldehyde substrates. Substitution of Glu-67 with Gln-67 decreases the catalytic efficiency by 100-fold. Previous studies of structural modeling, evolutionary relationships, substrate specificity, chemical modification, and site-directed mutagenesis are interpreted more fully with the three-dimensional structure.

In the title compound, C14H19N4O3+·C5H7O4−, trimethoprim (TMP) is protonated. In the glutarate anion, one of the two carboxyl­ic acid groups is deprotonated while the other exists as —COOH. The carboxyl group of the hydrogen glutarate ion makes a hydrogen‐bonding pattern with N—H groups of the trimethoprim cation which is similar to the carboxyl­ate group (of Asp‐27 of DHFR)‐trimethoprim cation interaction observed in trimethoprim–DHFR complexes. Two TMP cations and two hydrogen glutarate anions are arranged about an inversion center so that complementary DDAA arrays of quadruple hydrogen‐bonding patterns are formed. The hydrogen glutarate ion bridges the 2‐amino and 4‐amino groups of TMP. There are also carboxyl–carboxyl­ate hydrogen‐bonding interactions involving a head‐to‐tail arrangement of hydrogen glutarate ions which leads to hydrogen‐bonded supramolecular ribbons.

The present study deals with the crystal structures of four organic salts, namely, trimethoprim benzene sulfonate monohydrate 1, trimethoprim sulfanilate monohydrate 2, trimethoprim p-toluene sulfonate 3 and trimethoprim 3-carboxy-4-hydroxybenzene sulfonate dihydrate 4. Trimethoprim (TMP) is protonated at one of the ring nitrogens of the pyrimidine ring. Generally, in the TMP carboxylate complexes, the protonated pyrimidine ring is hydrogen-bonded to the carboxylate group forming a cyclic fork-like hydrogen-bonded bimolecular motif. In structures 1-3, the sulfonate group plays the role of the carboxylate anion. In compounds 1 and 2, there is no pairing of the pyrimidine rings because the pairing sites are blocked by water molecules donating hydrogen to the unprotonated ring nitrogen. Two of the cyclic motifs are bridged by the water molecule donating two hydrogen atoms, leading to a hydrogen-bonded supramolecular chain. This chain pairs with another chain running in the opposite direction. These two chains are cross-linked by O-H … O hydrogen bonds. In compound 2, two of the hydrogen atoms of the amino group of the sulfanilate bridge two methoxy oxygen of the two TMP cations via N-H … O hydrogen bonds resulting in a supramolecular zig-zag chain. In compound 3, two inversion related cyclic motifs are paired through a pair of N-H … N hydrogen bonds involving the 4-amino group and the N3 atom of the pyrimidine ring. In addition to the pairing, one of the sulfonate oxygen atoms bridges the 2-amino and 4-amino groups on either side of the paired bases, resulting in a self-complementary DADA (D represents the hydrogen bond donor and A represents hydrogen bond acceptor) array of quadruple hydrogen bonding patterns. In compound 4, one of the water molecules forms a hydrogen-bonded dimer with the inversion-related water molecule. The 3-carboxy-4-hydroxybenzene sulfonate moiety self-assembles into a supramolecular chain along the c axis through O-H … O hydrogen bonds. Two such oppositely running supramolecular chains are connected by dimeric and monomeric water molecules. The variation of supramolecular organization via hydrogen bonding in the four different trimethoprim sulfonate salts has been discussed.

In the crystal structures of two organic salts, namely, trimethoprim sorbate dihydrate (1) and trimethoprim o-nitrobenzoate (2), the pyrimidine moieties of trimethoprim are protonated at one of the ring nitrogens. In both the compounds, the carboxylate oxygens are hydrogen-bonded to the protonated pyrimidine rings to form the hydrogen-bonded cyclic bimolecular motif. These motifs further self-organize in two different ways to give different types of hydrogen-bonded networks in the two crystal structures. In compound 1, the two inversion related motifs pair through a pair of N-H‚‚‚N hydrogen bonds involving an unprotonated ring nitrogen and 4-amino group. In addition to this pairing, one of the water oxygens bridges the 2-and 4-amino groups on both sides of pairing to form a complementary DADA (D refers to the hydrogen-bond donor and A refers to the hydrogen-bond acceptor) array of quadruple hydrogen bonds. In compound 2, there is no base-pairing, and the cyclic hydrogen-bonded bimolecular motifs self-assemble into a hydrogen-bonded supramolecular ladder through N-H‚‚‚O and C-H‚‚‚O hydrogen bonds. The o-nitrobenzoate ions form a supramolecular chain, the ions being linked by aromatic C-H‚‚‚O (of the nitro group) hydrogen bonds.

In the crystal structure of the title compound, [CdBr2(C4H5N3O)2], two N atoms at the 3‐position of the cytosine ligands and the two bromide ions complete the distorted tetrahedral geometry around the CdII atom. The cytosine ligands of one type are paired through N—H⋯O hydrogen bonds while the cytosine ligands of another type are chained through N—H⋯O hydrogen bonds.