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Protein-protein complexes play an important role in the physiology and the pathology of cellular functions, and therefore are attractive therapeutic targets. A small subset of residues known as “hot spots”, accounts for most of the protein-protein binding free energy. Computational methods play a critical role in identifying the hotspots on the proteinprotein interface. In this paper, we use a computational alanine scanning method with all-atom force fields for predicting hotspots for 313 mutations in 16 protein complexes of known structures. We studied the effect of force fields, solvation models, and conformational sampling on the hotspot predictions. We compared the calculated change in the protein-protein interaction energies upon mutation of the residues in and near the protein-protein interface, to the experimental change in free energies. The AMBER force field (FF) predicted 86% of the hotspots among the three commonly used FF for proteins, namely, AMBER FF, Charmm27 FF, and OPLS-2005 FF. However, AMBER FF also showed a high rate of false positives, while the Charmm27 FF yielded 74% correct predictions of the hotspot residues with low false positives. Van der Waals and hydrogen bonding energy show the largest energy contribution with a high rate of prediction accuracy, while the desolvation energy was found to contribute little to improve the hot spot prediction. Using a conformational ensemble including limited backbone movement instead of one static structure leads to better predicttion of hotpsots.

In this paper, both 1,4-dihydropyridinones (Hantzsch products) and 3,4-dihydropyrimidinones (Biginelli products) are synthesized in one-pot of aldehydes, β-dicarbonyl compounds and urea, catalyzing by non-toxic room temperature ionic liquid 1-n-butyl-3-methylimidazolium saccharinate (BMImSac). The ionic liquid (BMImSac) is environmentally benign associated with ionic liquid with F−. In order to improve the yield and selectivity, the effects of the mole proportion of reactants and solvents are investigated. Interestingly, by increasing the amount of ethyl acetoacetate or utilizing water as solvent, an unexpected by-product, Hantzsch product which is distinct from Biginelli product, is generated. All Biginelli and Hantzsch products are simultaneously purified and characterized by IR, 1H NMR and 13C NMR, of which one Biginelli product (4h) and one Hantzsch product (5b) are structurally determinated by X-ray single crystal diffraction. The crystal data for 4h: triclinic system, P-1 space group, a = 7.515(3) A, b = 9.011(4) A, c = 11.218(5) A, α = 106.288(6)°, β = 104.644(6)°, γ = 100.234(6)°, Z = 2, V = 679.7(5) A3, Dc = 1.36 g/cm3, R1 = 0.0603. The crystal data for 5b: monoclinic system, P2(1)/c space group, a = 9.765(3) A, b = 7.391(2) A, c = 24.795(7) A, β = 93.669(5)°, Z = 4, V = 1785.7(9) A3, Dc = 1.292 g/cm3, R1 = 0.0440.

Novel 1-phenyl-piperazine-2,6-diones were prepared by a new facile synthetic route using methyl N-substituted iminomonoacetate as starting material. The structures of these compounds were established by (1)H-NMR, (13)C-NMR and GC/MS. 2-(4-Chloro-5-cyclo-pentyl-oxy-2-fluorophenyl)-tetrahydro-2H-pyrido-[1,2-a]-pyrazine-1,3-(4H,6H)-dione displayed the greatest herbicidal activity.

In the search for better herbicides a series of 1-alkyl-3-(α-hydroxy-(un)substituted benzylidene)pyrrolidine-2,4-diones were prepared and their structure-activity relationships studied. All their structures have been confirmed by 1 H-NMR and elemental analysis. The preliminary bioassay results indicated that some of them have high herbicidal activity against annual dicotyledonous and monocotyledonous plants. Keywords: Pyrrolidine, herbicides, inhibition. Introduction The inhibitors of 4-hydroxyphenylpyruvate dioxygenase (HPPD, EC 1.13.11.27) constitute a new kind of herbicides [1]. Generally, potent herbicides of this kind must possess the following structural features: 1) a tricarbonyl methane structure and one of the three carbonyl groups must be a subustituted benzoyl group; 2) the compound must be able to enolise so that the enolate is capable of inhibiting HPPD enzyme by competitive combination with Fe 2+ – the reaction center of HPPD enzyme [2]. Recently, we observed that the 3-acyltetramic acids form an expanding group of antibiotics and pigments derived from microorganisms [3]. They display a range of biological activities [4] and all compounds of this kind possess a tricarbonyl methane structure and can essentially enolise completely (the chemical shifts of their enolic hydroxyls were larger than 10). Tests of their antimicrobial activities indicated that the structure of the acyl substituent at the 3-position and possession of a 3

The structures of methyl 5-[2-chloro-4-(trifluoromethyl)phenoxy]-2-nitrobenzoate, C15H9ClF3N3O5, (I), methyl 2-chloro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]benzoate, C14H10ClF3N2O4, (II), and 2-[4-chloro-2-fluoro-5-(prop-2-ynyloxy)phenyl]-4-(trifluoromethyl)piperidine-2,6-dione, C15H10ClF4NO3, (III), are similar in their dihedral angles and in the distances between the farthest two atoms. There are two independent molecules in the structure of (I). The dihedral angles between the two aromatic rings in each molecule in (I), between the benzene and tetrahydropyrimidine rings in (II), and between the benzene ring and the five-atom planar portion of the piperidine-2,6-dione ring in (III) are 80.78 (11)/89.75 (11), 89.13 (9) and 87.52 (13) degrees , respectively. The distances between the farthest two atoms, viz. O...F in the two molecules of (I), and Cl...F in (II) and (III), are 11.763 (7)/11.953 (6), 10.734 (10) and 10.889 (9) A, respectively. In all three crystal structures, the molecules are linked to generate sheets of molecules via C-H...O interactions.

The molecular structures of 2-[4-chloro-2-fluoro-5-(prop-2-ynyloxy)phenyl]-1,3,4,5,6,7-hexahydroisoindole-1,3-dione, C17H13ClFNO3, (I), and the isomeric compound 2-[4-chloro-2-fluoro-5-(prop-2-ynyloxy)phenyl]-cis-1,3,3a,4,7,7a-hexahydroisoindole-1,3-dione, (II), are, as anticipated, significantly different in their conformations and in the distances between the farthest two atoms. The six-membered ring of the 1,3,4,5,6,7-hexahydroisoindole-1,3-dione moiety in (I) adopts a half-chair conformation. The dihedral angle between the five-membered dione ring of (I) and the benzene ring is 50.96 (7) degrees . The six-membered ring of the cis-1,3,3a,4,7,7a-hexahydroisoindole-1,3-dione moiety in (II) adopts a boat conformation. The dihedral angle in (II) between the five-membered dione ring and the benzene ring is 61.03 (13) degrees . In the crystal structures, the molecules are linked by C-H...O hydrogen bonds and weak pi-pi interactions. Compound (I) is a much more potent herbicide than (II). The Cl...H distances between the farthest two atoms in (I) and (II) are 11.37 and 9.97 A, respectively.

The retention characteristics of 25 2-cyano-3-methylthio-3substituted amine-acrylates are determined using reversed-phase thin-layer chromatography (RP-TLC) with methanol‐water mixtures as eluents. The relationship between R m values and partition coefficients (C log P ) are established. The R m values decrease linearly with increasing methanol concentration in the eluent. The R m values extrapolated to zero organic modifier concentration (R m0 ) in the eluent are highly related to C log P. The R m0 value can be used to evaluate the lipophilicity of this kind of compound.

The crystal structure of the title compound, C18H20N6O3, is stabilized by N—H...O and N—H...N hydrogen bonds.

The title molecule, C17H25N5O3S2, belongs to the family of bis-heterocycles. In the crystal structure, there are one intra- and two intermolecular hydrogen bonds. One of the two pyrazole rings and the six-membered ring formed by the intramolecular hydrogen bond are approximately coplanar.

In the crystal structure of the title compound, C20H20N2O4, the mol­ecules are linked by a weak inter­molecular C—H⋯N hydrogen bond. The molecule has crystallographic twofold rotation symmetry.

The title compound, C16H15F3N2O3, is composed of a 3-(tri­fluoro­methyl)­phenyl ring and a pyridazinone ring, which are approximately coplanar, and an ethyl acetate group on the pyridazinone ring. In the crystal structure, centrosymmetric­ally related mol­ecules form dimers through non-classical intermolecular C—H⋯O hydrogen bonds.

The tetra­hydro­pyrimidine ring of the title mol­ecule, C12H14N2OS, adopts a half-chair conformation. In the crystal structure, the mol­ecules are linked to form centrosymmetric­ally related hydrogen-bonded dimers.

The tetra­hydro­pyrimidine ring of the title mol­ecule, C11H11ClN2OS, adopts a half-chair conformation. In the crystal structure, the mol­ecules are linked to form centrosymmetric hydrogen-bonded dimers.

The title compound, C15H17NO4, is a potent new herbicide containing the pyrrolidine-2,4-dione ring system. In the crystalline state, the molecular skeleton contains one enol grouping, which is intramolecularly hydrogen bonded to a neighboring keto O atom.

The title compound, C18H15NO3, is a potent new herbicide containing the pyrrolidine-2,4-dione ring system. In the crystalline state, the molecular skeleton contains one enol hydrogen-bonded moiety, formed from benzoyl Czdbnd;O isomerization.

In the title compound, C(22)H(19)F(3)N(2)O(3), the benzene rings of the trifluoro-methyl-phenyl and benzoyl-phenyl groups form dihedral angles of 41.89 (10) and 67.44 (10)°, respectively, with the pyridazine ring. The methyl-propanoate group is nearly coplanar with the attached benzene ring [dihedral angle = 3.9 (2)°]. The trifluoro-methyl group is disordered over two positions; the site-occupancy factors are ca 0.64 and 0.36. In the crystal structure, inversion-related mol-ecules are linked through C-H⋯O hydrogen bonds and C-H⋯π inter-actions.

The molecular structures of ethyl 5-amino-3-(4,6-dimethylpyrimidin-2-ylamino)-1-methyl-1H-pyrazole-4-carboxylate, C13H18N6O2, (I), and ethyl 5-amino-3-(4,6-dimethylpyrimidin-2-ylamino)-1-(2-nitrophenylsulfonyl)-1H-pyrazole-4-carboxylate, C18H19N7O6S, (II), have been determined. There are two intramolecular N-H...O bonds and one intermolecular N-H...O hydrogen bond in (I). The rings formed by the N-H...O hydrogen bonds are almost planar. In (II), three intramolecular N-H...O hydrogen bonds exist.

In the title compound, C13H17N5O2, the dihedral angle angle between the pyrazole and pyridazine rings is 14.44 (8)°. The mol­ecules are linked into a chain along the b axis by C—H⋯O hydrogen bonds.

In the title mol­ecule, C18H18ClN5O2, the central pyrazole ring is perpendicular to the benzene ring and approximately perpendicular to the pyridazine ring [dihedral angles 89.9 (2) and 82.8 (2)°, respectively].

In the title compound, C18H18ClN5O2, there are two independent mol­ecules in the asymmetric unit. In both mol­ecules, the pyrimidine ring is almost coplanar with the central pyrazole ring, while the benzene ring is almost perpendicular to it.

The title compound, C11H9ClN2O2, crystallizes with weak inter­molecular N—H⋯O hydrogen-bond inter­actions. The dihedral angle between the pyrimidine and benzene rings is 86.82 (7)°.

The pyrazolo[1,5-a]pyrimidine ring system of the title compound, C15H12N4S, is essentially planar and the dihedral angle between the plane of the pyrazolo[1,5-a]pyrimidine system and the plane of the phen­yl ring is 134.6 (7)°.

The title mol­ecule, C11H9FN2O, was synthesized from 3,6-difluoro­pyridazine, benz­yl alcohol and sodium hydro­xide in CH3CN under reflux. The asymmetric unit contains two independent mol­ecules with nearly identical geometry. In the crystal structure, the mol­ecules are linked by weak inter­molecular C—H⋯F hydrogen bonds and C—H⋯π inter­actions.

In the title compound, C14H15ClN2O, the benzene and pyrimidine rings are nearly perpendicular, the dihedral angle between them being 84.7 (2)°.

In the crystal structure of the title compound, C9H9ClN4, there are non-classical intramolecular C—H⋯N hydrogen bonds and intermolecular C—H⋯π interactions.

The tetra­hydro­pyrimidine ring of the title mol­ecule, C11H11FN2OS, adopts a half-chair conformation. In the crystal structure, the mol­ecules are linked to form centrosymmetric hydrogen-bonded dimers.

The title compound, C12H16N4O4S, is composed of two substituted pyrazole rings, which are connected through a sulfone group. The dihedral angle between the two pyrazole rings is 79.1 (1)°. The ethoxy­carbonyl substituent is planar and is slightly twisted away from the attached pyrazole ring.

The title compound, C15H13F3N2O, contains one benzene ring, one cyclohexane ring and a pyridazine ring. The dihedral angle formed by the pyridazine ring with the benzene ring is 61.5 (2)°. The crystal structure is stabilized by two intermolecular hydrogen bonds (N—H...O and C—H...F). The cyclohexane ring adopts a screw-boat conformation. The CF3 group is disordered over two positions; the site occupancy factors are ca 0.6 and 0.4.

The title compound, C24H27N3O4, also known as fenpyroximate, is a commercial acaricide. The benzene ring of the phenoxy group is approximately perpendicular to the pyrazole ring with a dihedral angle of 84.37 (11)°. The dihedral angle between the phenoxy and the benzoate benzene rings is 48.83 (8)°.