Supramolecular architecture of theophylline polymorphs, monohydrate and co-crystals with iodine: study from the energetic viewpoint.

The regularities of crystal structure organization were thoroughly studied in all to date known polymorphic modifications of theophylline (THP) using an energetic approach. The monohydrate and a co-crystal of theophylline with one half equivalent of an iodine molecule were similarly investigated. The calculations of pairwise interaction energies have showed that the crystals studied can be divided into two groups according to their basic structural motifs: or .

Towards Amplified Probing of Weak Intermolecular Interactions on the External Surfaces of Molecular Capsules.

We report a sensitive method for comparing weak interactions between aryl rings located on the external surfaces of equilibrating homo- and heterodimeric capsules. Two identical self-complementary resorcin[4]arene tetrabenzoate molecules and one tetramethylammonium cation form in CDCl hydrogen-bonded homodimeric capsules whose exteriors are decorated with four tight pairs of weakly interacting aryl rings. The pair wise mixing of six different homodimers establishes their equilibria with the corresponding heterodimeric species in which two types of aryl rings exert on each other some gentle forces.

Methyl 5-chloro-4-hy-droxy-2,2-dioxo-1-2λ,1-benzo-thia-zine-3-carboxyl-ate: structure and Hirshfeld surface analysis.

The title compound, CHClNOS, which has potential analgesic activity, crystallizes in space group 2/. The benzo-thia-zine ring system adopts an inter-mediate form between sofa and twist-boat conformations. The coplanarity of the ester substituent to the bicyclic fragment is stabilized by an O-H⋯O intra-molecular hydrogen bond.

Automated, Accelerated Nanoscale Synthesis of Iminopyrrolidines.

Miniaturization and acceleration of synthetic chemistry is an emerging area in pharmaceutical, agrochemical, and materials research and development. Herein, we describe the synthesis of iminopyrrolidine-2-carboxylic acid derivatives using chiral glutamine, oxo components, and isocyanide building blocks in an unprecedented Ugi-3-component reaction. We used I-DOT, a positive-pressure-based low-volume and non-contact dispensing technology to prepare more than 1000 different derivatives in a fully automated fashion.

1,3,4-Oxadiazoles by Ugi-Tetrazole and Huisgen Reaction.

Easy to perform, functional group tolerant, and short syntheses of the privileged scaffold oxadiazole are highly desired. Here, a metal-free protocol for MCR-based synthesis of 2,5-disubstituted 1,3,4-oxadiazoles via a Ugi-tetrazole/Huisgen sequence was developed. Optimization and scope and limitations of this short and general sequence are described.

Pd-Catalyzed de Novo Assembly of Diversely Substituted Indole-Fused Polyheterocycles.

Here we describe a facile, tandem synthetic route for indolo[3,2-]quinolinones, a class of natural alkaloid analogues of high biological significance. A Ugi four-component reaction with indole-2-carboxylic acid and an aniline followed by a Pd-catalyzed cyclization yields tetracyclic indoloquinolines in good to moderate yields. Commercially available building blocks yield highly diverse analogues in just two simple steps.

Expedited Route to Fully Substituted Amino-Pyrazole Building Blocks and Their Further Transformations.

We report here an efficient and easily reproducible two-step approach to heterocycle-substituted amino-pyrazoles from heterocyclic acetonitriles and their unprecedented subsequent transformations to fully substituted pyrazoles. Such transformations include regioselective derivatization from polyamino derivatives, formation of tetracyclic compounds in up to 45% overall yield, and deaminative transformations through diazotization, followed by arylation through Suzuki-Miyaura cross-coupling and C-H activation, providing arylated pyrazoles in up to 71% yield over four steps. This strategy allows the swift introduction of significant molecular complexity to a range of scaffolds.

Supramolecular Architecture of Substituted Tetraphenyl-carbo-benzenes from the Energetic Viewpoint.

The use of DFT-calculated energy-vector diagrams (EVDs) featuring the topology of pairwise intermolecular interaction energies is applied to crystals of carbo-benzenes. A homogeneous set of six ideally centrosymmetric tetraphenyl-carbo-benzenes is selected, with various substituents R in para positions: R=4-anisyl, 1-ethyl-2-phenyl-1H-indol-3-yl, 2-chloro-2-(1-ethyl-2-phenyl-1H-indol-3-yl)ethenyl, tetradecyl, and 9,9-dihexyl-9H-fluoren-2-yl, 2-(9,9-dihexyl-9H-fluoren-2-yl)ethynyl. The basic structural motifs (BSMs) of the crystals vary from layers to columns, depending on the size and shape of the substituents R.

Structure and Binding Energy of Double-Stranded A-DNA Mini-helices: Quantum-Chemical Study.

A-DNA is thought to play a significant biological role in gene expression due to its specific conformation and binding features. In this study, double-stranded mini-helices (dA:dT)3 and (dG:dC)3 in A-like DNA conformation were investigated. M06-2X/6-31G(d,p) method has been utilized to identify the optimal geometries and predict physicochemical parameters of these systems.

Structural waters in the minor and major grooves of DNA--a major factor governing structural adjustments of the A-T mini-helix.

The role of microhydration in structural adjustments of the AT-tract in B-DNA was studied at the B97-D/def2-SV(P) level. The (dA:dT)5 complexes with 10 water molecules in minor and 15 water molecules in major grooves were studied. The obtained network of hydrogen bonds revealed the dependence between the groove width and the types of water patterns.

Role of supramolecular synthons in the formation of the supramolecular architecture of molecular crystals revisited from an energetic viewpoint.

Analysis of the strengths and directionality of intermolecular interactions in the crystals containing only one type of supramolecular synthon allows the suggestion of a general classification of molecular crystals depending on type of their basic structural motifs. All crystals may be divided on four classes namely (I) crystals with isotropic packing of the building units; (II) columnar crystals where the basic structural motif (BSM) is a chain/column; (III) layered crystals with layers as the BSM; (IV) columnar-layered crystals containing chains/columns as the primary basic structural motif and layers as the secondary BSM. Taking into account the participation of different supramolecular synthons in the formation of different levels of the organization of molecular crystals, they may be considered as basic (responsible for the formation of molecular complexes as building units of crystals), primary, secondary and auxiliary, which are involved in the agglomeration of molecules in primary or secondary basic structural motifs or in the packing of these motifs, respectively.

Tuning of character of the N-O bond in HONO from covalent to protocovalent by different types of intramolecular interactions.

Quantum-chemical calculations of the H-O-N=O molecule in the equilibrium and transition states and the complexes of the HONO with BH3, study of the intramolecular interactions using NBO theory, and investigation of the electron distribution on the basis of topological analysis of the ELF function clearly indicate the influence of the n-π* conjugation and n-σ* hyperconjugation interactions on a par with exchange repulsion of lone pairs the character of the N-O bond. It is shown that repulsion between lone pairs of oxygen and nitrogen atoms causes the elongation of the N-O bond only but character of this bond remains covalent. The interaction between lone pair of the terminal oxygen atom and antibonding orbital of the N-O bond (n-σ* hyperconjugation) coincides with influence of repulsion and reinforces it changing the character of the N-O bond from covalent to protocovalent.

B-DNA characteristics are preserved in double stranded d(A)3·d(T)3 and d(G)3·d(C)3 mini-helixes: conclusions from DFT/M06-2X study.

We report the results of the first comprehensive DFT study on the d(A)3·d(T)3 and d(G)3·d(C)3 nucleic acid duplexes. The ability of mini-helixes to preserve the conformation of B-DNA in the gas phase and under the influence of such factors as: solvent, uncompensated charge, and counter-ions was evaluated using M06-2X functional with 6-31G(d,p) basis set. The accuracy of the models was ascertained based on their ability to reproduce key structural features of natural B-DNA.

Entropy versus aromaticity in the conformational dynamics of aromatic rings.

Comparison of the results of Car-Parrinello molecular dynamics simulations of isolated benzene, pyrimidine and 1,2,4-triazine molecules reveals that the unusually low population of planar geometry of the benzene ring is caused by entropy effects despite its high aromaticity. The decrease in symmetry of the molecule results in smaller changes in entropy and Gibbs free energy due to out-of-plane deformations of the ring, leading to an increase in the population of planar geometry of the ring. This leads to differences in the topology of potential energy and Gibbs free energy surfaces.

Influence of deuteration and fluorination on the supramolecular architecture of pyridine N-oxide crystals.

To understand how deuterium and fluorine substituents influence the supramolecular architecture of pyridine N-oxide crystals, the crystal structure of 3-fluoropyridine N-oxide (PNO-3F) was determined and the crystal packing motives of non-deuterated pyridine-N-oxide (PNO), partial-deuterated pyridine-N-oxide (PNO-D) and PNO-3F were analyzed based on ab initio quantum-chemical calculations of the intermolecular interaction energy, using the MP2/6-311G(d,p) method. The appearance of the weak-directing substituents deuterium and fluorine leads to significant changes in the crystal organization of the isotropic packing of PNO molecules.

Intra- and intermolecular interactions in the crystals of 3,4-diamino-1,2,4-triazole and its 5-methyl derivative. Experimental and theoretical investigations of charge density distribution.

In this paper intra- and intermolecular interactions in crystals of 3,4-diamino-1,2,4-triazole (DAT) and its 5-methyl derivative (DAMT) were investigated in details by experimental (high-resolution X-ray diffraction) and theoretical (ab initio quantum chemistry (MP2/aug-cc-pvdz), AIM, and NBO) methods. Influence of n-π conjugation and n→σ* hyperconjugation on the geometry of DAT and DAMT molecules was shown. All intermolecular interactions in crystals of the DAT and DAMT including weak X-H···π and mixed X-H···N/X-H···π hydrogen bonds were considered.

Dependence of deformability of geometries and characteristics of intramolecular hydrogen bonds in canonical 2'-deoxyribonucleotides on DNA conformations.

The molecular structure and deformability (with respect to average geometry) of methyl ethers of canonical 2'-deoxyribonucleotides thymidine-5'-phosphate (mTMP), 2-deoxycytidine-5'-phosphate (mCMP), 2-deoxyadenosine-5'-phosphate (mAMP) and 2'-deoxyguanosine-5'-phosphate (mGMP) in different types of DNA have been calculated using B3LYP/cc-pvdz method. Comparison of energy at equilibrium conformations of nucleotides and conformations with torsion angles of backbone fixed to average values for different types of DNA reveals that incorporation of nucleotides to A-DNA macromolecules requires the minimum amount of deformation energy. Therefore, this type of DNA should be the least strained from viewpoint of intramolecular deformations of monomers.