Insights into the occurrence of packing and conformational polymorphs and anhydrous/hydrate forms of 1,2-bis(aminocarbonyl(1-tert-butyl-1H-pyrazol-35-yl))ethanes with the substituents R = Me (a), ...F-4-Ph (b), Cl-4-Ph (c), and Br-4-Ph (d) in positions 5 (1) and 3 (2) of the pyrazole rings are presented. In this series, two molecular forms were observed, linear and folded. Compound 1a revealed an illuminating and rare example of a highly flexible molecule with packing polymorphism. The molecular stacking and absence of NH···OC interactions promoted polymorph growth. Structure 2a showed chains driven by NH···OC bonds in the anhydrous form and closed dimers by water binding the molecules (NHamide···OHwt···COamide) in the hydrate form. Two different forms were observed for conformational polymorph 2d (linear and folded). The folded form was about −10 kcal mol–1 more stable than the linear form, showing significant crystalline packing differences. This occurrence is attributed to the rotation of the amide groups through the NH···OC bonds. The linear shape showed a higher stabilization energy for NH···OC bonds and a cluster −6 kcal mol–1 more stable than polymorph 2dI. Compounds 1b–d and 2b-c also had their crystal growth proposed and features highlighted.
A series of
N
-arylbenzamides containing amide groups and phenyl-perfluorinated rings were used as the smallest molecules to investigate the direct influence of hydrogen bonds and aromatic ...donor-acceptor complementarity in the solid state.
N
-Phenylbenzamide and pentafluoro-
N
-(perfluorophenyl)benzamide were investigated in self-assembly as well as in cocrystal form. Moreover, the respective mixed phenyl-perfluorinated compounds were used in this study. Supramolecular cluster demarcation was used, and crystallization mechanisms were proposed based on the hierarchy of stabilization energies in one-, two-, or three-dimensional growth processes (1D, 2D, or 3D, respectively). At the molecular level, effects such as torsion, planes, and intramolecular interactions showed significant changes compared to the optimized structures, evidencing the supramolecular influence. When considering the supramolecular environment, crystallization mechanisms of the self-assembly of phenyl-phenyl amide offer a 2D → 3D process, whereas the other compounds were classified in a 1D (chains) → 2D (layers) → 3D stepwise process. The interchain links were driven by C-H π interactions in the self-assembly and π π interactions in the mixed compounds and cocrystal packing. QTAIM analysis evidences the importance and contribution of the strong NH O&z.dbd;C hydrogen bond of all crystals. MEP plots highlight the complementarity between amide sites and aromatic rings, helping to understand the cocrystal formation. Lastly, a comparison of the NH O&z.dbd;C bond strength of the cocrystal obtained (−11 kcal mol
−1
) with those of similar cocrystals linked by amide bonds deposited in the CSD showed the highest value of the presented cocrystal. These findings will be helpful in the modulation and design of new molecular solids.
Crystallization mechanisms were proposed to investigate hydrogen bond and aromatic donor-acceptor interactions in a series of phenyl-perfluorophenyl amides. The modulation of NH O&z.dbd;C bonds and aryl complementarity drove a new cocrystal growth.
The supramolecular architectures of amide-containing compounds are highly dependent on the side-chain substituents, although the potential impact of isoxazole substituents on polymorph formation has ...not been thoroughly explored. Hence, three distinct forms of N 1 , N 3 -bis(5-methylisoxazol-3-yl)malonamide (1) were obtained and characterized: two polymorphic forms and one solvate. An in-depth analysis of the interactions and energy content of the crystals based on supramolecular clusters allowed us to propose crystallization mechanisms (crystal retrosynthesis). Specifically, the energy similarities between the interaction of the first sites NH amide ⋯OC amide (form 1I) and the symmetric sites NH amide ⋯N isox (form 1II) were found to contribute to their formation. Nonetheless, the presence of DMSO resulted in the formation of form 1III, where the solvent molecule disrupted amide-amide interactions. The first nuclei are more stable than forms 1I and 1II. The compound of N 1 , N 2 -bis(5-methylisoxazol-3-yl)oxalamide (2) was used as a comparison, and through the absence of polymorphs, revealed that the central carbon in molecule 1 allows a flexible adaptation that leads to the three forms. These findings suggest that variations in solvents, flexibility, and the presence/absence of amide–amide interactions can modulate the competition between amide-containing isoxazole compounds.
Rotaxanes are designated as molecular machines due their different movements. Systematic studies regarding the different conformations adopted by these systems and the factors that lead to the ...distribution of the conformations, in both solution and the solid state, have not been widely explored, especially for rotaxanes with nonsymmetric stoppers. Therefore, in this study we have investigated three novel 2rotaxanes containing threads derived from nonsymmetric succinamides R1R2NC(O)‐CH2CH2‐C(O)NR2R1, with R1/R2 = Bu/Bn, Bu/2‐furylmethyl, and 5‐methylisoxazol‐3‐yl/2‐furylmethyl. The proportions of rotamers were investigated for threads and rotaxanes by solution and solid‐state NMR spectroscopy as well as by single‐crystal and powder X‐ray diffraction. In solution, the threads present different proportions of conformer, with the E,Z conformation prevailing, whereas only one conformer is observed in the solid state. For the rotaxanes, only one conformer prevails in the single crystal, whereas the solution and solid (bulk) states present more than one rotamer. These proportions are modified when the threads are incorporated into the macrocycle during rotaxane formation. The intramolecular interactions in each rotamer were investigated by QTAIM and variable‐temperature 1H NMR experiments. The changes in conformational population between the threads and respective rotaxanes can be explained by a set of different intramolecular interactions, with trifurcated hydrogen bonds responsible for most of the stabilization energy.
A conformational study of rotaxanes has been performed. The proportion of different rotamers was investigated for threads and for threads incorporated into rotaxanes. This investigation was performed by using solution and solid‐state NMR spectroscopy, single‐crystal XRD, and PXRD. How the conformational population is affected when the thread is incorporated into the macrocycle has been evaluated.
An Ullmann-type copper-catalyzed amination coupling reaction has been employed for the synthesis of novel series of 2-aryl-6-(1H-indol-1-yl)-4-(trifluoromethyl)quinolines showing photophysical, ...biomolecule-binding properties (DNA/HSA) and generation of 1O2 species.
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•New 6-(1H-Indol-1-yl)quinolines by Ullmann-type cooper-catalyzed amination reaction.•Photophysical properties by absorption and emission analysis of compounds are studied.•Biomolecule-binding DNA and HSA properties are investigated by spectroscopy assays.
This paper describes the synthesis of a novel series of 2-aryl-6-(1H-indol-1-yl)-4-(trifluoromethyl)quinolines, in which aryl = C6H5, 4-CH3C6H4, 4-FC6H4, 4-CF3C6H4 and heteroaryl = 2-thienyl, by an Ullmann-type cooper-catalyzed amination cross-coupling reaction. Photophysical properties of indolyl-quinolines were investigated using absorption and emission analysis. The emission fluorescence analysis showed a blue to cyan region emission in the 400–650 nm range. Large Stokes shifts values were observed for all new quinolines and attributed to the ICT state and to the electron-substituent properties. The ability to generate 1O2 species after being exposed to white light and biomolecule-binding DNA / HSA properties were also investigated.
The crystallization of a series of 1-(4-halophenyl)-3-phenyltriazenide N 1-oxides ( 1–4 ) and 1-(phenyl)-3-phenyltriazenide N 1-oxide ( 5 ) was evaluated using the supramolecular cluster approach. ...This method is an efficient tool to assess the crystallization mechanism of compounds and, consequently, the steps involved in crystal formation. Compounds 1 and 4 show crystallization in two main steps while compounds 2 and 3 present three main steps, in which column formation occurs in the first step. The crystallization process for 5 occurs in 3 main steps, starting from a robust dimer formation (−16.82 kcal mol −1 ). Two new parameters – N CG % (topological and energetic contribution percentage) and NG/NC (energetic parameter/topological parameter ratio) – assisted in the interpretation of crystal growth. Compounds 1–4 showed N CG % = 50 in the first step while compound 5 reached only 50% of the contribution in the second step. The differences in N CG % were attributed to strong hydrogen bonds in the non-halogenated compound. The dominant parameter in each step of the crystallization process was indicated by the NG/NC parameter. The crystallization mechanism in all compounds was initially driven by an energetic process followed by a topological process. The existence of X⋯π interactions was shown and was observed to be a consequence of a topological process and without any major contributions to crystal formation. Thermal analysis and UV-vis spectral data were also discussed regarding the properties of these compounds.
An efficient synthesis methodology for a series of tetrazolo1,5-
pyrimidines substituted at the 5- and 7-positions from the cyclocondensation reaction CCC + NCN was developed. The NCN corresponds to ...5-aminotetrazole and CCC to β-enaminone. Two distinct products were observed in accordance with the β-enaminone substituent. When observed in solution, the compounds can be divided into two groups: (a) precursor compounds with R = CF
or CCl
, which leads to tetrazolo1,5-
pyrimidines in high regioselectivity with R at the 7-position of the heterocyclic ring; and (b) precursor compounds with R = aryl or methyl, which leads to a mixture of compounds, tetrazolo1,5-
pyrimidines (R in the 5-position of the ring) and 2-azidopyrimidines (R in the 4-position of the ring), which was attributed to an equilibrium of azide-tetrazole. In the solid state, all compounds were found as 2-azidopyrimidines. The regiochemistry of the reaction and the stability of the products are discussed on the basis of the data obtained by density functional theory (DFT) for energetic and molecular orbital (MO) calculations.
A series of 5(3)-aryl-3(5)-carboxyethyl-1-
tert
-butylpyrazoles (aryl, 4-X-C
6
H
4
, where X = H, F, Cl and Br) were studied in the solid state. The 1,3-regioisomers (carboxyethyl group in ...3-position) of
t
-butylpyrazoles crystalized in three different forms: s-
cis
, s-
trans
or s-
cis
+ s-
trans
. On the other hand, the 1,5-regioisomers (carboxyethyl group in 5-position) of
t
-butylpyrazoles showed only s-
trans
conformation. The
13
C CPMAS and SCXRD data confirmed that each 1,3- and 1,5-regioisomers of
t
-butylpyrazoles crystallized only one of the three mentioned forms. The potential energy surface (PES) yielded insights regarding the formation of each conformer. In general, quantum mechanical calculations showed that the conformer s-
trans
is more stable than s-
cis
, and the calculated stability difference was 0.7 kcal mol
−1
for the 1,3-regioisomers and 3.5 kcal mol
−1
for the 1,5-regioisomers. Moreover, 1,5-regioisomers of
t
-butylpyrazoles showed intramolecular interactions of type CH⋯OC between the carbonyl and
t
-butyl group, which was obtained by QTAIM analysis. This interaction can influence the stabilization for s-
trans
conformation in the solid state. In contrast, the 1,3-regioisomers did not show intramolecular interaction with the COOEt group, and the conformation adopted in the solid state should be the consequence of the crystalline packing. The QTAIM analysis of the more stable dimers of s-
trans
-conformation for X = Cl, Br showed that the halogen atoms interact with the COOEt group, helping stabilize this conformation. On the other hand, in the s-
cis
⋯s-
cis
conformation dimer (X = Cl, Br), the COOEt group was stabilized by the phenyl group, which is the same stabilization for X = H.
A series of seven N-phenylamides R–C(O)NHPh, in which R: CH3, C(CH3)3, Ph, CF3, CCl3, CBr3, and H were used as models in this study. Molecular packing and intermolecular interactions were ...evaluated by theoretical calculations, solution NMR, and quantum theory of atoms in molecules analyses. Crystallization mechanisms were proposed based on the energetic and topological parameters using the supramolecular cluster as demarcation. Concentration-dependent 1H NMR experiments corroborated the proposed interactions between molecules. For all compounds (except for R: H, which initially formed tetramers), layers (two-dimensional) or chains (one-dimensional) were formed in the first stage of the proposed crystallization mechanisms. The presence of strong intermolecular NH···OC interactions promoted the first stages. The study in solution provided different values of association constant (K ass) governed by the hydrogen bond NH···OC, showing that the stronger interactions are directly influenced by the substituent steric hindrance. A correlation between K ass(NH···OC) from the solution and the NH···OC interaction energy in the crystal showed a good trend.
A series of seven 5-aryl-1-(1,1-dimethylethyl)-3-trifluoromethyl-1H-pyrazoles in which aryl: C6H5 (1); C6H4-4-F (2); C6H4-4-Cl (3); C6H4-4-Br (4); C6H4-4-I (5); C6H4-4-CH3 (6), C6H4-4-OCH3 (7) and ...5-aryl-1-(1,1-dimethylethyl)-1H-pyrazole C6H4-4-NO2 (8) was studied at the molecular and supramolecular level. X-ray diffraction, thermal analysis, sublimation enthalpy data, NMR spectroscopy, and DFT calculations were used in this systematic study. The supramolecular cluster was used as demarcation and furnished energetic and contact area data of each compound, which allowed proposals of crystallization mechanisms. Two different mechanisms were observed: (i) compounds 1–4 had 2 stages, where initially the monomers formed a 2-D block, followed by the formation of the 3-D block; (ii) compounds 5–8 also had 2 stages, where initially the monomers formed a 1-D block, followed by formation of the 3-D block. The packing observed in the crystal was corroborated by data from 1H NMR experiments. The types of interactions observed were evaluated using Hirshfeld surface and QTAIM analysis and showed slight differences in both methods. Lastly, energetic and topologic data obtained from the clusters were correlated with crystal properties such as crystal packing efficiency, sphericity, and sublimation enthalpy and presented good trends between data.
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