Antimicrobial properties of novel ionic liquids derived from imidazolium cation with phenolic functional groups.

Bacterial infections are nowadays among the major threats to public health worldwide. Thus, there is an urgent and increased need for new antimicrobial agents. As a result, the exploration of the antimicrobial properties of different substances including ionic liquids (ILs) has recently attracted great attention. The present work is aimed at evaluating how the addition of halogens and hydrophobic substituents on alkylimidazolium units of ILs as well as the increase in their chain lengths affects the antimicrobial properties of such ILs. After their synthesis, the antibacterial activities of these compounds against Pseudomona aeruginosa, Escherichia coli, and Staphylococcus aureus are determined by measuring their minimal inhibitory concentrations (MICs). Key features in ILs-membrane interactions are also studied using long-term all-atom molecular dynamics simulations (MDs). The results show that these ILs have good antibacterial activity against S. aureus, E. coli, and P. aeruginosa, with MIC values range from <7.81 to 62.50 µM. The antimicrobial property of tert-butyl N-methylphenolimidazolium salts (denoted as 8b and 8c) is particularly better with MIC values of < 7.81 µM. The antibacterial efficacy is also found to depend on the alkyl chain length and substituents on the phenolic ring. Finally, MDs done for ILs in a phosphatidylcholine (POPC) bilayer show key features in the mechanism of IL-induced membrane disruption, where the ILs are inserted as clusters into one side of the bilayer until saturation is reached. This insertion increases "leaflet strain" up to critical threshold, likely triggering the morphological disruption of the membranes in the microbes.

6,6'-Dimethyl-2,2'-[imidazolidine-1,3-diyl-bis(methyl-ene)]diphenol.

In the title compound, C19H24N2O2, a di-Mannich base derived from 2-methyl-phenol and 1,3,6,8-tetra-aza-tri-cyclo-[4.4.1.1(3,8)]dodecane, the imidazolidine ring adopts a twist conformation, with a twist about the ring N-C bond [C-N-C-C torsion angle = -44.34 (14)°]. The two 2-hy-droxy-3-methyl-benzyl groups are located in trans positions with respect to the imidazolidine fragment. The structure displays two intra-molecular O-H⋯N hydrogen bonds, which each form an S(6) ring motif. In the crystal, the mol-ecules are linked by weak C-H⋯O inter-actions with a bifurcated acceptor, forming a three-dimensional network.

4,4'-Di-tert-butyl-2,2'-[imidazolidine-1,3-diylbis(methyl-ene)]diphenol.

In the title compound, C25H36N2O2, the two tert-butyl-substituted benzene rings are inclined at an angle of 53.5 (3)° to one another. The imidazolidine ring has an envelope conformation with with one of the C atoms of the ethylene fragment as the flap. The structure displays two intra-molecular O-H⋯N hydrogen bonds that generate S(6) ring motifs. The crystal studied was a non-merohedral twin with a fractional contribution of 0.281(6) for the minor domain.

4,4'-Dimethyl-2,2'-[imidazolidine-1,3-diylbis(methyl-ene)]diphenol.

The imidazolidine ring in the title compound, C(19)H(24)N(2)O(2), adopts a twist conformation and its mean plane (r.m.s. deviation = 0.19 Å) makes dihedral angles of 72.38 (9) and 71.64 (9)° with the two pendant aromatic rings. The dihedral angle between the phenyl rings is 55.94 (8)°. The mol-ecular structure shows the presence of two intra-molecular O-H⋯N hydrogen bonds between the phenolic hydroxyl groups and N atoms with graph-set motif S(6). In the crystal, C-H⋯O hydrogen bonds lead to the formation of chains along the b-axis direction.

4,4'-Difluoro-2,2'-[imidazolidine-1,3-diylbis(methyl-ene)]diphenol.

In the title compound, C(17)H(18)F(2)N(2)O(2), the imidazolidine ring system exists in a twist conformation. The mean plane through this ring system forms dihedral angles of 80.8 (8)° and 66.2 (13)°, with the benzene rings. The dihedral angle between the benzene rings is 52.0 (14)°. Two intra-molecular O-H⋯N hydrogen bonds each generate S(6) ring motifs. In the crystal, weak C-H⋯O hydrogen bonds form dimers, which are connected by further C-H⋯O inter-actions.

2,2'-[Imidazolidine-1,3-diylbis(methyl-ene)]diphenol.

In the title mol-ecule, C(17)H(20)N(2)O(2), the imidazolidine ring adopts a twist conformation. The mean plane through the five atoms of the imidazolidine ring makes dihedral angles of 70.18 (4) and 74.14 (4)° with the planes of the two aromatic rings. The dihedral angle between the benzene rings is 53.11 (5)°. Both phenol -OH groups form intra-molecular hydrogen bonds to the N atoms, with graph-set motif S(6). In the crystal, pairs of O-H⋯O hydrogen bonds link the mol-ecules into dimers with R(4) (4)(18) ring motifs. The crystal packing is further stabilized by C-H⋯O and weak C-H⋯π inter-actions.

Spirocyclic derivatives as antioxidants: a review.

In recent years, spiro compounds have attracted significant interest in medicinal chemistry due to their numerous biological activities attributed primarily to their versatility and structural similarity to important pharmacophore centers. Currently, the development of drugs with potential antioxidant activities is of great importance since numerous investigations have shown that oxidative stress is involved in the development and progression of numerous diseases such as cancer, senile cataracts, kidney failure, diabetes, high blood pressure, cirrhosis, and neurodegenerative diseases, among others. This article provides an overview of the synthesis and various antioxidant activities found in naturally occurring and synthetic spiro compounds. Among the antioxidant activities reviewed are DPPH, ABTS, FRAP, anti-LPO, superoxide, xanthine oxidase, peroxide, hydroxyl, and nitric oxide tests, among others. Molecules that presented best results for these tests were spiro compounds G14, C12, D41, C18, C15, D5, D11, E1, and C14. In general, most active compounds are characterized for having at least one oxygen atom; an important number of them (around 35%) are phenolic compounds, and in molecules where this functional group was absent, aryl ethers and nitrogen-containing functional groups such as amine and amides could be found. Recent advances in the antioxidant activity profiles of spiro compounds have shown that they have a significant position in discovering drugs with potential antioxidant activities.

Crystal structure of the di-Mannich base 4,4'-di-chloro-3,3',5,5'-tetra-methyl-2,2'-[imidazolidine-1,3-diylbis(methyl-ene)]diphenol.

The title compound, C21H26Cl2N2O2, was prepared in a solvent-free microwave-assisted synthesis, and crystallizes in the ortho-rhom-bic space group Pna21. The imidazolidine ring adopts an envelope conformation and its mean plane is almost perpendicular to the two pendant aromatic rings [dihedral angles = 84.61 (9) and 86.54 (9)°]. The mol-ecular structure shows the presence of two intra-molecular O-H⋯N hydrogen bonds between the phenolic hy-droxy groups and imidazolidine N atoms. The two 3-chloro-6-hy-droxy-2,4-di-methyl-benzyl groups are located in a cis orientation with respect to the imidazolidine fragment. As a result, the lone pairs of electrons on the N atoms are presumed to be disposed in a syn conformation. This is therefore the first example of an exception to the 'rabbit-ears' effect in such 2,2'-[imidazolidine-1,3-diylbis(methyl-ene)]diphenol derivatives.

Repellent activity of essential oils: a review.

Currently, the use of synthetic chemicals to control insects and arthropods raises several concerns related to environment and human health. An alternative is to use natural products that possess good efficacy and are environmentally friendly. Among those chemicals, essential oils from plants belonging to several species have been extensively tested to assess their repellent properties as a valuable natural resource. The essential oils whose repellent activities have been demonstrated, as well as the importance of the synergistic effects among their components are the main focus of this review. Essential oils are volatile mixtures of hydrocarbons with a diversity of functional groups, and their repellent activity has been linked to the presence of monoterpenes and sesquiterpenes. However, in some cases, these chemicals can work synergistically, improving their effectiveness. In addition, the use of other natural products in the mixture, such as vanillin, could increase the protection time, potentiating the repellent effect of some essential oils. Among the plant families with promising essential oils used as repellents, Cymbopogon spp., Ocimum spp. and Eucalyptus spp. are the most cited. Individual compounds present in these mixtures with high repellent activity include alpha-pinene, limonene, citronellol, citronellal, camphor and thymol. Finally, although from an economical point of view synthetic chemicals are still more frequently used as repellents than essential oils, these natural products have the potential to provide efficient, and safer repellents for humans and the environment.