Cyclohexyl Group Research Articles

Reactivity of Cations and Zwitterions Formed in Photochemical and Acid-Catalyzed Reactions from m-Hydroxycycloalkyl-Substituted Phenol Derivatives.

Three m-substituted phenol derivatives, each with a labile benzylic alcohol group and bearing either protoadamantyl 4, homoadamantyl 5, or a cyclohexyl group 6, were synthesized and their thermal acid-catalyzed and photochemical solvolytic reactivity studied, using preparative irradiations, fluorescence measurements, nanosecond laser flash photolysis, and quantum chemical calculations. The choice of m-hydroxy-substitution was driven by the potential for these phenolic systems to generate m-quinone methides on photolysis, which could ultimately drive the excited-state pathway, as opposed to forming simple benzylic carbocations in the corresponding thermal route. Indeed, thermal acid-catalyzed reactions gave the corresponding cations, which undergo rearrangement and elimination from 4, only elimination from 5, and substitution and elimination from 6. On the other hand, upon photoexcitation of 4-6 to S1 in a polar protic solvent, proton dissociation from the phenol, coupled with elimination of the benzylic OH (as hydroxide ion) gave zwitterions (formal m-quinone methides). The zwitterions exhibit reactivity different from the corresponding cations due to a difference in charge distribution, as shown by DFT calculations. Thus, protoadamantyl zwitterion has a less nonclassical character than the corresponding cation, so it does not undergo 1,2-shift of the carbon atom, as observed in the acid-catalyzed reaction.

Crystalline state photochromism of 3-furylfulgides: impact of size and bond flexibility of the non-aromatic alkylidene group.

3-Furylfulgides are photochromic compounds showing high thermal stability in their closed forms. However, their photochromic properties in the solid state should be improved further to fabricate molecular devices. Understanding how the size and the flexibility of the non-aromatic alkylidene moiety alter the crystalline state photochromic properties is also important here, as the alkylidene group is directly involved in the photochromic ring closing and opening reactions. The synthesis of four 3-furylfulgides composed of different alkylidene groups (rigid isopropyl, flexible 2-butyl, rigid cyclopentyl and flexible cyclohexyl), their crystal structures and structure-photochromic property correlation in the crystalline state are reported here. Crystallographic data along with reaction cavity volumes calculated using the program CAVITY [Ohashi et al. (1981), J. Am. Chem. Soc. 103, 5805-5812] disclosed that fulgides with flexible groups at the ring closing site have more free volume around the reactive area in the crystal lattice, which can provide more space for the atomic movements in the reaction and flexibility can reduce the strain built up in the closed C-isomers by making conformations. According to UV-vis spectroscopic data, a higher yield of C-isomers and a better fatigue resistance were obtained for the 3-furylfulgide with the largest and flexible cyclohexyl group showing greater photochromic properties in the crystalline state than the fulgide containing the smallest and rigid isopropyl group.

Kinetic Hydrate Inhibitors: Structure–Activity Relationship Studies on a Series of Branched Poly(ethylene citramide)s with Varying Lipophilic Groups

Novel citric-acid-based polyamides were synthesized by polycondensation reactions using tributyl citrate (TBC) and ethylene diamine (EDA), producing hyperbranched poly(ethylene citramide)s with NH2 termini, which were functionalized with isopropyl, n-butyl, and cyclohexyl groups via the urea group. Characterization was carried out by 1H and 13C nuclear magnetic resonance (NMR) spectroscopic techniques. Molecular weights in this polymer family varied from 3000 to 10 000 Da. The activity of this polymer family as gas hydrate kinetic inhibitors (KHIs) was evaluated for the first time. Constant cooling (1 °C/h) experiments were carried out in high-pressure steel rocking cells using a synthetic natural gas that preferentially forms structure II gas hydrates. The best KHI performance was given by poly(ethylene citramide) CONHCyHe with pendant N-cyclohexyl groups (Mn = 5.65 × 103, and Mw = 1.14 × 104). A structure–activity relationship (SAR) analysis of the KHI test results supports the hypothesis that increasin...

Синтез и биологическая активность гидрохлоридов 1-(4-замещенных фенил)-1-алкил(арил)-2-фенил- 3-аминопропан-1-олов

Аминометилированием 1-(4-замещенных фенил)-2-фенилэтанонов с параформальдегидом и амином в среде этанола получены α-фенил-β-амино-4-замещенные пропиофеноны. Взаимодействием последних с реактивами Гриньяра в среде эфира получены третичные аминопропан-1-олы и их гидрохлориды. Показано достаточно эффективное, но различное ингибирование аденозиндезаминазы (АДА, К.Ф.3.5.4.4), одного из ключевых ферментов пуринового обмена синтезированными соединениями. Отмечена взаимосвязь «структура — активность» для ингибирования АДА. Исследование антибактериальной активности синтезированных соединений показало ее полное отсутствие для большинства соединений, и наличие умеренной антибактериальной активности в отношении грамположительных микроорганизмов только у соединений Vа, Vг и VIг.

Improving water solubility of nateglinide by complexation of β-cyclodextrin

Inclusion complex of anionic nateglinide (NTG) with β-cyclodextrin (βCD) has been prepared to improve the water solubility of NTG. The mechanism of the complexation was elucidated using isothermal titration calorimetry and molecular modeling study. The solubility of NTG increased linearly with increasing the concentration of βCD and decreased gradually over 6 mM βCD in the solution. The maximum solubility of NTG in the presence of βCD was nine times more than that of NTG only. The stoichiometry (n), association constant (K), and thermodynamic parameters (ΔG, ΔH, ΔS) for the complexation were estimated: n = 1.0, K = 5.8 × 103 M−1, ΔG = −21.5 kJ mol−1, ΔH = −15.7 kJ mol−1, and ΔS = 19.5 J mol−1 K−1 at pH 7.0 and 298.15 K. The conformations and solvation energies for two types of the inclusion complex, type A penetrating the isopropyl cyclohexyl group of NTG into the βCD cavity and type B penetrating the phenyl group of NTG, were calculated. It was indicated that anionic NTG could strongly form the inclusion complex of type A complex with βCD at 1:1 molar ratio to increase the solubility in aqueous solution.

Degradation of abamectin by newly isolated Stenotrophomonas maltophilia ZJB-14120 and characterization of its abamectin-tolerance mechanism

An abamectin (ABM)-degrading bacterium, Stenotrophomonas maltophilia ZJB-14120, was isolated and identified. This strain is capable of degrading 84.82% of ABM at an initial concentration of 200 mg/L over a 48 h incubation period. This strain showed efficient biodegradation ability (7.81 mg/L/h) to ABM and high tolerance (1000 mg/L) to all macrolides tested. In addition to ABM, emamectin, erythromycin and spiramycin can also be degraded by this strain. Modifications involving either reduction of the double bond between C22–C23 or replacement of the C25-group of ABM with a cyclohexyl group can completely inhibit biodegradation of ABM. The ABM-degrading capability of strain ZJB-14120 is likely to be intrinsic to its metabolism and could be inhibited by incubating with erythromycin, azithromycin, spiramycin or rifampicin. A new and successive degradation pathway was proposed based on metabolite analysis. Although there is evidence for metabolite inhibition, this strain has high ABM degradation activity and reusability. Further investigation showed that activated macrolide efflux pump(s) and an undetermined mechanism for regulating the intracellular ABM concentration are responsible for normal uptake of essential metabolites while pumping out excess harmful compounds. Strain ZJB-14120 may provide efficient treatment of water and soil contaminated by toxic levels of abamectin and emamectin.

Exploration of benzamidochromenone derivatives with conformational restrictor as interleukin-5 inhibitors

Novel amidochromen-4-one analogs 8a–k and 9a–f were prepared and studied for their IL-5 inhibitory activity. Among the synthesized compounds, (6-benzamido-2-cyclohexyl-4-oxo-4H-chromen-3-yl)methyl acetate (8a, 95% inhibition at 30μM, IC50=6.1μM) exhibited potent IL-5 inhibitory activity. The conformational restrictor at position 2 like bulky cyclohexyl group is favorable for the formation of effective conformer of side chain small ester like acetoxymethyl at position 3 of these chromenone analogs 8. In addition the hydrophobic planarity of benzamido group at position 6 should be important for the potent IL-5 inhibitory activity. Since replacing acetoxymethyl moiety with hydroxymethyl group at position 3 of chromenone decreases the activity, which indicates that the location of hydrogen bonding group should be near 4 atom distances away from chromenone ring is more optimum for the activity. Therefore, these benzamidochromen-4-one analogs 8 are novel scaffold for finding potent interleukin-5 inhibitors.

Fused-ring structure of decahydroisoquinolin as a novel scaffold for SARS 3CL protease inhibitors

The design and evaluation of a novel decahydroisoquinolin scaffold as an inhibitor for severe acute respiratory syndrome (SARS) chymotrypsin-like protease (3CLpro) are described. Focusing on hydrophobic interactions at the S2 site, the decahydroisoquinolin scaffold was designed by connecting the P2 site cyclohexyl group of the substrate-based inhibitor to the main-chain at the α-nitrogen atom of the P2 position via a methylene linker. Starting from a cyclohexene enantiomer obtained by salt resolution, trans-decahydroisoquinolin derivatives were synthesized. All decahydroisoquinolin inhibitors synthesized showed moderate but clear inhibitory activities for SARS 3CLpro, which confirmed the fused ring structure of the decahydroisoquinolin functions as a novel scaffold for SARS 3CLpro inhibitor. X-ray crystallographic analyses of the SARS 3CLpro in a complex with the decahydroisoquinolin inhibitor revealed the expected interactions at the S1 and S2 sites, as well as additional interactions at the N-substituent of the inhibitor.

Aqua substitution by biologically relevant nucleophiles in dinuclear platinum(II) complexes linked by diamino linkers with cyclohexyl groups

Substitution of the aqua ligand from three platinum(II) complexes, namely [Pt(H2O)(N,N-bis(2-pyridylmethyl)cyclohexylamine](ClO4)2 (Pt1); [{Pt(H2O)}2(N,N,N′,N′-tetrakis(2-pyridylmethyl)-trans-1,4-cyclohexyldiamine)](ClO4)4 (Pt2); and [{Pt(H2O)}2(N,N,N′,N′-tetrakis(2-pyridylmethyl)-4,4′-ethylenedicyclohexyldiamine)](ClO4)4 (Pt3), by three biologically relevant nucleophiles [viz., glutathione (Glu); DL-penicillamine (Pen); and l-histidine (His)] was studied in aqueous 0.1 M perchloric acid medium. The substitutions were investigated under pseudo-first-order conditions as a function of nucleophile concentration and temperature using UV–visible spectrophotometry. The reactions of these complexes with the nucleophiles proceeded via a single step whose reactivity decreased in the order: Pt1 > Pt3 > Pt2 and was controlled by steric and electronic influences of the complexes. Sulfur donor nucleophiles (Glu and Pen) reacted much faster than the nitrogen bearing His, with Glu appearing to be more nucleophilic than Pen. The large and negative activation entropies and low but positive enthalpies of activation affirm an associative mode of activation.

Synthesis and evaluation of antimitotic activity of new tetralone acid analogues of podophyllotoxin

The new tetralone acids (7a-e) were synthesized as analogues of podophyllotoxin. They were prepared by replacing 3,4,5-trimethoxyphenyl ring with cyclohexyl group in podophyllotoxin and 1,3-methylene dioxy ring with methoxy, hydrogen, methyl, thiomethyl, and fluorine atoms. The analogues of podophyllotoxin were synthesized using Gensler’s method with some changes in reagents and experimental procedure. The structures of the synthesized compounds were confirmed by IR, 1 H NMR, 13 C NMR, mass spectra and elemental analysis data. The synthesized tetralones acids were screened for their antimitotic activity. It is noteworthy that compound 7b possessed excellent antimitotic activity, 7c and 7e showed considerable activity and remaining 7a and 7d possessed low activity.

Crystal structure of 4-cyclo-hexyl-1-(propan-2-yl-idene)thio-semicarbazide.

In the title compound, C10H19N3S, the cyclo­hexyl group adopts a chair conformation and adopts a position approximately syn to the thione S atom. The CN2S thio­urea moiety makes dihedral angle of 13.13 (10)° with the propan-2-yl­idene­amino group. An intra­molecular N—H⋯N hydrogen bond is noted. In the crystal, inversion dimers linked by pairs of N—H⋯S hydrogen bonds generate R 2 2(8) loops.

Self-assembled monolayers of cyclohexyl-terminated phosphonic acids as a general dielectric surface for high-performance organic thin-film transistors.

A novel self-assembled monolayer (SAM) on AlOy /TiOx is terminated with cyclohexyl groups, an unprecedented terminal group for all kinds of SAMs. The SAM-modified AlOy /TiOx functions as a general dielectric, enabling organic thin-film transistors with a field-effect mobility higher than 5 cm(2) V(-1) s(-1) for both holes and electrons, good air stability with low operating voltage, and general applicability to solution-processed and vacuum-deposited n-type and p-type organic semiconductors.

Influence of substituents on conformational preferences of helix foldamers of γ‐dipeptides

Conformational preferences of 9- and 14-helix foldamers have been studied for γ-dipeptides of 2-aminocyclohexylacetic acid (γAc6 a) residues such as Ac-(γAc6 a)2 -NHMe (1), Ac-(C(α) -Et-γAc6 a)2 -NHMe (2), Ac-(γAc6 a)2 -NHBn (3), and Ac-(C(α) -Et-γAc6 a)2 -NHBn (4) at the M06-2X/cc-pVTZ//M06-2X/6-31 + G(d) level of theory to explore the influence of substituents on their conformational preferences. In the gas phase, the 9-helix foldamer H9 and 14-helix foldamer H14-z are found to be most preferred for dipeptides 2 and 4, respectively, as for dipeptides 1 and 3, which indicates no remarkable influence of the C(α) -ethyl substitution on conformational preferences. The benzyl substitution at the C-terminal end lead H14-z to be the most preferred conformer for dipeptides 3 and 4, whereas it is H9 for dipeptides 1 and 2, which can be ascribed to the favored CH···π interactions between the cyclohexyl group of the first residue and the C-terminal benzyl group. There are only marginal changes in backbone structures and the distances and angles of H-bonds for all local minima by C(α) -ethyl and/or benzyl substitutions. Although vibrational frequencies and intensities of the dipeptide 4 calculated at both M06-2X/6-31 + G(d) and M05-2X/6-31 + G(d) levels of theory are consistent with observed results in the gas phase, H14-z is predicted to be most preferred by ΔG only at the former level of theory. Hydration did not bring the significant changes in backbone structures of helix foldamers for both dipeptide 1 and 4. It is expected that the different substitutions at the C-terminal end lead to the different helix foldamers, which may increase the resistance of helical structures to proteolysis and provide the more surface to the helical structures suitable for molecular recognition.

Crystal structure of N-[4-amino-5-cyano-6-(methyl-sulfan-yl)pyridin-2-yl]-2-(cyclo-hexyl-sulfan-yl)acetamide.

In the title mol­ecule, C15H20N4OS2, the acetamido fragment is nearly coplanar with the pyridyl ring [C—N—C—C torsion angle = −4.1 (2)°], while the cyclo­hexyl­sulfanyl portion protrudes from this plane [N—C—C—S torsion angle = −40.8 (6)°]. In the crystal, alternating pairwise N—H⋯O and N—H⋯N hydrogen bonds across inversion centres form chains along [101], which are associated into stepped layers via offset π–π stacking between pyridyl rings [centroid–centroid distance = 3.566 (1) Å]. The cyclo­hexyl group and the two atoms of the S—C bond attached to it are disordered over two sets of sites with site-occupancy factors of 0.8845 (18) and 0.1155 (18).

Novel silicon(IV) phthalocyanines containing piperidinyl moieties: Synthesis and in vitro antifungal photodynamic activities

A new series of silicon(IV) phthalocyanines (SiPcs) axially di-substituted with piperidinyl moieties (compounds 1, 2a, and 3a) and their N-methylated derivatives (compounds 2b and 3b) have been synthesized and characterized. Meanwhile, an analogue di-substituted with cyclohexyl groups (compound 4) has also been prepared as a control. The antifungal photoactivities of these SiPcs toward Candida albicans were found to follow the order: 2b ＞ 3a ≈ 3b ＞ 1 ≈ 2a ＞ 4. The structure–activity relationship of these phthalocyanines has been discussed by investigating their photophysical and photochemical properties, partition coefficient, and cellular uptake. The cationic phthalocyanine 2b shows the highest photodynamic activity against C. albicans causing 4 log10 reduction of this fungus at 100 μM, which could be attributed to its high singlet oxygen yields, less aggregation in aqueous media, and relatively efficient cellular uptake.

Thermophysical Properties of Imidazolium-Based Ionic Liquids: The Effect of Aliphatic versus Aromatic Functionality

In this work, a series of imidazolium-based ionic liquids with varying functionalities from aliphatic to aromatic groups and a fixed anion, bis[(trifluoromethane)sulfonyl]amide, were investigated. The imidazolium cations included 1-heptyl-3-methylimidazolium, 1-(cyclohexylmethyl)-3-methylimidazolium, 1-benzyl-3-methylimidazolium, 1,3-dibenzylimidazolium, and 1-(2-naphthylmethyl)-3-methylimidazolium. Structure–property relationships were investigated regarding the substituent effects on the imidazolium cation, including n-alkyl versus cycloalkyl and aromatic versus aliphatic, as well as the effects of cation symmetry and larger aromatic polycyclic functionalities. Thermophysical properties investigated include density, thermal transition temperatures, and decomposition temperatures. The densities of the ionic liquids are governed by the substituents on the cation: n-alkyl < cycloalkyl < aromatic. The group contribution method is applicable for the density estimation of ionic liquids, and the volume parameters for cyclohexyl, phenyl, and naphthyl groups are reported. The glass transition temperature (Tg) follows the same systematic trend due to substituent flexibility: n-alkyl < cycloalkyl < aromatic. Thermal stability as measured by dynamic thermogravimetric analysis (TGA) is not strongly affected by the substituents on the imidazolium ring; however, slight differences are observed with the higher Tg ionic liquids having lower decomposition temperatures for this series of ionic liquids. On the other hand, the cyclohexylmethyl-substituted ionic liquid exhibits a higher activation energy for degradation than the other ionic liquids based on isothermal TGA, and all ionic liquids studied show significant weight loss at 300 °C indicating that appreciable decomposition can occur at temperatures substantially lower than the onset temperature observed in dynamic TGA scans.

Studies on [PtCl2 ]- or [AuCl]-catalyzed cyclization of 1-(Indol-2-yl)-2,3-allenols: the effects of water/steric hindrance and 1,2-migration selectivity.

The [PtCl2 ]- or [AuCl]-catalyzed reaction of 1-(indol-2-yl)-2,3-allenols occurred smoothly at room temperature to afford a series of poly-substituted carbazoles efficiently. Compared with the [PtCl2 ]-catalyzed process, the [AuCl]-catalyzed reaction represents a significant advance in terms of the scope and the selectivity. Selective 1,2-alkyl or aryl migration of the gold carbene intermediate was observed: compared with the methyl group, the isopropyl, cyclopropyl, cyclobutyl, and cyclohexyl groups migrate exclusively; the cyclopropyl group shifts selectively over the ethyl group; the 1,2-migration of a non-methyl linear alkyl is faster than methyl group; the phenyl group migrates exclusively over methyl or ethyl group. DFT calculations show that water makes the elimination of H2 O facile requiring a much lower energy and validates the migratory preferences of different alkyl or phenyl groups observed.

Poly-lysine peptidomimetics having potent antimicrobial activity without hemolytic activity.

Diversity of sequence and structure in naturally occurring antimicrobial peptides (AMPs) limits their intensive structure-activity relationship (SAR) study. In contrast, peptidomimetics have several advantages compared to naturally occurring peptide in terms of simple structure, convenient to analog synthesis, rapid elucidation of optimal physiochemical properties and low-cost synthesis. In search of short antimicrobial peptides using peptidomimetics, which provide facile access to identify the key factors involving in the destruction of pathogens through SAR study, a series of simple and short peptidomimetics consisting of multi-Lys residues and lipophilic moiety have been prepared and found to be active against several Gram-negative and Gram-positive bacteria containing methicillin-resistant Staphylococcus aureus (MRSA) without hemolytic activity. Based on the SAR studies, we found that hydrophobicity, +5 charges of multiple Lys residues, hydrocarbon tail lengths and cyclohexyl group were crucial for antimicrobial activity. Furthermore, membrane depolarization, dye leakage, inner membrane permeability and time-killing kinetics revealed that bacterial-killing mechanism of our peptidomimetics is different from the membrane-targeting AMPs (e. g. melittin and SMAP-29) and implied our peptidomimetics might kill bacteria via the intracellular-targeting mechanism as done by buforin-2.

Reactions of silver thiolates with bidentate phosphanes

A series of reactions of different silver thiolates, AgSR (R=Mes (mesityl), Nph (naphthyl), Cy (cyclohexyl)), with bidentate phosphanes was performed yielding a bunch of new compounds, which were characterized by single crystal X-ray diffraction.Depending on the nature of the thiolate and the phosphane the solid state structure of the products varies from discrete complexes or clusters to a 3-dimensional coordination network. The mesityl group favors the formation of trinuclear units which are then linked in one, e.g. [Ag3(SMes)3(dpph)2] (5), two, e. g. [Ag3(SMes)3 (dpppt)2] (4), or three dimensions [Ag3(SMes)3(dppb)2] (3), via the phosphanes. With naphthyl and cyclohexyl groups mostly clusters are formed which are either isolated with some phosphanes in their ligand sphere, e.g. [Ag12(SCy)12(dpppt)2] (13), or additionally linked by the phosphanes to form 1-dimensional chains, e.g. [Ag12(SCy)12(dppo)] (17).

Protein–ligand interactions: Probing the energetics of a putative cation–π interaction

In order to probe the energetics associated with a putative cation–π interaction, thermodynamic parameters are determined for complex formation between the Grb2 SH2 domain and tripeptide derivatives of RCO–pTyr–Ac6c–Asn wherein the R group is varied to include different alkyl, cycloalkyl, and aryl groups. Although an indole ring is reputed to have the strongest interaction with a guanidinium ion, binding free energies, ΔG°, for derivatives of RCO–pTyr–Ac6c–Asn bearing cyclohexyl and phenyl groups were slightly more favorable than their indolyl analog. Crystallographic analysis of two complexes reveals that test ligands bind in similar poses with the notable exception of the relative orientation and proximity of the phenyl and indolyl rings relative to an arginine residue of the domain. These spatial orientations are consistent with those observed in other cation–π interactions, but there is no net energetic benefit to such an interaction in this biological system. Accordingly, although cation–π interactions are well documented as important noncovalent forces in molecular recognition, the energetics of such interactions may be mitigated by other nonbonded interactions and solvation effects in protein–ligand associations.