Ring Carbon Atoms Research Articles

Molecular insights into the aspartate protease Plasmepsin II activity inhibition by fluoroquinolones: A pathway to antimalarial drug development

Plasmepsin II (PlmII) belongs to the aspartate proteases and is involved in hemoglobin degradation in Plasmodium falciparum. Due to its critical role in the survival of the Plasmodium, PlmII is considered as a potent drug target for antimalarial therapy. We have done recombinant protein production of pro-plasmepsin II (Pro-plmII). Pro-PlmII was further activated to mature form (mPlmII) and its activity was confirmed by enzyme kinetics studies. The fluorescence spectroscopic and isothermal titration calorimetric studies show that fluoroquinolone-based antibiotic drugs norfloxacin, ciprofloxacin, and sparfloxacin bind with mPlmII. Molecular docking results show that only norfloxacin and ciprofloxacin are able to bind at the active site of mPlmII via hydrogen binding and hydrophobic interactions. Enzyme kinetics analysis reveals that norfloxacin and ciprofloxacin effectively inhibit mPlmII activity, while sparfloxacin does not exhibit any inhibitory effect on the enzyme's catalytic function. The two methyl groups on the 3rd and 5th carbon atoms of the piperazine ring make sparfloxacin unable to go inside mPlmII and bind at its active site. Overall, the results here suggested that fluoroquinolone-based antibiotic drugs norfloxacin, and ciprofloxacin, can be repurposed as antimalarial inhibitors targeting aspartic proteases. These findings contribute to pave the way for potential therapeutic interventions targeted at malaria.

Experimental and theoretical investigation of benzothiazole oxidation by OH in air and the role of O2.

Benzothiazole (BTH) and its derivatives are amongst a group of emerging contaminants that are widely distributed in the environment due to their extensive use in many different consumer products. In air, reaction with the hydroxyl radical (OH) is expected to be a major loss process for BTH in the gas phase, but the kinetics and mechanisms are unknown. Here, we report a combination of experiments and theory to determine both the rate constant and products of the reaction of OH with the smallest member of the series, benzothiazole, in the gas phase. The mechanism first involves an attack by OH on BTH to produce several OHBTH intermediates. This is followed by O2 reactions with OHBTH, leading to several stable products successfully predicted by theory. Relative rate studies at 1 atm in air and 298 K using benzene as a reference gave a rate constant for the BTH + OH reaction of 2.1 ± 0.1 × 10-12 (1σ) cm3 per molecule per s, which translates to a lifetime in air of 5.5 days at 1 × 106 OH cm-3. Four hydroxybenzothiazole products reflecting attack on different carbon atoms of the benzene ring were measured (n-OHBTH, where n = 4, 5, 6, 7), with the relative product yields well predicted by the calculated formation energies of the pre-reaction OH⋯BTH complex. Attack of OH on the -CH of the thiazole ring leads to the formation of 2-OHBTH, representing a smaller fraction of the overall reaction, and is shown to proceed through a more complex mechanism than attack on the benzene ring. A theoretical approach to predicting chromatographic retention times of the products based on solvation free energies (ΔGsolv) was successful for most of the products. These studies illustrate how the powerful combination of experiment and theory can be used to predict products of atmospheric oxidation of emerging contaminants and ultimately used to assess their impacts on the environment.

One- and two-step synthesis of paramylon mixed ester derivatives and the substitution effect on mechanical properties and seawater biodegradability

Paramylon acetate hexanoate (PaAcHex) with total DS=1.7 was prepared by one- and two-step methods with acetylation and hexanoylation in different order (denoted as AcHex and HexAc) in homogeneous DMAc/LiCl. The distribution of substitution at various ring carbon atoms (C2, C4, and C6) of PaAcHex synthesized by different methods was determined by 1H NMR spectroscopic analysis. The AcHex mixed esters showed a higher DS of long-chain Hex on C2 and C4 than the other samples. All mixed esters were amorphous and their glass transition temperatures (Tg) were obtained from DMA measurements. PaAcHex with higher DS of hexanoate groups had lower Tg and their melt films showed higher flexibility at the same total DS for all three series of samples. PaAcHex films produced by the two-step (AcHex) method exhibited high toughness even with a low DS of hexanoate groups, whereas those synthesized by the one-step and two-step (HexAc) methods were weak and brittle. Biochemical oxygen demand tests indicated that the mixed esters prepared by the two-step (AcHex) method underwent a two-step degradation process, which may be related to the hexanoate groups on C2 and C4. Short–long chain acylation by the two-step (AcHex) method was found to be the optimal synthesis technique for polysaccharide esters that displayed favorable thermoplasticity and controllable seawater biodegradation behavior. These polysaccharide esters show promise as bioplastic materials.

A Dynamic Loop in Halohydrin Dehalogenase HheG Regulates Activity and Enantioselectivity in Epoxide Ring Opening.

Halohydrin dehalogenase HheG and its homologues are remarkable enzymes for the efficient ring opening of sterically demanding internal epoxides using a variety of nucleophiles. The enantioselectivity of the respective wild-type enzymes, however, is usually insufficient for application and frequently requires improvement by protein engineering. We herein demonstrate that the highly flexible N-terminal loop of HheG, comprising residues 39 to 47, has a tremendous impact on the activity as well as enantioselectivity of this enzyme in the ring opening of structurally diverse epoxide substrates. Thus, highly active and enantioselective HheG variants could be accessed through targeted engineering of this loop. In this regard, variant M45F displayed almost 10-fold higher specific activity than wild type in the azidolysis of cyclohexene oxide, yielding the corresponding product (1S,2S)-2-azidocyclohexan-1-ol in 96%eeP (in comparison to 49%eeP for HheG wild type). Moreover, this variant was also improved regarding activity and enantioselectivity in the ring opening of cyclohexene oxide with other nucleophiles, demonstrating even inverted enantioselectivity with cyanide and cyanate. In contrast, a complete loop deletion yielded an inactive enzyme. Concomitant computational analyses of HheG M45F in comparison to wild type enzyme revealed that mutation M45F promotes the productive binding of cyclohexene oxide and azide in the active site by establishing noncovalent C-H ··π interactions between epoxide and F45. These interactions further position one of the two carbon atoms of the epoxide ring closer to the azide, resulting in higher enantioselectivity. Additionally, stable and enantioselective cross-linked enzyme crystals of HheG M45F were successfully generated after combination with mutation D114C. Overall, our study highlights that a highly flexible loop in HheG governs the enzyme's activity and selectivity in epoxide ring opening and should thus be considered in future protein engineering campaigns of HheG.

Insight into the Reversible Hydrogen Storage of Titanium-Decorated Boron-Doped C20 Fullerene: A Theoretical Prediction

Hydrogen storage has been a bottleneck factor for the application of hydrogen energy. Hydrogen storage capacity for titanium-decorated boron-doped C20 fullerenes has been investigated using the density functional theory. Different boron-doped C20 fullerene absorbents are examined to avoid titanium atom clustering. According to our research, with three carbon atoms in the pentagonal ring replaced by boron atoms, the binding interaction between the Ti atom and C20 fullerene is stronger than the cohesive energy of titanium. The calculated results revealed that one Ti atom can reversibly adsorb four H2 molecules with an average adsorption energy of −1.52 eV and an average desorption temperature of 522.5 K. The stability of the best absorbent structure with a gravimetric density of 4.68 wt% has been confirmed by ab initio molecular dynamics simulations. These findings suggest that titanium-decorated boron-doped C20 fullerenes could be considered as a potential candidate for hydrogen storage devices.

A 1,3,5-triazine μ3-bridged neutral Cu(I) framework with enhanced stability and CO2 capture selectivity

Compounds with 1,3,5-triazine ring such as melamine derivatives, known for their low cost and high stability, offer potential for affordable, stable metal organic framework (MOF) synthesis. However, reported such frameworks are facing issues like low stability and reduced porosity. To overcome such problems, we explored organic ligands with protonated nitrogen atoms on the 1,3,5-triazine ring, facilitated by introducing hydroxyl groups on carbon atoms of the triazine ring to construct MOFs. By using 5-azacytosine, we have successfully synthesized SXU-121, a neutral ultramicroporous MOF with eta-topology and high density of open Cu(I) sites. SXU-121 features robust structural stability and significant CO2 adsorption capacity with high selectivity over N2 under ambient conditions. We believe SXU-121's development opens new avenues for creating a class of stable and low cost metal-triazine frameworks with potential diverse functionalities.

Cheminformatics approaches to predict the bioactivity and to discover the pharmacophoric traits crucial to block NF-κB

Many human disorders include NF-kB signaling pathways, making IKK a therapeutic target in cancer treatment. Inflammatory illnesses and cancer are examples. COVID-19 is one of several triggers that stimulate NF-kB signaling. The activation of the NF-kB pathway is necessary for COVID-19 to cease its development. To learn more about the mechanism and structural features essential to IKK inhibition (IC50), molecular modeling studies have been undertaken on experimentally reported 503. QSAR analysis explores certain reported and hidden structural features critical for IKKβ inhibition. The OECD guidelines guided the construction of the QSAR model, which achieved all the endorsed threshold values for all validation parameters (R2tr:0.81, R2LMO:0.80, and R2ext:0.78). The present QSAR study shows that IKK inhibitory activity is linked to the following structural features: lipophilic hydrogen atoms within 2 A units of the molecule's center of mass; ring nitrogen atoms within one bond of planar nitrogen atoms; ring carbon atoms exactly four bonds from the non-ring nitrogen atoms; planar nitrogen atoms exactly four bonds from sp2 hybridized carbon atoms; and so on. Pharmacophore modeling highlighted QSAR-identified structural characteristics. To investigate binding, we docked all 503 molecules. The observation indicates that the QSAR and molecular docking/pharmacophore modeling findings are in agreement. Following this, we conducted 200 ns of molecular dynamics simulation to validate the molecular docking protocol. MMGBSA analysis determined the binding energy of the dock complex. Thus, the current study found unique pharmacophoric properties that may assist in optimizing lead/hit compounds for anti-IKKβ activity.

Catalytic Activity of an Asymmetric Uranyl‐Salophen on 2,4‐Dichlorophenol, 2,4,6‐Trichlorophenol, and Pentachlorophenol

ABSTRACTThis study employs density functional theory to investigate whether asymmetric uranyl‐Salophen catalyzes the activation of 2,4‐dichlorophenol, 2,4,6‐trichlorophenol, and pentachlorophenol. Changes in various important parameters such as bond lengths, Wiberg bond indices, infrared vibrational absorption spectra, natural charge distributions, ultraviolet–visible absorption spectra, and 13C NMR chemical shifts of the aromatic rings of chlorophenols before and after forming complexes with asymmetric uranyl‐Salophen are analyzed. This means that asymmetric uranyl‐Salophen indeed activates 2,4‐dichlorophenol, 2,4, 6‐trichlorophenol, and pentachlorophenol, significantly lengthening the aromatic ring bonds of the three chlorophenols and increasing the electrophilicity of the carbon atoms in the aromatic ring. This suggests that the conjugated system of the aromatic ring is also partially disrupted, indicating that these three chlorophenols are indeed catalytically activated. Furthermore, this implies that this asymmetric uranyl‐Salophen may be used to degrade chlorophenols in water.

Caging Bioactive Triarylimidazoles: An Approach to Create Visible Light-Activatable Drugs.

Imidazoles are crucial structural components in a variety of small-molecule inhibitors designed to target different kinases in anticancer treatment. However, the effectiveness of such inhibitors is often hampered by nonspecific effects and the development of resistance. Photopharmacology provides a compelling solution by enabling external control over drug activity with spatiotemporal precision. Herein, we introduce a novel strategy for caging bioactive triarylimidazole-based drug molecules. This approach involves introducing a dialkylamino group as a photoremovable group on the carbon atom of the imidazole ring, which intrinsically modulates the core structure from planar imidazole to tetrahedral 2H-imidazole, enabling the caged compound to be selectively uncaged upon visible light exposure. We applied this innovative caging technique to SB431542, a triarylimidazole-based small-molecule inhibitor that targets the pivotal TGF-β signaling pathway, the dysregulation of which is linked to several human diseases, including cancer. Our results demonstrated the selective inhibition of human breast cancer cell migration in vitro upon light activation, highlighting the potential of our approach to transform triarylimidazole-based drug molecules into visible light-activatable drugs, thereby facilitating spatiotemporal regulation of their pharmacological activity.

Synthesis and crystal structures of three organoplatinum(II) complexes bearing natural arylolefin and quinoline derivatives

Three organoplatinum(II) complexes bearing natural arylolefin and quinoline derivatives, namely, [4-methoxy-5-(2-methoxy-2-oxoethoxy)-2-(prop-2-en-1-yl)phenyl](quinolin-8-olato)platinum(II), [Pt(C13H15O4)(C9H6NO)], (I), [4-methoxy-5-(2-oxo-2-propoxyethoxy)-2-(prop-2-en-1-yl)phenyl](quinoline-2-carboxylato)platinum(II), [Pt(C15H19O4)(C10H6NO2)], (II), and chlorido[4-methoxy-5-(2-oxo-2-propoxyethoxy)-2-(prop-2-en-1-yl)phenyl](quinoline)platinum(II), [Pt(C15H19O4)Cl(C9H7N)], (III), were synthesized and structurally characterized by IR and 1H NMR spectroscopy, and by single-crystal X-ray diffraction. The results showed that the cycloplatinated arylolefin coordinates with PtII via the carbon atom of the phenyl ring and the C=Colefinic group. The deprotonated 8-hydroxyquinoline (C9H6NO) and quinoline-2-carboxylic acid (C10H6NO2) coordinate with the PtII atom via the N and O atoms in complexes (I) and (II) while the quinoline (C9H7N) coordinates via the N atom in (III). Moreover, the coordinating N atom in complexes (I)–(III) is in the cis position compared to the C=Colefinic group. The crystal packing is characterized by C—H...π, C—H...O [for (II) and (III)], C—H...Cl [for (III) and π–π [for (I)] interactions.

Mechanistic Insights into the Excited-State Intramolecular Proton Transfer (ESIPT) Process of 2-(2-Aminophenyl)naphthalene.

The 2-(2-aminophenyl)naphthalene molecule attracted much attention due to excited-state intramolecular proton transfer (ESIPT) from an amino NH2 group to a carbon atom of an adjacent aromatic ring. The ESIPT mechanisms of 2-(2-aminophenyl)naphthalene are still unclear. Herein, the decay pathways of this molecule in vacuum were investigated by combining static electronic structure calculations and nonadiabatic dynamics simulations. The calculations indicated the existence of two stable structures (S0-1 and S0-2) in the S0 and S1 states. For the S0-1 isomer, upon excitation to the Franck-Condon point, the system relaxed to the S1 minimum quickly, and then there exist four decay pathways (two ESIPT ones and two decay channels with C atom pyramidalization). In the ESIPT decay pathways, the system encounters the S1S0-PT-1 or S1S0-PT-2 conical intersection, which funnels the system rapidly to the S0 state. In the other two pathways, the system de-excited from the S1 to the S0 state via the S1S0-1 or S1S0-2 conical intersection. For the S0-2 structure, the decay pathways were similar to those of S0-1. The dynamics simulations showed that 75 and 69% of trajectories experienced the two ESIPT conical intersections for the S0-1 and S0-2 structures, respectively. Our simulations showed that the lifetime of the S1 state of S0-1 (S0-2) is estimated to be 358 (400) fs. Notably, we not only found the detailed reaction mechanism of the system but also found that the different ground-state configurations of this system have little effect on the reaction mechanism in vacuum.

Crystal structure and Hirshfeld surface analysis of dimethyl 4'-bromo-3-oxo-5-(thio-phen-2-yl)-3,4,5,6-tetra-hydro-[1,1'-biphen-yl]-2,4-di-carboxyl-ate.

In the title compound, C20H17BrO5S, mol-ecules are connected by inter-molecular C-H⋯S hydrogen bonds with R 2 2(10) ring motifs, forming ribbons along the b-axis direction. C-H⋯π inter-actions consolidate the ribbon structure while van der Waals forces between the ribbons ensure the cohesion of the crystal structure. According to a Hirshfeld surface analysis, H⋯H (40.5%), O⋯H/H⋯O (27.0%), C⋯H/H⋯C (13.9%) and Br⋯H/H⋯Br (11.7%) inter-actions are the most significant contributors to the crystal packing. The thio-phene ring and its adjacent di-carboxyl-ate group and the three adjacent carbon atoms of the central hexene ring to which they are attached were refined as disordered over two sets of sites having occupancies of 0.8378 (15) and 0.1622 (15). The thio-phene group is disordered by a rotation of 180° around one bond.

Gas-Phase Reactivity of Quinoline-Based Singlet Oxenium Cations.

Isomeric quinolyloxenium cations were generated in the gas phase in an ion trap mass spectrometer to explore their reactions. The structures of some products were identified via collision-activated dissociation experiments involving model compounds to demonstrate that they have the expected heavy atom connectivity. The lack of radical reactions suggests that the cations have closed-shell singlet electronic ground states. Calculations (CASPT2/CASSCF(16,14)/cc-pVTZ//CASSCF(16,14)/cc-pVTZ) predict that their closed-shell singlet (1A') ground states are lower in energy by ca. 25 kcal mol-1 than their lowest-lying excited states. All cations are reactive toward dimethyl disulfide, dimethyl sulfide, and allyl iodide and most toward water and moderately reactive toward cyclohexane, reflecting their strongly electrophilic nature. They form adducts with nucleophiles in exothermic reactions (ca. 50 kcal mol-1 for dimethyl sulfide) that can fragment or be stabilized via IR emission. Most water adducts spontaneously isomerize to lower-energy tautomers. The nucleophiles preferentially add to those carbon atoms in the benzene ring that have the greatest positive charge (but not the carbonyl carbon). The cations react with cyclohexane via hydride abstraction by the oxygen atom. This is the only reaction that initially involves the oxygen atom and hence reflects the formally positively charged, monovalent oxygen atom in these cations.

Review of: "C70 Fullerenes Closed hollow cages are made of interconnected carbon atoms in pentagonal and hexagonal rings with a cage-like melted ring structure that resembles a rugby ball"

Review of: "C70 Fullerenes Closed hollow cages are made of interconnected carbon atoms in pentagonal and hexagonal rings with a cage-like melted ring structure that resembles a rugby ball"

Review of: "C70 Fullerenes Closed hollow cages are made of interconnected carbon atoms in pentagonal and hexagonal rings with a cage-like melted ring structure that resembles a rugby ball"

Review of: "C70 Fullerenes Closed hollow cages are made of interconnected carbon atoms in pentagonal and hexagonal rings with a cage-like melted ring structure that resembles a rugby ball"

Charging modulation of the pyridine nitrogen of covalent organic frameworks for promoting oxygen reduction reaction

Covalent organic frameworks (COFs) are ideal templates for constructing metal-free catalysts for the oxygen reduction reaction due to their highly tuneable skeletons and controllable porous channels. However, the development of highly active sites within COFs remains challenging due to their limited electron-transfer capabilities and weak binding affinities for reaction intermediates. Herein, we constructed highly active catalytic centres by modulating the electronic states of the pyridine nitrogen atoms incorporated into the frameworks of COFs. By incorporating different pyridine units (such as pyridine, ionic pyridine, and ionic imidazole units), we tuned various properties including dipole moments, reductive ability, hydrophilicity, and binding affinities towards reaction intermediates. Notably, the ionic imidazole COF (im-PY-BPY-COF) exhibited greater activity than the neutral COF (PY-BPY-COF) and ionic pyridine COF (ion-PY-BPY-COF). Specifically, im-PY-BPY-COF demonstrated a half-wave potential of 0.80 V in 0.1 M KOH, outperforming other metal-free COFs. Theoretical calculations and in situ synchrotron radiation Fourier transform infrared spectroscopy confirmed that the carbon atoms in the ionic imidazole rings improved the activity by facilitating binding of the intermediate OOH* and promoting the desorption of OH*. This study provides new insights into the design of highly active metal-like COF catalysts.

Mid-IR and CH stretching vibrational circular dichroism spectroscopy to distinguish various sources of chirality: The case of quinophaneoxazoline based ruthenium(II) complexes.

Five diastereomers of ruthenium(II) complexes based on quinolinophaneoxazoline ligands were investigated by vibrational circular dichroism (VCD) in the mid-IR and CH stretching regions. Diastereomers differ in three sources of chirality: the planar chirality of the quinolinophane moiety, the central chirality of an asymmetric carbon atom of the oxazoline ring, and the chirality of the ruthenium atom. VCD, allied to DFT calculations, has been found to be effective in disentangling the various forms of chirality. In particular, a VCD band is identified in the CH stretching region directly connected to the chirality of the metal. The analysis of the calculated VCD spectra is carried out by partitioning the complexes into fragments. The anharmonic analysis is also performed with a recently proposed reduced-dimensionality approach: such treatment is particularly important when examining spectroscopic regions highly perturbed by resonances, like the CH stretching region.

QSAR modelling to predict structural features of certain sulfonamide as Urokinase-type Plasminogen Activator inhibitors

The serine hydrolase family includes serine proteases. It is essential for hydrolyzing protein peptide bonds and breaking them. The urokinase-type plasminogen activator (uPA) selectively binds to the uPAR on numerous cell types, including cancer cells. Pericellular proteolysis of cell-bound proteins requires this interaction. High uPA and uPAR levels regularly worsen cancer prognoses. Thus, small chemical active-site inhibitors that block uPA may diminish cancer cell invasion and metastasis. In compliance with Organization for Economic Corporation and Development guidelines, this research performed a complete Quantitative structure activity relationship analysis of sulfonamide compounds as Urokinase-type Plasminogen Activator inhibitors. Py-Descriptors were used for this investigation. PyDescriptor uses PyMOL standards and idioms to calculate 11,145 simple molecular descriptors. This plugin calculates molecular descriptors irrespective of molecular representation properties like atom numbering or labelling, spatial reference frame, translational and rotational invariance, etc. The investigation sought to find essential and hidden structural characteristics that regulate sulfonamide-type drugs' Urokinase-type Plasminogen Activator Inhibitory action. Twenty-eight sulfonamide chemicals are used in the Quantitative structure activity relationship study to generate statistically robust and highly predictive univariate and multivariate models. All models were thoroughly evaluated and meet several statistical parameter thresholds (e.g., R2 =0.9259–0.9280, Q2Loo= 0.8579–0.8558, Q2LMO= 0.8013–0.7865). The analysis reveal that occurance of ring carbon atoms exactly at 3 A0 from carbon atom, number of negatively charged atoms from sulphur atoms within 5 bonds, presence of hydrogen atom exactly at 3 bonds from donar atoms, presence of carbon atom exactly at 4 A0 from donar atom, presence of acceptor atom exactly at 5 A0 from sulphur atom and sum of partial charges of lipo atoms within 6 bonds from sulphur atom are important pharmacophoric features for Urokinase-type Plasminogen Activator Inhibition binding affinity. Thus, the developed Quantitative structure activity relationship study has an equilibrium of quantitative and qualitative tactics. The results could be useful for future optimizations of sulfonamide analogues.

Expected values of sum-based topological indices of random cyclodecane chains

Cyclodecanes, belonging to the class of aliphatic cycloalkanes, comprise non-aromatic carbon-atom rings. Within the 10-membered ring, cyclodecanes exhibit various isomers, characterized by different spatial arrangements of carbon atoms. Serving as model compounds in organic studies, cyclodecanes offer insights into the properties and reactivity of cyclic hydrocarbons. The chemistry of cyclodecane serves as a valuable foundation for understanding the behavior of more complex hydrocarbons. In this paper, we explore the potential probabilities of random cyclodecane chains Dtρ of length t ≥ 3. We derive exact expressions for the expected values of the modified second Zagreb index, inverse index, and second NDe index. A theoretical comparative analysis of these descriptors is provided, accompanied by graphical and numerical representations of the obtained results.

Syntheses, characterizations, crystal structures and Hirshfeld surface analyses of methyl 4-[4-(di-fluorometh-oxy)phen-yl]-2,7,7-trimethyl-5-oxo-1,4,5,6,7,8-hexa-hydro-quinoline-3-carboxyl-ate, isopropyl 4-[4-(di-fluoro-meth-oxy)phen-yl]-2,6,6-trimethyl-5-oxo-1,4,5,6,7,8-hexa-hydro-quinoline-3-carboxyl-ate and tert-butyl 4-[4-(di-fluoro-meth-oxy)phen-yl]-2,6,6-trimethyl-5-oxo-1,4,5,6,7,8-hexa-hydro-quinoline-3-carboxyl-ate.

The crystal structures and Hirshfeld surface analyses of three similar compounds are reported. Methyl 4-[4-(di-fluoro-meth-oxy)phen-yl]-2,7,7-trimethyl-5-oxo-1,4,5,6,7,8-hexa-hydro-quinoline-3-carboxyl-ate, (C21H23F2NO4), (I), crystallizes in the monoclinic space group C2/c with Z = 8, while isopropyl 4-[4-(di-fluoro-meth-oxy)phen-yl]-2,6,6-trimethyl-5-oxo-1,4,5,6,7,8-hexa-hydro-quinoline-3-carb-oxyl-ate, (C23H27F2NO4), (II) and tert-butyl 4-[4-(di-fluoro-meth-oxy)phen-yl]-2,6,6-trimethyl-5-oxo-1,4,5,6,7,8-hexa-hydro-quinoline-3-carboxyl-ate, (C24H29F2NO4), (III) crystallize in the ortho-rhom-bic space group Pbca with Z = 8. In the crystal structure of (I), mol-ecules are linked by N-H⋯O and C-H⋯O inter-actions, forming a tri-periodic network, while mol-ecules of (II) and (III) are linked by N-H⋯O, C-H⋯F and C-H⋯π inter-actions, forming layers parallel to (002). The cohesion of the mol-ecular packing is ensured by van der Waals forces between these layers. In (I), the atoms of the 4-di-fluoro-meth-oxy-phenyl group are disordered over two sets of sites in a 0.647 (3): 0.353 (3) ratio. In (III), the atoms of the dimethyl group attached to the cyclo-hexane ring, and the two carbon atoms of the cyclo-hexane ring are disordered over two sets of sites in a 0.646 (3):0.354 (3) ratio.