Methyl Moiety Research Articles

An Investigation of RNA Methylations with Biophysical Approaches in a Cervical Cancer Cell Model

RNA methylation adds a second layer of genetic information that dictates the post-transcriptional fate of RNAs. Although various methods exist that enable the analysis of RNA methylation in a site-specific or transcriptome-wide manner, whether biophysical approaches can be employed to such analyses is unexplored. In this study, Fourier-transform infrared (FT-IR) and circular dichroism (CD) spectroscopy are employed to examine the methylation status of both synthetic and cellular RNAs. The results show that FT-IR spectroscopy is perfectly capable of quantitatively distinguishing synthetic m6A-methylated RNAs from un-methylated ones. Subsequently, FT-IR spectroscopy is successfully employed to assess the changes in the extent of total RNA methylation upon the knockdown of the m6A writer, METTL3, in HeLa cells. In addition, the same approach is shown to accurately detect reduction in total RNA methylation upon the treatment of HeLa cells with tumor necrosis factor alpha (TNF-α). It is also demonstrated that m1A and m6A methylation induce quite a distinct secondary structure on RNAs, as evident from CD spectra. These results strongly suggest that both FT-IR and CD spectroscopy methods can be exploited to uncover biophysical properties impinged on RNAs by methyl moieties, providing a fast, convenient and cheap alternative to the existing methods.

Human phase-I metabolism of three synthetic cannabinoids bearing a cumyl moiety and a cyclobutyl methyl or norbornyl methyl tail: Cumyl-CBMEGACLONE, Cumyl-NBMEGACLONE, and Cumyl-NBMINACA.

Synthetic cannabinoid receptor agonists (SCRAs) continue to show high prevalence on the new psychoactive substances drug market. Around 2019-2020, new SCRAs bearing a cumyl moiety emerged: Cumyl-CBMEGACLONE and Cumyl-NBMEGACLONE, carrying a cyclobutyl methyl (CBM) and a norbornyl methyl moiety (NBM) attached to the γ-carbolinone core. These were followed by Cumyl-NBMINACA, the indazole carboxamide analog of Cumyl-NBMEGACLONE. The study aimed at evaluating the human phase-I metabolism of these compounds and at identifying suitable urinary markers to prove their consumption. After enzymatic hydrolysis, 14 authentic urine samples (eight for Cumyl-CBMEGACLONE, four for Cumyl-NBMEGACLONE, and two for Cumyl-NBMINACA) were analyzed by liquid chromatography-quadrupole time-of-flight mass spectrometry. Results were compared with in vitro metabolites generated by pooled human liver microsomes incubation. Fifteen human phase-I metabolites were identified for Cumyl-CBMEGACLONE, nine for Cumyl-NBMEGACLONE, and thirteen for Cumyl-NBMINACA. The main in vivo metabolites were built by monohydroxylation, dihydroxylation, or trihydroxylation. The following urinary biomarkers are suggested for detecting the consumption of the investigated SCRAs: products of monohydroxylation at the CBM and at the core for Cumyl-CBMEGACLONE; two products of monohydroxylation at the norbonyl methyl tail for Cumyl-NBMEGACLONE; and metabolites built by dihydroxylation at the NBM substructure and by an additional hydroxylation at the cumyl moiety for Cumyl-NBMINACA.

Endolysin CHAP domain-carbosilane metallodendrimer complexes with triple action on Gram-negative bacteria: Membrane destabilization, reactive oxygen species production and peptidoglycan degradation

Bacterial resistance to antibiotics is a significant challenge that is associated with increased morbidity and mortality. Gram-negative bacteria are particularly problematic due to an outer membrane (OM). Current alternatives to antibiotics include antimicrobial peptides or proteins and multifunctional systems such as dendrimers. Antimicrobial proteins such as lysins can degrade the bacterial cell wall, whereas dendrimers can permeabilize the OM, enhancing the activity of endolysins against gram-negative bacteria. In this study, we present a three-stage action of endolysin combined with two different carbosilane (CBS) silver metallodendrimers, in which the periphery is modified with N-heterocyclic carbene (NHC) ligands coordinating a silver atom. The different NHC ligands contained hydrophobic methyl or N-donor pyridyl moieties. The effects of these endolysin/dendrimer combinations are based on OM permeabilization, peptidoglycan degradation, and reactive oxygen species production. The results showed that CBS possess a permeabilization effect (first action), significantly reduced bacterial growth at higher concentrations alone and in the presence of endolysin, increased ROS production (second action), and led to bacterial cell damage (third action). The complex formed between the CHAP domain of endolysin and a CBS silver metallodendrimer, with a triple mechanism of action, may represent an excellent alternative to other antimicrobials with only one resistance mechanism.

Hydrogen bonding to the electron accepting group controls the absorption spectrum of a push–pull stilbene adsorbed on amorphous silica

The photophysical and photochemical properties of push–pull photoswitches, such as stilbene derivatives, are very sensitive to their surroundings, allowing, e.g., for the control of the spectral properties or alternatively for probing the molecular environment. Here, we investigate how various adsorption motifs of 4-(N, N-Dimethylamino)-4’-nitrostilbene (DANS) on an amorphous glass surface influence its absorption spectra. Particular attention is given to the prominent first bright charge transfer state and the factors governing these modifications. The absorption spectra is simulated using time-dependent density functional theory on a large set of adsorption geometries that exhibit different kinds of molecule–surface interactions. We find that C–H⋯O interactions of the methyl or phenyl moieties with the glass affect the spectrum only marginally, whereas the dispersion interaction of the π system with the surface tends to diminish the intensity of the first absorption band. Moreover, an enhancement of the push–pull properties of DANS and a significant redshift occur whenever O–H⋯O hydrogen bonds with the NO2 group are present, whereas a hydrogen bond O–H⋯N to the NMe2 group results in a blueshift.

Synthesis and In vitro evaluation of bichalcones as novel anti-toxoplasma agents.

Toxoplasmosis is a zoonotic disease caused by Toxoplasma gondii, an apicomplexan parasite that infects approximately a third of the world's human population. This disease can cause serious complications during pregnancy and can be fatal in immunocompromised hosts. The current treatment options for toxoplasmosis face several limitations. Thus, to address the urgent medical need for the discovery of novel anti-toxoplasma potential drug candidates, our research focused on exploring a series of monomeric and dimeric chalcones, polyphenolic molecules belonging to the class of flavonoids. Chalcones 1aa-1bg and axially chiral A-A'-connected bichalcones 2aa-2bg were evaluated in vitro against the proliferation of the parasite in a cell-based assay. A comparison of the efficacy demonstrated that, in several cases, bichalcones exhibited increased bioactivity compared to their corresponding monomeric counterparts. Among these compounds, a bichalcone with a phenyl substituent and a methyl moiety 2ab showed the most potent and selective inhibitory activity in the nanomolar range. Both enantiomers of this bichalcone were synthesized using an axially chiral biphenol building block. The biaryl bond was forged using Suzuki cross-coupling in water under micellar catalysis conditions. Separation of the atropisomers of this biphenol building block was conducted by chiral HPLC on a preparative scale. The biological evaluation of the enantiomers revealed that the (R a)-enantiomer (R a)-2ab is the eutomer. These studies suggest that bichalcones may be important drug candidates for further in vivo evaluations for the discovery of anti-toxoplasma drugs.

Methyl and Benzyl (Ethyl 3,4-di-O-benzyl-2-O-benzoyl-1-thio-β-d-glucopyranosyl)uronate

Methyl and benzyl (ethyl 3,4-di-O-benzyl-2-O-benzoyl-1-thio-β-D-glucopyranosyl)uronate were synthesised from a protected thioglycoside in three steps. A regioselective ring opening of the benzylidene acetal with BH3.THF generated C6-OH material, which was subsequently oxidised using biphasic TEMPO/BAIB conditions. The resultant uronic acid was esterified with either a methyl or benzyl moiety. The products were obtained on a multigram scale and fully characterised by 1H, 13C and 2D NMR, alongside MS and IR analysis.

Synthesis of four-ring unsymmetrical bent-core mesogens and cybotactic cluster formation in their nematic phase

The synthesis and characterization of novel achiral unsymmetrical four-ring bent-core molecules resembling a hockey-stick shape are described. The present compounds bearing a methyl substituent in the central phenyl ring exhibit the skewed cybotactic nematic (NcybC), smectic C (SmC) and additional tilted smectic phase with tilted molecular arrangement. The skewed cybotactic nematic phase is formed by the bent-core molecules with long range orientational ordered clusters possessing local smectic C type order and within a cluster of tilted molecular assembly. The previously reported four-ring compounds without the methyl moiety did not exhibit nematic phase but show polarization modulated B1revtilt phase. The x-ray diffraction pattern clearly indicated the existence of SmC-type cybotactic clusters over a wide N temperature range; the layer reflection peak is weak at a higher temperature region and becomes more conspicuous with decreasing temperature. The lower temperature phase is distinctly the SmC phase, and in addition another tilted smectic phase emerges below SmC.

Photostability evaluation of manidipine tablets and structural determination of its photoproducts.

Manidipine (MP) is a dihydropyridine drug, which is treated for the reduction of high blood pressure. The aim of this study is to clarify the photochemical behavior of MP in the case of ultraviolet light (UV) irradiation for MP tablets (Calslot® tablets). The tablets and its altered forms (powders and suspensions) were UV-irradiated using a black light, and residual amounts of active pharmaceutical ingredients (APIs) were monitored by high-performance liquid chromatography (HPLC). Due to the photoproducts of MP were detected in HPLC chromatograms, the elucidation of their chemical structures was carried out utilizing electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS). As a result, APIs in Calslot® tablets were almost completely photodegraded in the case that Calslot® tablets were suspended in an aqueous media along with the generation of some MP photoproducts. LC-ESI-MS/MS analysis clarified the chemical structures of three MP photoproducts, indicating that they were a pyridine analogue, benzophenone and a hydrolysate. Benzophenone was a main MP photoproduct. It was possible that MP might be firstly oxidized to form its pyridine analogue, followed by the oxidation of a dimethyl methylene moiety. This moiety seemed to be eliminated as a benzophenone, and the cleavage of an ester bond of the residual moiety resulted in the generation of a hydrolysate. Finally, toxicological potencies of MP and its photoproducts were predicted in silico toxicity evaluation, suggesting some of biological effects of the photoproducts might be altered compared with MP.

Structure based design, synthesis of novel fused triazole-thiazole derivatives and their comparative study on Alzheimer disease along with in silico modeling

In this approach, fused triazole thiazole derivatives (1–14) were synthesized and designed as dual inhibitors of AChE and BuChE which exhibit promising inhibitory activity to cure one of the progressive disorders, Alzheimer’s disease. Different spectroscopic techniques (13C NMR, 1H NMR and HREI-MS) were employed for the synthetic confirmations of all the derivatives. Using the standard drug donepezil (IC50 = 10.60 ± 0.20 for AChE and 11.80 ± 0.49 µM for BuChE). All the analogues in the current series showed a wide range of inhibitory potentials such as (IC50 = 7.20 ± 0.10 to 17.50 ± 0.10 µM for AChE and IC50 = 8.10 ± 0.20 to 18.20 ± 0.10 µM for BuChE). The nature, number and position of the attached substituents in the phenyl ring greatly influenced the inhibitory activity of the current analogues in the series. However, Analogue 4 with IC50 values (7.20 ± 0.10, 8.10 ± 0.20 µM) showed immense potency due to para substituted tri-fluoro methyl moiety. Molecular docking studies and ADME analysis was also conducted for the excellent binding interactions with target enzymes and drug like properties of the potent analogues.

Synthesis, XRD/HSA-interactions, synthon, TD-DFT/optical analysis, docking and antibacterial evaluation of two (±)-Isoflavonoid derivatives

A high-yield synthesis of the new racemic (±)-2-(1-bromoethyl)-7‑methoxy-3-(4-methoxyphenyl)-4H-chromen-4-one was achieved in two steps by O- and 2-C-methylation 7,4′-dihydroxy-2-methylisoflavone, followed by radical bromination of the allylic methylene moiety using N-bromosuccinimide. XRD-crystallography, NMR, UV–vis CHN-EA, and FT-IR were all used to establish the identity and structure of the target ligand. Both the XRD, Hirshfeld surface area (HSA) and the DFT structural optimization validated the (±)‑bromo-chromen-4-one structural formula. XRD analysis reveals two types of synthons due to the presence of multiple short interactions, including CMe-H.....Br/Cph-H.....O and H…πCC. There is a high harmony between the experimental XRD-structural parameters and their DFT counterparts; additionally, the optical characteristics were derived by comparing the experimental UV–Vis result to the TD-DFT/B3LYP and TD-DFT/CAM-B3LYP ones. The compounds capacity to bind to DNA was assessed via the molecular docking technique with the use of 1BNA. The antibacterial activity of the produced (±)‑bromo-chroman-4-one and (±)-the non bromo‑chroman-4-one derivatives was evaluated against eight bacterial strains.

Photocatalytic, α-Aminoalkyl Radical-Mediated, Methylene-Extrusive Ring-Closing Transformation of o-Alkynyl and o-Cyano Acrylamides.

Herein we report a visible-light-induced, α-aminoalkyl radical-mediated cascade reaction of 1,7-enynes that establishes a unique ring-closing enyne transformation pathway which occurs with concomitant loss of a methylene moiety. The α-aminoalkyl radical derived from N,N-dimethylaniline was demonstrated to be a traceless promoter of enyne reorganization leading to 4-alkylquinolinones. The reaction can also be extended to nitrile-substituted acrylamide systems, leading to carbostyrils. Experiments with deuterated N,N-dimethylaniline-d6 (PhN(CD3)2) established the involvement of 1,5-H atom transfer in the mechanism.

Modulation of [CuOH/O]+ Properties in [2,2'-Bipyridine]2 Homoleptic Complexes through Substitution at the 6,6' Position by Methyl Groups.

In this paper, data from a DFT-based computational study on the reactivity of [Cu(2,2'-S-bpy)2]+PF6- (S indicating substitution by methyl groups at the 6 and/or 6' position and ranging from 0 to 100% through 50%) homoleptic complexes based toward tButOOH were presented. Computational results, supported by cyclic voltammetry analysis, prove the feasibility of finely tuning the chemical properties of the complexes and their reactivity by means of insertion of methyl moieties in selected positions within the bipyridine scaffold.

Inhibition of Aflatoxin Production in Aspergillus flavus by a Klebsiella sp. and Its Metabolite Cyclo(l-Ala-Gly).

During an experiment where we were cultivating aflatoxigenic Aspergillus flavus on peanuts, we accidentally discovered that a bacterium adhering to the peanut strongly inhibited aflatoxin (AF) production by A. flavus. The bacterium, isolated and identified as Klebsiella aerogenes, was found to produce an AF production inhibitor. Cyclo(l-Ala-Gly), isolated from the bacterial culture supernatant, was the main active component. The aflatoxin production-inhibitory activity of cyclo(l-Ala-Gly) has not been reported. Cyclo(l-Ala-Gly) inhibited AF production in A. flavus without affecting its fungal growth in a liquid medium with stronger potency than cyclo(l-Ala-l-Pro). Cyclo(l-Ala-Gly) has the strongest AF production-inhibitory activity among known AF production-inhibitory diketopiperazines. Related compounds in which the methyl moiety in cyclo(l-Ala-Gly) is replaced by ethyl, propyl, or isopropyl have shown much stronger activity than cyclo(l-Ala-Gly). Cyclo(l-Ala-Gly) did not inhibit recombinant glutathione-S-transferase (GST) in A. flavus, unlike (l-Ala-l-Pro), which showed that the inhibition of GST was not responsible for the AF production-inhibition of cyclo(l-Ala-Gly). When A. flavus was cultured on peanuts dipped for a short period of time in a dilution series bacterial culture broth, AF production in the peanuts was strongly inhibited, even at a 1 × 104-fold dilution. This strong inhibitory activity suggests that the bacterium is a candidate for an effective biocontrol agent for AF control.

A further pocket or conformational plasticity by mapping COX-1 catalytic site through modified-mofezolac structure-inhibitory activity relationships and their antiplatelet behavior

Cyclooxygenase enzymes have distinct roles in cardiovascular, neurological, and neurodegenerative disease. They are differently expressed in different type of cancers. Specific and selective COXs inhibitors are needed to be used alone or in combo-therapies. Fully understand the differences at the catalytic site of the two cyclooxygenase (COX) isoforms is still opened to investigation. Thus, two series of novel compounds were designed and synthesized in fair to good yields using the highly selective COX-1 inhibitor mofezolac as the lead compound to explore a COX-1 zone formed by the polar residues Q192, S353, H90 and Y355, as well as hydrophobic amino acids I523, F518 and L352. According to the structure of the COX-1:mofezolac complex, hydrophobic amino acids appear to have free volume eventually accessible to the more sterically hindering groups than the methoxy linked to the phenyl groups of mofezolac, in particular the methoxyphenyl at C4-mofezolac isoxazole. Mofezolac bears two methoxyphenyl groups linked to C3 and C4 of the isoxazole core ring. Thus, in the novel compounds, one or both methoxy groups were replaced by the higher homologous ethoxy, normal and isopropyl, normal and tertiary butyl, and phenyl and benzyl. Furthermore, a major difference between the two sets of compounds is the presence of either a methyl or acetic moiety at the C5 of the isoxazole. Among the C5-methyl series, 12 (direct precursor of mofezolac) (COX-1 IC50 = 0.076 μM and COX-2 IC50 = 0.35 μM) and 15a (ethoxy replacing the two methoxy groups in 12; COX-1 IC50 = 0.23 μM and COX-2 IC50 > 50 μM) were still active and with a Selectivity Index (SI = COX-2 IC50/COX-1 IC50) = 5 and 217, respectively. The other symmetrically substituted alkoxyphenyl moietis were inactive at 50 μM final concentration. Among the asymmetrically substituted, only the 16a (methoxyphenyl on C3-isoxazole and ethoxyphenyl on C4-isoxazole) and 16b (methoxyphenyl on C3-isoxazole and n-propoxyphenyl on C4-isoxazole) were active with SI = 1087 and 38, respectively. Among the set of compounds with the acetic moiety, structurally more similar to mofezolac (SI = 6329), SI ranged between 1.4 and 943. It is noteworthy that 17b (n-propoxyphenyl on both C3- and C4-isoxazole) were found to be a COX-2 slightly selective inhibitor with SI = 0.072 (COX-1 IC50 > 50 μM and COX-2 IC50 = 3.6 μM). Platelet aggregation induced by arachidonic acid (AA) can be in vitro suppressed by the synthesized compounds, without affecting of the secondary hemostasia, confirming the biological effect provided by the selective inhibition of COX-1. A positive profile of hemocompatibility in relation to erythrocyte and platelet toxicity was observed. Additionally, these compounds exhibited a positive profile of hemocompatibility and reduced cytotoxicity. Quantitative structure activity relationship (QSAR) models and molecular modelling (Ligand and Structure based virtual screening procedures) provide key information on the physicochemical and pharmacokinetic properties of the COX-1 inhibitors as well as new insights into the mechanisms of inhibition that will be used to guide the development of more effective and selective compounds. X-ray analysis was used to confirm the chemical structure of 14 (MSA17).

Synthesis and reduction of [(C5H4SiMe3)2Ln(μ-OR)]2 (Ln = La, Ce) complexes: structural effects of bridging alkoxides.

Alcoholysis of Cp'3Ln (Ln = La, Ce; Cp' = C5H4SiMe3) generate high-yielding (72-97%) bimetallic LnIII complexes of [Cp'2Ln(μ-OR)]2 [R = Et, iPr, or C6H4-4-tBu]. Single-crystal X-ray diffraction of these complexes reveal unexpected decreases in Ln⋯Ln distances, increasing Cpcent-Ln-Cpcent angles, and increasing intermolecular C⋯C contacts with bulkier bridging alkoxides, in line with structural control driven by significant dispersion forces. 1H NMR spectroscopy of [Cp'2Ce(μ-OEt)]2 and [Cp'2Ce(μ-OiPr)]2 revealed significantly upfield resonances assigned as methylene and methine moieties of -43.74 and -70.85 ppm, respectively. 2D 1H DOSY NMR experiments of [Cp'2Ce(μ-OiPr)]2 in C6D6 supported a dimeric structure in solution, including in the presence of a Lewis base (i.e., THF). Reduction of [Cp'2La(μ-OiPr)]2 using KC8 in the presence of 2.2.2-cryptand at -78 °C generated a purple solution and X-band EPR spectroscopy revealed an eight-line hyperfine pattern indicative of a LaII species.

Determination of pKa of the methylene moiety of the Ni(II) complexed glycine Schiff base with N-(2-benzoyl-4-chlorophenyl)-2-dibutylamino-acetamide by spectroscopic methods in non-aqueous conditions

The C-H substitution of the methylene moiety of glycine in nickel(II) glycine Schiff bases has proven useful for the preparation of a variety of α-amino acids. Recently, it has been shown that the integration of electron withdrawing groups into the ligand system of these nickel(II) complexes enhances their reactivity. It is hypothesized that this enhanced reactivity is, in part, due to decreased pKa of the α-proton of glycine due to delocalization of the resulting charge. However, there is a lack information or direct evidence of the relationship between the pKa of the α-protons of glycine in these complexes and perturbation of the electronic system of the ligand in the literature. Therefore, to better understand the observed reactivity, a method to determine the pKa of these complexes in non-aqueous solvent conditions is needed. In this work, the method and data analysis to find the pKa of the Ni(II) complex of glycine Schiff base with N-(2-benzyoly-4-chlorophenyl)-2-dibutylamino-acetamide is described.

Three new flavones from the whole plants of Cassia auriculata Linn. and their antiviral activities

Cassia auriculata, a widely grown medicinal plant in China, has not been fully studied in terms of its secondary metabolites. In our pursuit of new bioactive metabolites from Cassia plants, we conducted a phytochemical reinvestigation on C. auriculata. This investigation resulted in the isolation of three new (1−3) and six known (4−9) flavones. Their structures were elucidated by spectroscopic methods, including extensive 1D- and 2D NMR techniques. Interestingly, Compounds 1-3 are rare flavones bearing an unusual (4-methylfuran-2-yl)methyl moiety. In addition, Compounds 1-3 were evaluated for their anti-tobacco mosaic virus (anti-TMV) activities. The results showed that Compounds 1–3 exhibited potential anti-TMV activities with inhibition rates of 26.8%, 30.5% and 34.6% at a concentration of 20 μM, respectively, and these rates are close to that of the positive control. Compounds 1-9 were also tested for their anti-rotavirus activities. The results revealed that 1–9 exhibited potential anti-rotavirus activity with therapeutic index (TI) values in the range of 13.3–20.8. These values are lower than that of the positive control (with a therapeutic index of 23.4).

Preparation and characterization of carboxymethylated Aureobasidium pullulans β-(1 → 3, 1 → 6)-glucan and its in vitro antioxidant activity

Aureobasidium pullulans β-(1 → 3, 1 → 6)-glucan (APG) has a high degree of β-(1 → 6)-glucosyl branching and a regular triple helical structure similar to that of schizophyllan. In this study, APG was carboxymethylated to different degrees of substitution (DS = 0.51, 1.0, and 2.0, denoted CMAPG 1–3, respectively) using a heterogeneous reaction. With increasing DS, the triple-helix structure drastically decreased and converted to a random coil structure in CMAPG 3. Further, aqueous solutions of CMAPG changed from pseudoplastic fluids to perfect Newtonian liquids with increasing DS, indicating that the intra- and intermolecular hydrogen bonds had been cleaved by the substituents to form a random coil structure. In addition, APG and CMAPG solutions exhibited scavenging ability against hydroxyl, organic, and sulfate radicals. It was also found that the carboxymethylation of APG drastically enhanced the organic radical scavenging ability. On the basis of the relationship between the DS and radical scavenging ability of the CMAPG samples, we believe hydroxyl and organic radicals were preferably scavenged by the donation of hydrogen atoms from the glucose rings and the methylene moieties of the carboxymethyl groups, respectively. Considering the obtained results, CMAPG and APG are expected to have applications in pharmaceuticals, functional foods, and cosmetics as antioxidant polysaccharides.

Why non-heme Mn complexes of amino 2-quinolylmethyl ligands are inactive in oxidation catalysis? An insight from X-ray data

In the last decade, manganese complexes with bis-amino-bis-pyridylmethyl and structurally related N4 donor ligands have emerged as efficient catalysts of selective epoxidations and C–H oxidations of organic substrates with H2O2. Although a plethora of various ligand structures have been designed, (quinolin-2-yl)methyl moieties have not been involved in constructing such catalysts. Herewith we report crystal structures of several Mn complexes with (quinolin-2-yl)methyl and discuss possible reasons of their inactivity in oxidation catalysis.

Design Rules for Binary Bisamide Gelators: toward Gels with Tailor-Made Structures and Properties.

This study intends to develop design rules for binary mixture of gelators that govern their assembly behavior and subsequently explore the impact of their supramolecular assembly patterns on the gels' rheological properties. To achieve these goals, nBA gelators with odd and even parities [n-methylene spacers between the amide groups (n = 5-10) and 17 carbons at each end] were blended at different ratios. Such bisamides with simple structures were selected to study because their different spacer lengths offer the possibility to have matching or non-matching hydrogen bonds. The results show that the assembly behavior of binary mixtures of bisamide gelators is the same in the solid and gel states. Binary mixtures of gelators, which only differ two methylene moieties in the spacer length, form compounds and co-assemble into fibers and sheets observed for (5BA)1(7BA)1 and (6BA)1(8BA)1 mixtures, respectively. Binary gelator mixtures of the same parity and a larger spacer length difference still lead to mixing for the odd parity couple (5BA)1(9BA)1), but to partial phase separation for the even parity mixture (6BA)1(10BA)1. Binary mixtures of gelators of different parities gave complete phase separation in the solid state, and self-sorted gels consisting of discrete fibers and sheets in the gels of (5BA)3(6BA)1 and (5BA)3(10BA)1. The even-even binary gels (20 wt %) consisting of co-assembled sheets show higher G' than odd-odd binary gels (20 wt %) consisting of co-assembled fibers. In general, the self-sorting of odd and even molecules into the separate primary structures results in a dramatic decrease of G' compared to the co-assembled gels (20 wt %), except for (5BA)1(9BA)1 gel (20 wt %). It might be due to larger woven spheres in (5BA)1(9BA)1 gel (20 wt %), which probably have a less entangled gel network.