Neutral Compounds Research Articles

2,2]Paracyclophane Bridged, Thiophene Based Macrocycles: Synthesis and Electronic Properties in Different Redox States.

The study of through-space electronic coupling in π-conjugated systems remains an underexplored area. In this work, we present the facile synthesis of two isomeric macrocycles (1 and 2) bridged by [2,2]paracyclophane (pCp) and based on thiophene. The structures of these macrocycles have been confirmed through X-ray crystallographic analysis. Our investigation centers on their electronic properties across various redox states, with a specific focus on potential through-space electronic coupling and global aromaticity. Experimental measurements, including UV-vis-NIR electronic absorption, NMR, ESR spectra, and X-ray diffraction, combined with theoretical calculations, reveal that both the neutral compounds and their tetracations exhibit a closed-shell ground state. However, their dications manifest as diradical dications with a subtle magnetic exchange interaction. Consequently, the through-space electronic coupling facilitated by the pCp unit in their respective ground states appears to be weak.

Sorption of pharmaceuticals to foam and aerobic granular sludge with different morphologies

In biological wastewater treatment, the sorption process is an important removal pathway of organic micropollutants from the aqueous phase. Beyond the conventional sorption to biomass and particulate matter, organic molecules can also partition to gas bubbles commonly present in aerated biological processes. This study investigated the partitioning behavior of 21 selected pharmaceuticals to two types of aerobic granular sludge, and the foam generated by aeration. Batch sorption experiments were performed with biologically inactive granules of controlled diameters (0.5–1, 1–2, and >2 mm). Removal during sorption tests was observed for four positively charged micropollutants (sertraline, citalopram, clarithromycin, and erythromycin), four neutral compounds (levonorgestrel, estradiol, ethinylestradiol, and ketoconazole), and one negatively charged pharmaceutical (losartan). This highlights the importance of electrostatic interactions and lipophilic affinity with the solids. For some compounds, the removal increased with time, suggesting that sorption in thick biofilm is limited by molecular diffusion into the biofilm matrix. Furthermore, partitioning of pharmaceuticals to aeration-induced foam was confirmed in separate batch tests. Clarithromycin, erythromycin, ketoconazole, losartan, levonorgestrel, and ethinylestradiol exhibited concentrations in the foam 1.0–5.3 times higher than the initial test values, indicating potential adsorption at the liquid/gas interface for these compounds.

Effects of Membrane Degradation due to Chlorine Exposure on the Removal of Neutral Organic Compounds by Reverse Osmosis for Potable Reuse

Effects of Membrane Degradation due to Chlorine Exposure on the Removal of Neutral Organic Compounds by Reverse Osmosis for Potable Reuse

Ability of biomimetic chromatography and physicochemical systems to predict the skin permeation of neutral compounds. A comparison study

Five in vitro physicochemical systems have been evaluated in terms of its ability to emulate the skin permeation of neutral compounds: the permeation in two different PAMPA membranes, the classical octanol-water partition coefficient, and two biomimetic chromatography systems, one based in cerasome electrokinetic chromatography and another based in reversed-phase liquid chromatography measurements.The coefficients of the solvation parameter model equation of the mentioned systems have been compared to the ones of the skin permeation process through different comparison parameters. Moreover, a method to predict whether a physicochemical system is able to emulate satisfactorily a biological one, just by the analysis of the equation coefficients has been developed. Results reveal that the two PAMPA systems are a good choice to emulate directly the skin permeation of neutral compounds. Instead, the other three systems need a volume correction term to provide a satisfactory emulation. However, after the correction, all the evaluated systems show a similar ability to emulate well skin permeation, as predicted.

Development, biological evaluation, and molecular modelling of some benzene-sulfonamide derivatives as protein tyrosine phosphatase-1B inhibitors for managing diabetes mellitus and associated metabolic disorders.

Exploring new inhibitors with good bioavailability and high selectivity for managing type 2 diabetes mellitus (T2DM) and its associated complications is a major challenge for research, academia, and the pharmaceutical industry. Protein tyrosine phosphatase-1B (PTP1B) arose as an important negative regulator in insulin signaling pathways associated with metabolic disorders, including T2DM and obesity. Novel neutral compounds with a benzene-sulfonamide scaffold were designed and synthesized based on structural- and ligand-based drug design strategies for fragment growth. Promising hits against PTP1B were identified through in vitro enzymology inhibition assay. Mechanistic aspects of the compound's different inhibition activities were rigorously investigated through molecular docking coupled with explicit dynamics simulations. Four identified hits, 3c, 8, 10a, and 11, with sub-micromolar PTP-1B IC50 and significant predicted pharmacokinetic and pharmacodynamic parameters, were further biologically evaluated for their anti-diabetic, anti-obesity, anti-inflammatory, and anti-oxidant effects in a high-fat diet (HFD) + streptozotocin (STZ)-induced T2DM rat model. All these hit compounds exhibited a significant anti-diabetic and anti-obesity effect and a significant efficacy in reducing oxidative stress and increasing anti-oxidant enzymes while reducing inflammatory markers. Improving compound potency was further highlighted by improving the pharmacokinetic profile of the most active compound, 10a, through nano formulation. Compound 10a nano formulation showed the most promising anti-diabetic and anti-obesity effects and a remarkable histopathological improvement in all organs studied.

Low coordinate Zn(II) organocations bearing extremely bulky NHC ligands: structural features, air-/water-tolerance and use in hydrosilylation and hydrogenation catalysis.

This work details the synthesis and characterization of low-coordinate Zn(II)-based organocations [(NHC)Zn(R)]+ incorporating extremely bulky NHCs [ITr] and [IAd] ([ITr] = ([ITr] = [(HCNCPh3)2C:]; [IAd] = [(HCNAd)2C:], Ad = adamantyl)). Their structural features and particularities are thoroughly assessed as well as their air and water tolerance. Neutral ITr and IAd adducts [(ITr)Zn(R)2] (1, R = Me; 2, R = Et) and [(IAd)Zn(R)2] (3, R = Me; 4, R = Et) were synthesized by reaction of carbene [ITr] or [IAd] with a stoichiometric amount of [ZnR2] and isolated in good yields. Despite the steric bulk of [ITr] and [IAd], neutral compounds 1-4 are robust and the solid state structure of adduct 3 was established through X-ray crystallographic studies as a trigonal monomer Zn(II) species. Adducts 1-4 may readily be ionized by [Ph3C][B(C6F5)4] to afford two-coordinate Zn(II) alkyl cations [(ITr)Zn(Me)]+ ([5]+) and [(ITr)Zn(Et)]+ ([6]+), [(IAd)Zn(Me)]+ ([7]+) and [(IAd)Zn(Me)]+ ([8]+), all isolated in high yields (>80%) as [B(C6F5)4]- salts, which were fully characterized. Remarkably, cation [(ITr)Zn(C6F5)]+ ([9]+), prepared by reaction of [5][B(C6F5)4] with [B(C6F5)3], features π-arene interactions with the electrophilic Zn(II), as deduced from solid state data and further completed by DFT-estimated non-covalent interactions (NCI), indicating that [ITr] may provide substantial steric and electrostatic stabilization. The latter certainly explains the remarkable stability of [(ITr)Zn(C6F5)]+ ([9]+) towards hydrolysis at RT, as it only coordinates H2O to afford an unprecedented stable Zn-OH2 organocation [10]+. Also noteworthy, H2O coordination is reversible allowing recovery of [(ITr)Zn(C6F5)]+ cation, even after prolonged air exposure. Yet, controlled hydrolysis of [(ITr)Zn(C6F5)]+ may occur upon heating with selective protonolysis of the Zn-C6F5 bond to afford structurally characterized dication [(ITr)Zn(OH)]22+ [11]2+. Interestingly, despite steric hindrance, the air-/water-tolerant cation [(ITr)Zn(C6F5)]+ is an effective CO2 hydrosilylation catalyst, and was also shown to mediate imine hydrogenation catalysis.

Reactions of the ˙NO3 radical with nuclear extraction ligands in alkane solution.

The reactivity of the nitrate radical (NO3˙) with organophosphorus and amidic actinide and lanthanide complexing agents of interest to nuclear solvent extraction applications was measured, resulting in the first-ever reported bimolecular rate constants for this radicals' reactions in dodecane solution. The order of reactivity for neutral organophosphorus compounds showed faster rate constants with increasing electron density on the phosphoryl phosphorus atom, indicating an increasing facility for electron abstraction reactions occurring in addition to H-atom abstraction from the ligand alkane chains. The only acidic organophosphorus compound investigated, HEH[EHP], showed low reactivity with the NO3˙ radical, attributed to its dimerization in this non-polar solvent. Amide ligand reaction rates were faster than for organophosphorus molecules, suggesting more facile H-atom abstraction from carbonyl activated methylene and amyl groups. While all rate constants were slower than the diffusion-limited rate they were still rapid enough to result in significant oxidation of solvent extraction ligands in dodecane solution.

Accurate prediction of Kp,uu,brain based on experimental measurement of Kp,brain and computed physicochemical properties of candidate compounds in CNS drug discovery

A mathematical equation model was developed by building the relationship between the fu,b/fu,p ratio and the computed physicochemical properties of candidate compounds, thereby predicting Kp,uu,brain based on a single experimentally measured Kp,brain value. A total of 256 compounds and 36 marketed published drugs including acidic, basic, neutral, zwitterionic, CNS-penetrant, and non-CNS penetrant compounds with diverse structures and physicochemical properties were involved in this study. A strong correlation was demonstrated between the fu,b/fu,p ratio and physicochemical parameters (CLogP and ionized fraction). The model showed good performance in both internal and external validations. The percentages of compounds with Kp,uu,brain predictions within 2-fold variability were 80.0 %–83.3 %, and more than 90 % were within a 3-fold variability. Meanwhile, “black box” QSAR models constructed by machine learning approaches for predicting fu,b/fu,p ratio based on the chemical descriptors are also presented, and the ANN model displayed the highest accuracy with an RMSE value of 0.27 and 86.7 % of the test set drugs fell within a 2-fold window of linear regression. These models demonstrated strong predictive power and could be helpful tools for evaluating the Kp,uu,brain by a single measurement parameter of Kp,brain during lead optimization for CNS penetration evaluation and ranking CNS drug candidate molecules in the early stages of CNS drug discovery.

Practical examination of flow rate effects and influence of the stationary phase water layer on peak shape and retention in Hydrophilic Interaction Liquid Chromatography.

The effect of flow velocity on retention and peak shape of neutral, acidic and basic probe compounds was studied using seven different UHPLC hydrophilic interaction chromatography (HILIC) columns. Surprisingly on some columns, the retention factor k was found to vary somewhat with flow velocity, due to the combined effects of pressure and of frictional heating on retention. The selectivity of different HILIC columns was much greater than typically found with RP columns. The volume of the water layer on the HILIC columns was measured using the toluene exclusion procedure. For the neutral solute uridine, a good correlation was found between the volume of the water layer and retention, indicating the likely domination of a partition mechanism. For the ionogenic solutes, the correlation was generally poor, due to the presence of strong additional mechanisms such as ionic retention and repulsion. Reduced van Deemter plots for uridine showed a negative correlation between the reduced b coefficient and the volume of the water layer, which can be attributed to reduced surface diffusion in this viscous layer. Once again, the behaviour of ionic solutes was complex on some columns making detailed interpretation difficult.

NHC aluminum chemistry on the rise.

This perspective highlights recent developments of the use of N-heterocyclic carbenes (NHCs) and cyclic (alkyl)(amino)carbenes (cAACs) in alane and aluminum organyl chemistry. Especially in the last few years this flourishing research field led to some remarkable discoveries including various substitution patterns at the central aluminum atom, different oxidation states, neutral and charged compounds with varying coordination numbers and unique reactivities. Thereby NHCs play a vital role in the stabilization of these otherwise highly reactive compounds, which would not be realizable without the use of this intriguing class of ligands. Nevertheless, main group hydrides and especially NHC ligated alanes also tend to undergo NHC decomposition reactions, which are part of ongoing research and provide important information for NHC research in general.

N-Methylene-C-linked nitropyrazoles and 1,2,4-triazol-3-one: thermally stable energetic materials with reduced sensitivity.

Recently, there has been a surge in research focusing on triazolone-based energetic materials, propelled by their remarkable properties such as good detonation performance as well as acceptable thermal and physical stability. In this work, a novel combination of the triazolone framework with dinitropyrazoles has been attained using the N-methylene-C-linked approach. Different substituents (NH2, NO2, N3, OH) were utilized on the dinitropyrazole moiety to obtain neutral energetic compounds 3-5 and 8. Furthermore, the hydroxy derivative (compound 8) facilitates the formation of energetic salts 9-13 to fine-tune the overall properties further. All the novel compounds 3-13 were thoroughly characterized by IR, multinuclear NMR spectroscopy, high-resolution mass spectrometry (HRMS), and elemental analysis. Compounds 3, 4, 8, and 10 were further confirmed via15N NMR spectroscopy. The structure of compounds 3 and 8 was also confirmed through single-crystal X-ray diffraction studies. The majority of synthesized compounds showed good thermal stability as well as insensitivity toward external stimuli. Computational studies, including analyses such as Hirshfeld surface, non-covalent interaction, electrostatic potential surface, and HOMO-LUMO analysis, were conducted to examine the influence of substitution at the 4th position on the overall stability of compounds 3, 4, and 8.

MINI REVIEW ON RECENT ADVANCES OF THE ADSORPTION MECHANISM BETWEEN MICROPLASTICS AND EMERGING CONTAMINANTS FOR CONSERVATION OF WATER

Pharmaceuticals and microplastics have long been identified as water pollutants. Pollutants, including pharmaceutical compounds, have been shown to be transported by microplastics (MPs). In this mini-review, adsorption mechanism between microplastics and emerging contaminants were highlighted. Polyethylene is a non-polar, semi-cystalline microplastic with a density of 240 to 244 kg/m3. Besides, Ibuprofen adsorption onto microplastics is pH dependent. Non-polar or neutral compounds that are homogeneous and extremely hydrophobic in nature interact with non-polar and weakly polar plastics such as Polypropylene and Polyethylene. Furthermore, Molecular dynamic (MD) simulation can be employed to study the mechanism of interaction between MPs and contaminants. As a result, some studies show a complex interaction between polyethylene (PE) and certain contaminants, with no significant differences in adsorption energies, but sulfamethazine molecules effectively adsorbed on the MPs surface. In summary, this mini review shed lights on the insights of adsorption mechanism between these compounds.

Metal-ligand interactions in a redox active ligand system. Electrochemistry and spectroscopy of [M(dipyvd)2]n+ (M=Zn, Ni, n=0, 1, 2).

Reaction of nickel and zinc triflates with the tridentate leucoverdazyl 1-isopropyl-3,5-di (2'-pyridyl)-6-oxo-2H-tetrazine (dipyvdH) and triethylamine resulted in the neutral coordination compounds M(dipyvd)2 (M = Ni,Zn). In acetonitrile, both compounds undergo two one electron oxidation processes, Zn (dipyvd)2at -0.28V and -0.12V and Ni(dipyvd)2at -0.32V and -0.15V vs ferrocene/ferricenium. Oxidations are ligand based resulting in an intermediate mixed valence species and a cationic bis(verdazyl) compound respectively. Oxidation of the ligand changes a localized, antiaromatic, non-planar 8π electron anion to a planar, delocalized 7π electron radical. The change in ligand structure results in an increase in the octahedral ligand field splitting from 10,500cm-1 to ∼13,000cm-1, suggesting an increase in the pi acceptor character of the ligand. In the mixed valence species, spectroscopic data suggests minimal interaction between ligands mediated by the metal center; i.e., these are class I-II systems in the Robin-Day classification.

Deciphering melting behaviors of energetic compounds using interpretable Machine learning for melt-castable applications

Melting behaviors of energetic compounds determine their thermo-responsive properties, which affects the manufacturing operations and structural stabilities. However, the decisive physicochemical mechanisms for melting behaviors of energetic compounds are absent, which hurdles the acceptancy and generalization of prediction models for rational molecular design. Herein, an interpretable machine learning (IML) approach was proposed to construct accurate prediction models for melting point values and melt-castable potentials of energetic compounds. A high-quality melting-point dataset comprising 239 neutral CHNO compounds was obtained, and the data was collected with strict criteria involving chemical formulations, crystal structures and experimental measurement operations. Tailored descriptors, which involve the priori insights for melting behaviors, were adopted for IML algorithms. The extreme gradient boosting model presents the best prediction accuracy (85 %) for the classification of melting point values between 273 K and 650 K; while 87 % accuracy is achieved for the classification of melt-castable property. Importantly, model interpretation assists to reveal that the close contacts between OC and NC, dipole, oxygen balance and the cohesive energy are decisive features for melting point prediction; while enthalpy of sublimation and polar surface area are paramount for the identification of melt-castable property. The ability to determine melting behaviors using IML will broaden the high-throughput screening of energetic compounds and offer valuable guidance towards molecular design.

Novel Models for Accurate Estimation of Air-Blood Partitioning: Applications to Individual Compounds and Complex Mixtures of Neutral Organic Compounds.

The air-blood partition coefficient (Kab) is extensively employed in human health risk assessment for chemical exposure. However, current Kab estimation approaches either require an extensive number of parameters or lack precision. In this study, we present two novel and parsimonious models to accurately estimate Kab values for individual neutral organic compounds, as well as their complex mixtures. The first model, termed the GC×GC model, was developed based on the retention times of nonpolar chemical analytes on comprehensive two-dimensional gas chromatography (GC×GC). This model is unique in its ability to estimate the Kab values for complex mixtures of nonpolar organic chemicals. The GC×GC model successfully accounted for the Kab variance (R2 = 0.97) and demonstrated strong prediction power (RMSE = 0.31 log unit) for an independent set of nonpolar chemical analytes. Overall, the GC×GC model can be used to estimate Kab values for complex mixtures of neutral organic compounds. The second model, termed the partition model (PM), is based on two types of partition coefficients: octanol to water (Kow) and air to water (Kaw). The PM was able to effectively account for the variability in Kab data (n = 344), yielding an R2 value of 0.93 and root-mean-square error (RMSE) of 0.34 log unit. The predictive power and explanatory performance of the PM were found to be comparable to those of the parameter-intensive Abraham solvation models (ASMs). Additionally, the PM can be integrated into the software EPI Suite, which is widely used in chemical risk assessment for initial screening. The PM provides quick and reliable estimation of Kab compared to ASMs, while the GC×GC model is uniquely suited for estimating Kab values for complex mixtures of neutral organic compounds. In summary, our study introduces two novel and parsimonious models for the accurate estimation of Kab values for both individual compounds and complex mixtures.

Insensitive energetic compounds based on regioisomeric nitro-substituted fused triazole

Two series of nitro-substituted fused triazole were prepared. All compounds have been fully characterized by IR, elemental analysis, 1H and 13C NMR, and DSC. Neutral compounds a1 and b1 exhibit quite different thermostabilities and this trend has extended to their energetic salts, which could be explained by the NBO analysis and hydrogen bonds based on the single-crystal parameters. The structures of salts a2, a3, and b3 were also confirmed by single-crystal X-ray diffraction. NCI and Hirshfeld surface analysis were performed to further understand the relationship between properties and regioisomeric structures. All new compounds show good densities varying within 1.66–1.83 g cm−3, detonation velocities varying within 7688-8461 m s−1, and detonation pressures varying within 22.1–26.7 Gpa, and are insensitive to friction and impact. High thermal stability (Td = 274 °C) combined with good detonation velocity (vD = 8238 m s−1) highlight the promising application for salt b2 as a high-energy insensitive compound.

A Neutral Planar Four-Membered Si2B2 2π-Aromatic Ring.

The synthesis of the first inorganic four-membered neutral 2π-aromatic compound 2 is reported. This unique ring has been synthesized from a simple and straightforward reaction of amidinato-silylene with dichlorophenylborane, followed by the reduction with KC8 in THF. Compound 2 has been fully characterized by single-crystal X-ray diffraction (SC-XRD), NMR spectroscopy, and mass spectrometry. The computational calculations reveal that the Si2B2 ring is a π-delocalized system resulting from the interaction of pπ orbital of B and Si-N σ* orbitals having pseudo π symmetry. Compound 2 is the first known example of a neutral planar inorganic analogue of cyclobutenyl dication.

Understanding and predicting the adsorption and rejection of pesticides and metabolites by hollow fiber nanofiltration membranes

Layer-by-layer Hollow fiber Nanofiltration (LbL HF-NF) membranes have shown great potential in the removal of micropollutants from water. Nonetheless, further research is required as the number of tested compounds remains limited. In this study, the adsorption and rejection of 164 micropollutants by two commercial HF-NF membranes with MWCO of 400 and 800 Da, were investigated. The investigation was conducted by evaluating the influence of 11 physicochemical micropollutants’ properties on the separation performances. Results showed that highly adsorbed compounds had average log D values above 3, while no or low adsorption was observed for compounds with negative log D values. Furthermore, adsorption was more frequently observed for neutral compounds compared to negatively charged ones. Micropollutants rejection results showed that steric exclusion plays the most important role in the rejection of micropollutants, and that the charge of micropollutants can also heavily influence their rejection. Likewise, negatively charged compounds were better rejected than neutral ones. Finally, the study demonstrated that adsorption and rejection of micropollutants can be predicted with good accuracy using the random forest algorithm. The prediction accuracy for adsorption was 80% and 73% for the 800 and 400 Da MWCO membranes, respectively. The RMSE for rejection predictions was 10.6% and 6% for the two membranes respectively.

Complexes on the Base of a Proton Transfer Capable Pyrimidine Derivative: How Protonation and Deprotonation Switch Emission Mechanisms.

A rare example of pyrimidine-based ESIPT-capable compounds, 2-(2-hydroxyphenyl)-4-(1H-pyrazol-1-yl)-6-methylpyrimidine (HLH), was synthesized (ESIPT─excited state intramolecular proton transfer). Its reactions with zinc(II) salts under basic or acidic conditions afforded a dinuclear [Zn2LH2Cl2] complex and an ionic (H2LH)4[ZnCl4]2·3H2O solid. Another ionic solid, (H2LH)Br, was obtained from the solution of HLH acidified with HBr. In both ionic solids, the H+ ion protonates the same pyrimidinic N atom that accepts the O-H···N intramolecular hydrogen bond in the structure of free HLH, which breaks this hydrogen bond and switches off ESIPT in these compounds. This series of compounds which includes neutral HLH molecules and ionic (LH)- and (H2LH)+ species allowed us to elucidate the impact of protonation and coordination coupled deprotonation of HLH on the photoluminescence response and on altering the emission mechanism. The neutral HLH compound exhibits yellow emission as a result of the coexistence of two radiative decay channels: (i) T1 → S0 phosphorescence of the enol form and (ii) anti-Kasha S2 → S0 fluorescence of the keto form, which if feasible due to the large S2-S1 energy gap. However, owing to the efficient nonradiative decay through an energetically favorable conical intersection, the photoluminescence quantum yield of HLH is low. Protonation or deprotonation of the HLH ligand results in the significant blue-shift of the emission bands by more than 100 nm and boosts the quantum efficiency up to ca. 20% in the case of [Zn2LH2Cl2] and (H2LH)4[ZnCl4]2·3H2O. Despite both (H2LH)4[ZnCl4]2·3H2O and (H2LH)Br have the same (H2LH)+ cation in the structures, their emission properties differ significantly, whereas (H2LH)Br shows dual emission associated with two radiative decay channels: (i) S1 → S0 fluorescence and (ii) T1 → S0 phosphorescence, (H2LH)4[ZnCl4]2·3H2O exhibits only fluorescence. This difference in the emission properties can be associated with the external heavy atom effect in (H2LH)Br, which leads to faster intersystem crossing in this compound. Finally, a huge increase in the intensity of the phosphorescence of (H2LH)Br on cooling leads to pronounced luminescence thermochromism (violet emission at 300 K, sky-blue emission at 77 K).

Detection of qacΔE Efflux Pump Gene among the Clinical Isolates of Escherichia coli and its Correlation with Resistance to Disinfectants.

Disinfectants and antiseptics inhibit the dissemination of pathogenic organisms in hospitals but often cause disinfectant-resistant microorganisms, an important factor for nosocomial infection. This study aimed to evaluate the correlation between qacΔE efflux pump gene and its resistance to disinfectants among Escherichia coli clinical isolates. A total of 97 E. coli isolates were isolated from patients with urinary tract infections. The minimum inhibition concentration (MIC) value of chlorhexidine and benzalkonium chloride was determined using broth microdilution method. Effect of efflux pumps was assessed by MIC test in the presence of phenylalanine-arginine β-naphthylamide (PAβN), and then the qacΔE efflux pump gene was detected using polymerase chain reaction (PCR). Of the isolates, 85.6% and 61.9% were resistant to chlorhexidine and benzalkonium chloride, respectively. Following the treatment of isolates with the efflux pump's inhibitor, PAβN, the MIC value of chlorhexidine and benzalkonium chloride decreased in 75.2% and 57.7% of the isolates, respectively. A significant correlation was found between PAβN treatment and the change in the resistant strains to susceptible strains (p = 0.021). The qacΔE gene was detected in 84.5% (n = 82) of the isolates, and the presence of the gene amongst disinfectant-resistant strains was also significant (p < 0.001). It is suggested to conduct other studies on other efflux pumps, as well as to periodically monitor the resistance to disinfectants. Substances inhibiting efflux pumps and neutral compounds are effective in the reduction of resistance to disinfectants. New disinfectants and drugs should be designed.