Charge-transfer chemistry of two corticosteroids used adjunctively to treat COVID-19. Part I: Complexation of hydrocortisone and dexamethasone donors with DDQ acceptor in five organic solvents.

COVID-19 is the disease caused by a novel coronavirus (CoV) named the severe acute respiratory syndrome coronavirus 2 (termed SARS coronavirus 2 or SARS-CoV-2). Since the first case reported in December 2019, infections caused by this novel virus have led to a continuous global pandemic that has placed an unprecedented burden on health, economic, and social systems worldwide. In response, multiple therapeutic options have been developed to stop this pandemic. One of these options is based on traditional corticosteroids, however, chemical modifications to enhance their efficacy remain largely unexplored. Obtaining additional insight into the chemical and physical properties of pharmacologically effective drugs used to combat COVID-19 will help physicians and researchers alike to improve current treatments and vaccines (i.e., Pfizer-BioNTech, AstraZeneca, Moderna, Janssen). Herein, we examined the charge-transfer properties of two corticosteroids used as adjunctive therapies in the treatment of COVID-19, hydrocortisone and dexamethasone, as donors with 2,3-dichloro-5,6-dicyano-p-benzoquinone as an acceptor in various solvents. We found that the examined donors reacted strongly with the acceptor in CH2Cl2 and CHCl3 solvents to create stable compounds with novel clinical potential.

Charge-transfer chemistry of two corticosteroids used adjunctively to treat COVID-19. Part II: The CT reaction of hydrocortisone and dexamethasone donors with TCNQ and fluoranil acceptors in five organic solvents.

Hydrocortisone (termed as D1) and dexamethasone (termed as D2) are corticosteroids currently used to treat COVID-19. COVID-19 is a disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Exploring additional chemical properties of drugs used in the treatment protocols for COVID-19 could help scientists alike improve these treatment protocols and potentially even the vaccines (i.e., Janssen, Moderna, AstraZeneca, Pfizer-BioNTech). In this work, the charge-transfer (CT) properties of these two corticosteroids (D1 and D2) with two universal acceptors: 7,8,8-tetracyanoquinodimethane (termed as TCNQ) and fluoranil (termed as TFQ) in five different solvents were investigated. The examined solvents were MeOH, EtOH, MeCN, CH2Cl2, and CHCl3. The CT interactions formed stable corticosteroid CT complexes in all examined solvents. Several spectroscopic parameters were derived, and the oscillator strength (f) and transition dipole moment (µe.g. ) values revealed that the interaction between the investigated corticosteroids with TCNQ acceptor is much stronger than their interaction with TFQ acceptor. The CT interactions were proposed to process via n â†’ π* transition.

Charge-transfer chemistry of azithromycin, the antibiotic used worldwide to treat the coronavirus disease (COVID-19). Part I: Complexation with iodine in different solvents.

Around the world, the antibiotic azithromycin (AZM) is currently being used to treat the coronavirus disease (COVID-19) in conjunction with hydroxychloroquine or chloroquine. Investigating the chemical and physical properties of compounds used alone or in combination to combat the COVID-19 pandemic is of vital and pressing importance. The purpose of this study was to characterize the charge transfer (CT) complexation of AZM with iodine in four different solvents: CH2Cl2, CHCl3, CCl4, and C6H5Cl. AZM reacted with iodine at a 1:1 M ratio (AZM to I2) in the CHCl3 solvent and a 1:2 M ratio in the other three solvents, as evidenced by data obtained from an elemental analysis of the solid CT products and spectrophotometric titration and Job's continuous variation method for the soluble CT products. Data obtained from UV-visible and Raman spectroscopies indicated that AZM strongly interacted with iodine in the CH2Cl2, CCl4, and C6H5Cl solvents by a physically potent n→σ* interaction to produce a tri-iodide complex formulated as [AZM·I+]I3 -. XRD and TEM analyses revealed that, in all solvents, the AZM-I2 complex possessed an amorphous structure composed of spherical particles ranging from 80 to 110 nm that tended to aggregate into clusters. The findings described in the present study will hopefully contribute to optimizing the treatment protocols for COVID-19.

Charge-transfer chemistry of azithromycin, the antibiotic used worldwide to treat the coronavirus disease (COVID-19). Part III: A green protocol for facile synthesis of complexes with TCNQ, DDQ, and TFQ acceptors.

Investigating the chemical properties of molecules used to combat the COVID-19 pandemic is of vital and pressing importance. In continuation of works aimed to explore the charge-transfer chemistry of azithromycin, the antibiotic used worldwide to treat COVID-19, the disease resulting from infection with the novel SARS-CoV-2 virus, in this work, a highly efficient, simple, clean, and eco-friendly protocol was used for the facile synthesis of charge-transfer complexes (CTCs) containing azithromycin and three π-acceptors: 7,7,8,8-tetracyanoquinodimethane (TCNQ), 2,3-dichloro-5,6-dicyano-p-benzoquinone (DDQ), and tetrafluoro-1,4-benzoquinone (TFQ). This protocol involves grinding bulk azithromycin as the donor (D) with the investigated acceptors at a 1:1 M ratio at room temperature without any solvent. We found that this protocol is environmentally benign, avoids hazardous organic solvents, and generates the desired CTCs with excellent yield (92-95%) in a straightforward means.

Charge-transfer chemistry of azithromycin, the antibiotic used worldwide to treat the coronavirus disease (COVID-19). Part II: Complexation with several π-acceptors (PA, CLA, CHL).

Finding a vaccine or cure for the coronavirus disease (COVID-19) responsible for the worldwide pandemic and its economic, medical, and psychological burdens is one of the most pressing issues presently facing the global community. One of the current treatment protocols involves the antibiotic azithromycin (AZM) alone or in combination with other compounds. Obtaining additional insight into the charge-transfer (CT) chemistry of this antibiotic could help researchers and clinicians to improve such treatment protocols. Toward this aim, we investigated the CT interactions between AZM and three π-acceptors: picric acid (PA), chloranilic acid (CLA), and chloranil (CHL) in MeOH solvent. AZM formed colored products at a 1:1 stoichiometry with the acceptors through intermolecular hydrogen bonding. An n â†’ π* interaction was also proposed for the AZM-CHL CT product. The synthesized CT products had markedly different morphologies from the free reactants, exhibiting a semi-crystalline structure composed of spherical particles with diameters ranging from 50 to 90 nm.

Association of vitamin D receptor gene FokI polymorphism and susceptibility to CAP in Egyptian children: a multicenter study.

BACKGROUND: Community-acquired pneumonia (CAP) is the leading cause of child deaths around the world. Recently, the vitamin D receptor (VDR) gene has emerged as a susceptibility gene for CAP. OBJECTIVES: To evaluate the association of the VDR gene Fok I polymorphism with susceptibility to CAP in Egyptian children. METHODS: This was a multicenter case-control study of 300 patients diagnosed with CAP, and 300 well-matched healthy control children. The VDR Fok I (rs2228570) polymorphism was genotyped by PCR-restriction fragment length polymorphism (RFLP), meanwhile serum 25-hydroxy vitamin D (25D) level was assessed using ELISA method. RESULTS: The frequencies of the VDR FF genotype and F allele were more common in patients with CAP than in our control group (OR = 3.6; (95% CI: 1.9-6.7) for the FF genotype; P = 0.001) and (OR: 1.8; (95% CI: 1.4-2.3) for the F allele; P = 0.01). Patients carrying the VDR FF genotype had lower serum (25D) level (mean; 14.8 ± 3.6 ng/ml) than Ff genotype (20.6 ± 4.5 ng/ml) and the ff genotype (24.5 ± 3.7 ng/ml); P < 0.01. CONCLUSION: The VDR gene Fok I (rs2228570) polymorphism confers susceptibility to CAP in Egyptian children.

Charge-transfer interaction of aspartame and neotame with several π-acceptors: Stoichiometric data.

This data article is related to a research paper entitled ``Correlations between spectroscopic data for charge-transfer complexes of two artificial sweeteners, aspartame and neotame, generated with several π-acceptors'' [J. Mol. Liq. 333 (2021) 115904] [1]. Herein we present stoichiometric data of charge-transfer (CT) complexes generated from the interaction between aspartame and neotame with three π-acceptors in methanol solvent at room temperature. The investigated π-acceptors were picric acid (PA), chloranilic acid (CA), and 2,3-dichloro-5,6-dicyano-p-benzoquinone (DDQ), where the methods used to determine the stoichiometry of the CT interaction were the spectrophotometric titration method and the Job's continuous variation method.

Data on charge-transfer interaction between 1-methyl-3-trifluoromethyl-2-pyrazoline-5-one with PA, CLA, TFQ, DDQ and TCNQ π-acceptors.

This article is related to a research paper entitled "Exploring the charge-transfer chemistry of fluorine-containing pyrazolin-5-ones: The complexation of 1-methyl-3-trifluoromethyl-2-pyrazoline-5-one with five π-acceptors" [J. Mol. Liq. 331 (2021) 115814] [1]. Herein we present photographic data that showed the color change after mixing methanolic solutions of 1-methyl-3-trifluoromethyl-2-pyrazoline-5-one (donor) with each of the investigated π-acceptor [picric acid (PA), chloranilic acid (CLA), fluoranil (TFQ), DDQ, and TCNQ]. Stoichiometry data for the interaction of the donor with all acceptors determined in solution state by the spectrophotometric titration method and the Job's continuous variation method were presented. The data presented are useful for understand that the charge-transfer (CT) complexation between a donor and an acceptor, generally, is characterized by a strong color change, and to understand the stoichiometry between these molecules.

Measurements and correlations in solution-state for charge transfer products caused from the 1:2 complexation of TCNE acceptor with several important drugs.

In our previous work, we highlighted the thermodynamic and spectroscopic characteristics of the 1:1 charge transfer (CT) complexation of TCNE acceptor with various medically important drugs. Continuing that work, we further examine drugs that react with the TCNE acceptor via a 1:2 interaction. The examined drugs are atenolol, quinidine, cimetidine, reserpine, and levofloxacin. We aimed through this study to: i) make the spectrophotometric and thermodynamic data of the examined drugs, both initially and when reacted via a 1:2 M ratio with the TCNE acceptor, available to use in the determination or detection of these drugs in pharmaceuticals and other environments; and ii) compare the mode of interactions and the spectrophotometric and thermodynamic properties between drugs that react via a 1:1 or 1:2 ratio with the TCNE acceptor. To achieve these aims, the five examined drugs were reacted with TCNE in acetonitrile (MeCN) solvent at room temperature. Several thermodynamic and spectroscopic data were experimentally estimated using the van't Hoff and the Benesi-Hildebrand equations and discussed.

Interleukin-4 -590C/T gene polymorphism in Egyptian children with acute lower respiratory infection: A multicenter study.

BACKGROUND: Acute lower respiratory infection (ALRI) is the leading cause of child mortality, especially in the developing world. Polymorphisms in the interleukin 4 (IL-4) gene have been linked to a variety of human diseases. OBJECTIVES: To investigate whether the IL-4 -590C/T (rs2243250) polymorphism could be a genetic marker for susceptibility to ALRIs in young Egyptian children. METHODS: This was a multicenter study conducted on 480 children diagnosed with pneumonia or bronchiolitis, and 480 well-matched healthy control children. Using PCR-RFLP analysis, we genotyped a -590C/T (rs2243250) single nucleotide polymorphism of the IL-4 gene promoter, meanwhile the serum IL-4concentration was measured by ELISA. RESULTS: The frequency of the IL-4 -590 T/T genotype and T allele were overrepresented in patients with ALRIs in comparison to the control group (OR = 2.0; [95% confidence interval [CI]: 1.38-2.96]; for the T/T genotype) and (OR: 1.3; [95%CI: 1.07-1.56]; for the T allele; P < 0.01). The IL-4 -590 T/T genotype was associated with significantly higher mean serum IL-4 concentration (58.7 ± 13.4 pg/mL) compared to the C/T genotype (47.6 ± 11 pg/mL) and the C/C genotype (34.8 ± 9.6 pg/mL); P < 0.01. CONCLUSION: The IL-4 -590C/T (rs2243250) polymorphism may contribute to susceptibility to ALRIs in young Egyptian children.

Angiotensin-converting enzyme insertion/deletion gene polymorphism in Egyptian children with CAP: A case-control study.

BACKGROUND: Community-acquired pneumonia (CAP) is a major cause of childhood morbidity and mortality worldwide. The angiotensin-converting enzyme (ACE) gene is a potential candidate gene for CAP risk. OBJECTIVES: In this study, we aimed to investigate whether the ACE insertion/deletion (I/D) polymorphism (rs4340) could be a genetic marker for CAP susceptibility in Egyptian children, and we also measured the serum ACE level to assess its relation to such polymorphism. METHODS: This was a prospective case-control study included 300 patients with CAP, and 300 age, gender, and ethnicity matched healthy controls. The ACE I/D polymorphism (rs4340) at intron 16 was genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), while the serum ACE levels were measured by ELISA. RESULTS: Compared to the controls subjects, the frequencies of the ACE DD genotype and D allele were overrepresented in patients with CAP (OR = 3.05; [95%CI: 2.14-4.35] for the DD genotype; P < 0.001) and (OR: 1.8; [95%CI: 1.42-2.29]; for the D allele; P < 0.01, respectively). Patients with the DD genotype had significantly higher mean serum ACE levels (45.6 ± 11.4 U/L) compared to those with ID genotype (36.5 ± 8.3 U/L) and II genotype (21.6 ± 5.7 U/L); P < 0.01, respectively. CONCLUSION: The ACE I/D polymorphism (rs4340) may contribute to the genetic susceptibility of CAP in Egyptian children. The ACE D allele and DD genotype were associated with higher serum ACE levels among studied CAP patients.

Interleukin-1ß and interleukin-1receptor antagonist polymorphisms in Egyptian children with febrile seizures: A case-control study.

Febrile seizure is the most common seizure disorder of childhood. Of the pro-inflammatory cytokines, interleukin-1 is defined as the first endogenous pyrogen.We designed this study to investigate single-nucleotide polymorphisms (SNPs) situated at positions -31 (C/T), and -511 (C/T) of interleukin-1beta (IL-1ß) gene promoter and interleukin-1receptor antagonist (IL-1RA) gene variable number of tandem repeats in intron 2 (VNTR); to determine whether these polymorphisms could be a marker of susceptibility to febrile seizures in Egyptian children and we also measured the serum level of IL-1ß to assess its relation to such polymorphisms.This was a case-control study included 155 patients with febrile seizure, and matched with age, sex, ethnicity 155 healthy control subjects. IL-1ß promoter at positions -31 (C/T), -511 (C/T), and IL-1RA gene VNTR polymorphisms were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), while the serum IL-1ß levels were measured by enzyme-linked immunosorbent assay (ELISA) method.The frequency of the IL-1ß-511 TT genotype and T allele at the same position were observed to be increased in patients with febrile seizures (FS) compared with the control group (odds ratio [OR]: 3.96; 95% confidence interval [CI]: 1.68-9.5; P = 0.001 for the TT genotype and OR: 1.65; 95% CI: 1.18-2.3; P = 0.003 for the T allele, respectively). The IL-1 RA II/II homozygous variant and IL-1 RA allele II were overrepresented in patients with FS than control group (OR: 4.02; 95% CI: 1.78-9.15; P = 0.001and OR: 1.73; 95% CI: 1.24-2.4; P = 0.001, respectively). We found a significant positive association between the IL-1 RA II/II genotype and susceptibility to FS in sporadic cases as did allele II at the same position (OR: 5.04; 95% CI: 2.1-12.5 for the IL-1 RA II/II genotype; P = 0.001) and (OR: 1.94; 95% CI: 1.3-2.8 for the allele II; P = 0.001, respectively). Carriers of the IL-1RA II/II homozygous variant and allele II had significantly higher serum levels of IL-1ß compared with those with other genotypes and alleles.We demonstrate for the first time that the presence of a T allele or TT genotype at -511 of IL-1ß promoter and IL-1RA II/II genotype constitute risk factors for developing FS in Egyptian children.