Heteroacene-Based Polymer with Fast-Switching Visible-Near Infrared Electrochromic Behavior.

The electrochromic properties and application of electronically conducting polymers (ECPs) (PTRPZ-EDOT) consisting of a 3,4-ethylenedioxythiophene (EDOT) and the heteroacene-based molecular scaffold, 6H-pyrrolo[3,2-b:4,5-b'] bis [1,4] benzothiazine (TRPZ), are reported. Known for its high electron mobility and conducting properties, the novel TRPZ scaffold was synthesized to possess two EDOT molecules termini affording TRPZ-EDOT. Electropolymerization of TRPZ-EDOT resulted in remarkable spectroscopic and conductive properties suitable for electrochromic device fabrication. Using atomic force microscopy (AFM), the average surface roughness and surface topography of PTRPZ-EDOT polymer thin films were determined. Spectroelectrochemical data showed that the polymer achieved switching times of 4.07 (coloration) and 0.47 s (bleaching) at 539 nm. The PTRPZ-EDOT film exhibits an optical contrast of 36-44% at 539 nm between its neutral and colored states, respectively. The NIR region from 1000 to 1700 nm shows the appearance of charge carrier bands with a 0-1 V potential range. An electrochromic device was successfully fabricated from PTRPZ-EDOT, showcasing the potential and applicability of the polymer material for advanced technologies such as smart windows, flexible electrochromic screens, and energy storage devices.

Investigation of cannabidiol's potential targets in limbic seizures. In-silico approach.

Even though the vast armamentarium of FDA-approved antiepileptic drugs is currently available, over one-third of patients do not respond to medication, which arises a need for alternative medicine. In clinical and preclinical studies, various investigations have shown the advantage of specific plant-based cannabidiol (CBD) products in treating certain groups of people with limbic epilepsy who have failed to respond to conventional therapies. This work aims to investigate possible mechanisms by which CBD possesses its anticonvulsant properties. Molecular targets for CBD's treatment of limbic epilepsy, including hyperpolarization-activated cyclic nucleotide-gated channel 1 (HCN1), gamma-aminobutyric acid aminotransferase (GABA-AT), and gamma-aminobutyric acid type A receptor (GABAA), were used to evaluate its binding affinity. Interactions with the CB1 receptor were initially modeled as a benchmark, which further proved the efficiency of proposed here approach. Considering the successful benchmark, we further used the same concept for in silico investigation, targeting proteins of interest. As a result of molecular docking, molecular mechanics, and molecular dynamics simulations models of CBD-receptor complexes were proposed and evaluated. While CBD possessed decently high affinity and stability within the binding pockets of GABA-AT and some binding sites of GABAA, the most effective binding was observed in the CBD complex with HCN1 receptor. 100 ns molecular dynamics simulation revealed that CBD binds the open pore of HCN1 receptor, forming a similar pattern of interactions as potent Lamotrigine. Therefore, we can propose that HCN1 can serve as a most potent target for cannabinoid antiepileptic treatment. Communicated by Ramaswamy H. Sarma.

Homology Modeling and Molecular Dynamics-Driven Search for Natural Inhibitors That Universally Target Receptor-Binding Domain of Spike Glycoprotein in SARS-CoV-2 Variants.

The rapid spread of SARS-CoV-2 required immediate actions to control the transmission of the virus and minimize its impact on humanity. An extensive mutation rate of this viral genome contributes to the virus' ability to quickly adapt to environmental changes, impacts transmissibility and antigenicity, and may facilitate immune escape. Therefore, it is of great interest for researchers working in vaccine development and drug design to consider the impact of mutations on virus-drug interactions. Here, we propose a multitarget drug discovery pipeline for identifying potential drug candidates which can efficiently inhibit the Receptor Binding Domain (RBD) of spike glycoproteins from different variants of SARS-CoV-2. Eight homology models of RBDs for selected variants were created and validated using reference crystal structures. We then investigated interactions between host receptor ACE2 and RBDs from nine variants of SARS-CoV-2. It led us to conclude that efficient multi-variant targeting drugs should be capable of blocking residues Q(R)493 and N487 in RBDs. Using methods of molecular docking, molecular mechanics, and molecular dynamics, we identified three lead compounds (hesperidin, narirutin, and neohesperidin) suitable for multitarget SARS-CoV-2 inhibition. These compounds are flavanone glycosides found in citrus fruits - an active ingredient of Traditional Chinese Medicines. The developed pipeline can be further used to (1) model mutants for which crystal structures are not yet available and (2) scan a more extensive library of compounds against other mutated viral proteins.

Heteroacene-Based Amphiphile as a Molecular Scaffold for Bioimaging Probes.

The challenges faced with current fluorescence imaging agents have motivated us to study two nanostructures based on a hydrophobic dye, 6H-pyrrolo[3,2-b:4,5-b']bis [1,4]benzothiazine (TRPZ). TRPZ is a heteroacene with a rigid, pi-conjugated structure, multiple reactive sites, and unique spectroscopic properties. Here we coupled TRPZ to a tert-butyl carbamate (BOC) protected 2,2-bis(hydroxymethyl)propanoic acid (bisMPA) dendron via azide-alkyne Huisgen cycloaddition. Deprotection of the protected amine groups on the dendron afforded a cationic terminated amphiphile, TRPZ-bisMPA. TRPZ-bisMPA was nanoprecipitated into water to obtain nanoparticles (NPs) with a hydrodynamic radius that was <150 nm. For comparison, TRPZ-PG was encapsulated in pluronic-F127 (Mw = 12 kD), a polymer surfactant to afford NPs almost twice as large as those formed by TRPZ-bisMPA. Size and stability studies confirm the suitability of the TRPZ-bisMPA NPs for biomedical applications. The photophysical properties of the TRPZ-bisMPA NPs show a quantum yield of 49%, a Stokes shift of 201 nm (0.72 eV) and a lifetime of 6.3 ns in water. Further evidence was provided by cell viability and cellular uptake studies confirming the low cytotoxicity of TRPZ-bisMPA NPs and their potential in bioimaging.

N-arylnaphthylamines as inhibitors of human immunodeficiency virus integrase - lens epithelium-derived growth factor interactions: theoretical studies.

Presented work reports a comprehensive theoretical study on the inhibitory nature of N-arylnaphthylamines in Human Immunodeficiency Virus Integrase (HIV IN) - Lens Epithelium-Derived Growth Factor (LEDGF/p75) complexes. Factors influencing the inhibition efficiency in AlphaScreen% assay are evaluated and explained through the structure- and ligand-based studies; including molecular docking, molecular dynamics calculations, and quantitative structure-activity relationship (QSAR) approach. It has been shown that N-arylnaphthylamines possess a wide variety of binding poses. Three QSAR models have been developed using structural descriptors and descriptors derived from docking calculations. The activity of untested N-arylnaphthylamines have been predicted using the most successful model. Proposed here technique could become a useful tool for ligand selection, accelerating the development of a new generation of anti-HIV medications. [Formula: see text] Communicated by Ramaswamy H. Sarma.

Protein reliability analysis and virtual screening of natural inhibitors for SARS-CoV-2 main protease (Mpro) through docking, molecular mechanic & dynamic, and ADMET profiling.

Due to an outbreak of COVID-19, the number of research papers devoted to in-silico drug discovery of potential antiviral drugs is increasing every day exponentially. Still, there is no specific drug to prevent or treat this novel coronavirus (SARS-CoV-2) disease. Thus, the screening for a potential remedy presents a global challenge for scientists. Up to date over a hundred crystallographic structures of SARS-CoV-2 Mpro have been deposited to Protein Data Bank. With many known proteins, the demand for a reliable target has become higher than ever, so as the choice of an efficient computational methods. Therefore, in this study comparative methods have been used for receptor-based virtual screening, targeting 9 selected structures of viral Mpro. Reliability analyses followed by re-docking of the specific co-crystallized ligand provided the best reproductivity for structures with PDB ID 6LU7, 6Y2G and 6Y2F. The influence of crystallographic water on an outcome of a virtual screening against selected targets was also investigated. Once the most reliable targets were selected, the library of easy purchasable natural compounds were retrieved from the MolPort database (10,305 compounds) and docked against the selected Mpro proteins. To ensure the efficiency of the selected compounds, binding energies for top-15 hit ligands were calculated using Molecular Mechanics as well as their absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties were predicted. Based on predicted binding energies and toxicities, top-5 compounds were selected and subjected to Molecular Dynamics simulation and found to be stable in complex to act as possible inhibitors for SARS-CoV-2. Communicated by Ramaswamy H. Sarma.

Antioxidant Activity of Selected Phenolic Acids-Ferric Reducing Antioxidant Power Assay and QSAR Analysis of the Structural Features.

Phenolic acids are naturally occurring compounds that are known for their antioxidant and antiradical activity. We present experimental and theoretical studies on the antioxidant potential of the set of 22 phenolic acids with different models of hydroxylation and methoxylation of aromatic rings. Ferric reducing antioxidant power assay was used to evaluate this property. 2,3-dihydroxybenzoic acid was found to be the strongest antioxidant, while mono hydroxylated and methoxylated structures had the lowest activities. A comprehensive structure-activity investigation with density functional theory methods elucidated the influence of compounds topology, resonance stabilization, and intramolecular hydrogen bonding on the exhibited activity. The key factor was found to be a presence of two or more hydroxyl groups being located in ortho or para position to each other. Finally, the quantitative structure-activity relationship approach was used to build a multiple linear regression model describing the dependence of antioxidant activity on structure of compounds, using features exclusively related to their topology. Coefficients of determination for training set and for the test set equaled 0.9918 and 0.9993 respectively, and Q2 value for leave-one-out was 0.9716. In addition, the presented model was used to predict activities of phenolic acids that haven't been tested here experimentally.

Synthesis and antiproliferative activity in vitro of new 2-thioxoimidazo[4,5-B]pyridine derivatives.

Two series of 2-thioxoimidazo[4,5-b]pyridine derivatives have been synthesized from 2,3-diaminopyridine (1) and 5-halogenosubstituted-2,3-diaminopyridines 2, 3. Mannich bases 7 - 12 and 24 - 29, derivatives of 1-arylamino-6-halogeno-2-thioxoimidazo[4,5-b]pyridine were obtained with selected secondary amines: morpholine, piperidine, 2-methoxyphenylpiperazine, pyrimidyn-2-yl-piperazine and formaldehyde in ethanol. The structures 7 - 12 and 24 - 29 were confirmed by the results of elementary analysis and their IR, 1H-NMR and MS spectra. All given structures 7 - 12 have been optimized to get the most stable low energy conformers. Synthesized compounds were of interest for biological studies or can be substrates for further synthesis. The selected compounds 7 - 10, 12- 17, 22, 25, 27 - 29 were screened for their antiproliferative activity in vitro against human cancer and normal mouse fibroblast cell lines.

Multi-procedure management in an eyeglasses-related open globe injury.

We present a case of successful multi-procedure management of a patient with an open globe injury. A 47-year-old man sustained an injury to his left eye caused by glass fragments of his own spectacles shattered while he was protecting an unknown woman from physical assault at a bus stop. Over a span of 65 months the patient underwent multiple procedures including primary wound repair, penetrating keratoplasty combined with extracapsular cataract extraction, neodymium: YAG laser capsulotomy, and laser-assisted subepithelial keratectomy (LASEK), and had a successfully treated episode of corneal graft rejection. This sequence of treatment substantially improved his left eye vision from hand movements at the time of admission to 0.9-0.5 × 90 at the last follow-up nearly 10 years after the trauma. Proper initial surgical management of an open globe injury can create the possibility for virtually complete vision restoration.

Conformational analysis of flephedrone using quantum mechanical models.

Flephedrone is an analogue of cathinone - chemically similar to ephedrine, cathine and other amphetamines. Conformations of all isomers of flephedrone have been studied at the quantum-chemical level. Calculations have been performed using DFT and MP2 methods with two basis sets - 6-31G and 6-31G(d,p). Results show that there are low energy conformers for the ortho, meta, and para isomers that are connected by way of low-barrier transition states. Boltzmann distribution of population predicts the highest population for the 1-meta conformer with a 10% increase in solution. The molecular electrostatic potential surface data for each molecule has been calculated revealing likely reaction sites.

A retrospective analysis of the intraocular lens power calculation in cases of sulcus fixation.

PURPOSE: To evaluate the refractive results in patients with intraocular lenses fixated in the sulcus of posterior chamber. Sulcus fixation causes a more anterior position of IOL than had been intended during the preoperative power calculation. A lack of correction of the IOL's power results in a myopic shift. MATERIAL AND METHODS: 27 patients (27 eyes) who underwent cataract surgery by phacoemulsification and foldable IOL MA60BM sulcus fixation due to a posterior capsule rupture at the Department of Ophthalmology, Medical University of Warsaw. The position of the IOL was confirmed by ultrabiomicroscopy. The study included patients with axial lengths ranging from 22 to 25 mm. Patients who suffered from a corneal astigmatism of > 1,00 Dcyl prior to the surgery were excluded from the study. The study also excluded patients with vitreous loss as this causes the anterior chamber to become deeper after vitrectomy, and consequently the IOL might sit in a more posterior position. The difference between the predicted and the postoperative refraction was evaluated. RESULTS: The mean visual acuity was significantly better after cataract surgery. The best corrected visual acuity (BCVA) was 1.0, which occurred in 19 cases (70%). The myopic shift, which was assessed as a mean difference between the predicted and the postoperative refraction after sulcus fixation, was 1.25 D. CONCLUSIONS: In order to avoid a myopic shift in the case of sulcus fixation, the IOL power calculation should be adjusted accordingly. The authors recommend that the IOL power should be reduced by approximately 1.25 to 1.50 D in emetropic eyes.

Comparison of the biometric measurements obtained using noncontact optical biometers LenStar LS 900 and IOL Master V.5.

PURPOSE: Evaluation of the measurement accuracy using a new optical biometer LenStar LS 900 (Haag Strait) and comparison according to the IOL Master V.5 (Zeiss) device. METHODS: In a prospective clinical study biometric measurements along with artificial lens power calculation using the LenStar LS 900 device were performed. A total number of 106 patients qualified for a cataract extraction procedure were included in the study. Measurements along with lens power calculation were repeated using the IOL Master V.5. device. Results were elaborated using Pearson's correlation and Bland-Altman plot. RESULTS: Measurements were performed in 204 eyes of 106 patients. Mean values and ranges of biometry results were as follows: 23.46 +/- 2.81 mm [20.79-29.80] for IOL Master, and 23.47 +/- 2.83 mm [20.79-29.86] for LenStar LS 900. In keratometry for flat meridian (K1) the following data was obtained: mean 43.24 +/- 3.22 D [range 38.27-47.94] for IOL Master and 42.44 +/- 3.15 D [38.27-47.94] for LenStar LS 900. For steep meridian (K2) the data obtained were 44.14 +/- 3.40 D; [39.29-49.13] and 43.27 +/- 3.34 D [38.61-48.4] respectively. The obtained calculation results for each eye were as follows: mean 21.23 +/- 8.07, [range 3.25-28.99] for Hagis formula, 21.14 +/- 6.90; [4.83-27.6] for SRK II, 21.04 +/- 7.78; [3.05-28.05] for SRK/T, 21.09 +/- 8.13; [2.43-28.61] for Holladay using IOL Master and 21.41 +/- 8.23; [2.99-29.15] for Haigis; 21.24 +/- 7.00; [4.6-27.71] for SRK II, 21.13 +/- 7.90; [2.76-28.18] for SRK/T; 21.09 +/- 8.13; [2.16-28.76] for Holladay using LenStar LS 900. CONCLUSIONS: The LenStar LS 900 device enables to perform accurate and repetitive biometric measurements and implant power calculations. Implant calculation results obtained using the LenStar LS 900 device are comparable to those achieved using the IOL Master V.5 device, which has been commonly accepted as standard for over a decade. The use of both devices is limited by significant lens opacification and posterior capsule calcification. In such cases, additional ultrasound biometry should be performed. Keratometry results obtained using both devices should not be used alternatively because of the different measurement methods and different refraction indexes. The LenStar LS 900 device comparing to the IOL Master additionally enables pachymetry, macular retinal thickness, lens thickens and pupil diameter measurement. Accuracy of those measurements should be studied in the future.

[Posterior polymorphous dystrophy--changes in corneal morphology in confocal microscopy]. / Dystrofia polimorficzna tylna--zmiany w morfologii rogówki obserwowane z uzyciem mikroskopii konfokalnej.

PURPOSE: To describe the in vivo conocal microscopic findings in posterior polymorphous dystrophy (PPD). MATERIAL AND METHODS: Eleven patients (22 eyes) with PPD suspected or clinically diagnosed were examined using scanning slit white light confocal microscopy (ConfoScan 3, Nidek Technologies). RESULTS: Endothelial cell densities ranged from 716 to 2380 cells/mm2 and endothelial polymegathism was noted in all cases. In 5 cases PPD changes was reported unilateral. Confocal microscopy demonstrated a variety of vesicular and linear abnormalities. In 13 eyes exhibited bright, nucleus-like structures within endothelial cells. Stromal edema was noted in 4 cases. CONCLUSIONS: To our knowledge, we present the largest case series of PPD imaged by in vivo confocal microscopy. Confocal microscopy images of PPD are very characteristic. This method allows to confirm presumptive or to identify final diagnosis. Our study enhances the value of confocal microscopy in detection and monitoring corneal abnormalities.

[Intraocular lens power calculation in patients after keratorefractive surgery--personal experience]. / Kalkulacja mocy implantów soczewek wewnatrzgalkowych u pacjentów po chirurgii refrakcyjnej rogówki--doswiadczenia wlasne.

PURPOSE: To assess the efficacy of intraocular lens power calculation in patients with previous corneal refractive surgery. MATERIAL AND METHODS: Retrospective analysis of patients after laser refractive procedures, in whom cataract removal with phacoemulsification method was performed. Corneal power, which in conventional measurements after refractive surgery tends to increase value and results in postoperative hyperopic shift, were calculated with five methods, and the results were compared. To asses IOL power SRK/T formula was used. RESULTS: Mean spherical equivalent three months after procedures according to target refraction in examined patients ranged from -1.00 to +1.75 D. The difference between obtained and target refraction in 55% of patients ranged from -0.50 to +0.50, and in 77% from -0.75D to +0.75D. Best results were obtained in calculations performed with Rossa method. The least effective appeared to be traditional IOL power calculation method without correcting factors. CONCLUSIONS: In patients after laser correction of myopia, value of the measured keratometry should always be corrected. The most effective is Rosa method in combination with SRK/T calculation algorithm.

[Evaluation of the usefulness of corneal scanning topography performed with Orbscan for the localization of corneal transplantation due to keratoconus]. / Ocena przydatnosci skaningowej topografii optycznej rogówki wykonanej aparatem Orbscan II do lokalizacji i okreslenia srednicy przeszczepu w stozku rogówki--doniesienie wstepne.

PURPOSE: Evaluation of the usefulness of corneal scanning topography performed with Orbscan for the localization of corneal graft due to keratoconus. MATERIAL AND METHODS: We examined 33 eyes in 33 individuals (23 men 10 women) during one year 2000/2001. Corneal topography was performed with Orbscan apparatus before the transplantation of the cornea due to the keratoconus. Trepanning depended of the thickness of peripheral cornea. Visual acuity without correction was compared with the control group of 33 eyes, after corneal transplantation done due to the corneal cone between 1998-1999, without consideration of scanning topography. RESULTS: Significant differences in the post-surgical visual acuity in favor of the examined group in the range from 5/5 to 5/7 and from 5/25 to 5/50 were observed. CONCLUSIONS: Scanning corneal topography will probably facilitate proper qualification for the transplantation and better postoperative visual acuity.

[Posterior polymorphous corneal dystrophy--diagnostic difficulties]. / Dystrofia polimorficzna tylna rogówki--trudnosci diagnostyczne.

PURPOSE: This paper describes complications due to the posterior polymorphous corneal dystrophy in one patient. MATERIAL AND METHODS: Medical history of misdiagnosis and subsequent wrong procedures, to which patient with binocular posterior polymorphous corneal dystrophy was exposed, where presented. The eye misdiagnosed with profound keratitis was initially treated with high doses of steroids, what could possibly lead to extensive fungal corneal ulceration and complicated cataract. RESULTS: Thanks to the detailed examination of the fellow eye in the slit lamp and specular microscope, correct diagnosis was made. CONCLUSIONS: Since posterior polymorphous corneal dystrophy is one of the rare conditions, especially with coexisting eye irritation, wrong diagnosis of this disorder is possible to be made. Therefore, extremely important in every day ophthalmological practice precise examination of the both eyes and special care during steroid treatment is essential.