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Zeead AlGhamdi,1 Shaya Y Alqahtani,2 Khalid AlDajani,1 Ammar Alsaedi,1 Omar Al-Rubaish,1 Abdulmajeed Alharbi,1 Hatem Elbawab1 1Thoracic Surgery Division, Department of Surgery, College of medicine, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia; 2Department of Internal Medicine and Critical Care Medicine, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam, Saudi ArabiaCorrespondence: Zeead AlGhamdi, Thoracic surgery division, Department of Surgery, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia, Tel +966504845350, Email zghamdi@iau.edu.saBackground: Previous studies have been conducted to assess pneumothorax. However, few studies were done to assess pneumothorax in COVID-19 patients in the intensive care unit (ICU).Objective: Our aim is to describe and analyze the prevalence, clinical characteristics, risk factors, and outcomes of COVID-19 pneumothorax patients in the intensive care unit.Methods: We performed a retrospective review of the medical records of 418 patients, who tested positive for COVID-19 by polymerase chain reaction test and required ICU admission in King Fahad Hospital of The University from 02/01/2020 to 01/09/2021. A total number of 36 pneumothorax patients were included in the study.Results: Of 418 patients who were followed up in the intensive care unit as COVID-19 cases, 36 patients developed a pneumothorax (8.61%). The mean age of the patients was 55.6 ± 15.06 years, 23 patients were male, and 13 were female. Seventeen patients were obese, and only one patient was an active smoker. Twenty-four patients had at least one comorbidity; hypertension was the most common. Thirty-two patients were intubated, and the duration of intubation was 23.23 ± 15.9 days. The time from intubation to pneumothorax development was 8.8 ± 9.3 days. Six patients were on bilevel positive airway pressure ventilation (BIPAP), 2 patients on continuous positive airway pressure ventilation (CPAP), 3 patients on High-Flow Nasal Cannula ventilation (HFNC), 9 patients on pressure-control ventilation (PC), and 16 patients on pressure regulated volume control ventilation (PRVC). Of 36 patients, 26 died, and the mortality rate was 72.2%.Conclusion: Our study showed that risk factors of pneumothorax occurrence in COVID-19 critically ill patients include male patients, hypertension, diabetes mellitus, endotracheal intubation and mechanical ventilation. More efforts should be made to determine the risk factors and assess the outcomes of those patients to develop preventive measures and management guidelines.Keywords: pneumothorax, COVID-19, intensive care unit, risk factors, outcomes

Background Coinfection at various sites can complicate the clinical course of coronavirus disease of 2019 (COVID-19) patients leading to worse prognosis and increased mortality. We aimed to investigate the occurrence of coinfection in critically ill COVID-19 cases, and the predictive role of routinely tested biomarkers on admission for mortality. Methods This is a retrospective study of all SARS-CoV-2-infected cases, who were admitted to King Fahad Hospital of the University between March 2020 and December 2020. We reviewed the data in the electronic charts in the healthcare information management system including initial presentation, clinical course, radiological and laboratory findings and reported all significant microbiological cultures that indicated antimicrobial therapy. The mortality data were reviewed for severely ill patients who were admitted to critical care units. Results Of 1091 admitted patients, there were 70 fatalities (6.4%). 182 COVID-19 persons were admitted to the critical care service, of whom 114 patients (62.6%) survived. The in-hospital mortality was 13.4%. Coinfection was noted in 67/68 non-survivors, and Gram-negative pathogens (Enterobacterales, Pseudomonas aeruginosa, and Acinetobacter baumanni) represented more than 50% of the etiological agents. We noted that the serum procalcitonin on admission was higher for non-survivors (Median = 1.6 ng/mL ± 4.7) than in survivors (Median = 0.2 ng/mL ± 4.2) (p ≤ 0.05). Conclusion Coinfection is a serious complication for COVID-19 especially in the presence of co-morbidities. High levels of procalcitonin on admission may predict non-survival in critically ill cases in whom bacterial or fungal co-infection is likely.

Photodynamic therapy (PDT) has drawn a great scientific attention to cancer treatment over the last decades. However, the bottleneck for the PDT is to find good photosensitizers (PSs) with greater water solubility, no aggregation, and fast discharge from the body. Therefore, there are still a big scientific desire for the synthesizing new rational PSs for treatment of cancer by PDT technique. In favor of improving the competence of PDT, an axially bis[4-(diphenylamino-1,1′-biphenyl-4-ol)] substituted silicon(IV) phthalocyanine (3) was converted to its water-soluble quaternized derivative (3Q). Their structures were fully characterized by single-crystal X-ray diffraction, elemental analysis, and different spectroscopic methods such as FT-IR, UV–Vis, MALDI-TOF, and 1H-NMR. The photophysical properties such as fluorescence quantum yields and lifetimes, and the photochemical properties such as singlet oxygen generation of both phthalocyanines were investigated. Ground and excited-state calculations were performed to explain the observed electronic absorption spectra. The addition of the 4-diphenylamino-1,1′-biphenyl-4-ol groups on the axially positions of the silicon(IV) phthalocyanine increased the singlet oxygen quantum yield from 0.15 to around 0.20. Especially quaternized compound 3Q showed high singlet oxygen quantum yield of 0.26 in water solution. In addition, a spectroscopic investigation of the binding behavior of the quaternized silicon (IV) phthalocyanine complex to bovine serum albumin (BSA) is also studied in this work, confirming the possible interaction. Further theoretical calculations were carried out to find out the plausible-binding regions of the BSA protein.

Afnan J Alshrefy,1 Rawaa N Alwohaibi,1 Shahad A Alhazzaa,1 Reema A Almaimoni,1 Latifah I AlMusailet,1 Shaya Y AlQahtani,2 Mohammed S Alshahrani3 1College of Medicine, Imam Abdulrahman bin Faisal University, Dammam, Eastern Province, Saudi Arabia; 2Department of Internal Medicine and Critical Care Medicine, King Fahd Hospital of the University, Imam Abdulrahman bin Faisal University, Khobar, Eastern Province, Saudi Arabia; 3Emergency and Critical Care Departments, King Fahd Hospital of the University, Imam Abdulrahman bin Faisal University, Khobar, Eastern Province, Saudi ArabiaCorrespondence: Mohammed S Alshahrani, Emergency and Critical Care Departments, King Fahd Hospital of the University, Imam Abdulrahman bin Faisal University, Khobar, Eastern Province, 34219, Saudi Arabia, Tel +966556966663, Fax +966138966770, Email Msshahrani@iau.edu.saPurpose: Secondary infections have been observed among coronavirus disease 2019 (COVID-19) patients, especially in the intensive care unit (ICU) setting, which is associated with worse clinical outcomes. The current study aimed to investigate the incidence, common pathogens, and outcome of bacterial and fungal secondary infections among ICU patients with COVID-19.Methods: A retrospective chart review of all patients admitted to the ICU at King Fahd Hospital of the University in Saudi Arabia. All adult patients aged ≥ 18 admitted in the ICU for ≥ 48 hours with positive COVID-19 reverse transcription-polymerase chain reaction test during the period between March 2020 till September 2021 were included.Results: Out of 314 critically ill patients, 133 (42.4%) developed secondary infections. The incidence of secondary bacterial infection was 32.5% with Pseudomonas aeruginosa (n = 34), Acinetobacter baumannii (n = 33), and Klebsiella pneumoniae (n = 17) being the predominant pathogens, while secondary fungal infection was 25.2% mainly caused by Candida albicans (n = 43). Invasive mechanical ventilation was significantly associated with the development of secondary bacterial infections (odds ratio [OR] = 17.702, 95% confidence interval [CI] 7.842– 39.961, p < 0.001) and secondary fungal infections (OR = 12.914, 95% CI 5.406– 30.849, p < 0.001). Mortality among patients with secondary infections was 69.2% (n = 92). Secondary infections were associated with longer hospital and ICU stays with a median of 25 days (interquartile range [IQR] 17– 42) and 19 days (IQR 13– 32), respectively.Conclusion: Bacterial and fungal secondary infections are common among COVID-19 patients admitted to the ICU with a predominance of gram-negative bacteria and Candida species. The development of secondary infections was significantly associated with invasive mechanical ventilation. Poor clinical outcomes have been observed, demonstrated with a prolonged hospital and ICU stays and higher mortality.Keywords: COVID-19, intensive care unit, secondary infection, bacterial, fungal

Twelve novel chalcones were synthesized using 2-alkyloxy-naphthaldehydes and Mannich bases of 4-hydroxyacetophenone. The chalcones were characterized using FTIR, 1D and 2D NMR and HRMS spectroscopy. Comparative docking analysis was carried out to screen their affinity towards the AChE enzyme (PDB 1EVE). All chalcones showed lower binding energy (−13.06 to −10.43 kcal/mol) against AChE better than donepezil (−10.52 kcal/mol). All chalcones were potent inhibitors towards AChE, with IC50 values ranging between 0.11 and 5.34 nM better than donepezil (IC50 33.4 nM) and selectivity indexes (0.66–23.83), despite the fact that chalcones 10 and 13 were inactive. The structure activity relationship indicated that introducing diethyl amine in ring A of the chalcone skeleton and the propargyl moiety at ring B was affirmed to be a prospective drug against AChE. The multifunctional properties of chalcone 15 were all advantages that demonstrate an excellent candidate for the development of an effective drug against AChE.

The design of an acetylcholinesterase inhibitor with multifunctional properties became the perspective for the development of an effective drug against Alzheimer's disease. Towards this target, 1-{4-hydroxy-3-[(piperidin-1-yl)methyl]phenyl}ethan-1-one (chalcone 3) was prepared and studied as an acetylcholinesterase inhibitor. The novel chalcone 3 was synthesised via Claisen-Schmidt condensation reaction with 84% yield and characterized using 1D and 2D NMR spectroscopy. The in vitro bioactivity studies of chalcone 3 demonstrated excellent inhibitory activity against AChE (IC50 1.0 nM) showing 33-fold better inhibition than donepezil, biometal chelating ability and moderate antioxidant activity. Chalcone 3 with these fascinating multifunctional proprieties can be a good candidate for the development of AD treatments. A molecular modelling investigation revealed that chalcone 3 showed dual binding inhibition of AChE enzyme. XRD shows short intra- and inter-molecular interactions with two chalcone 3 molecules per cell. Interesting Hirshfeld Surface Analysis (HSA) was conducted showing explicit agreement with the XRD analysis.

This article is focused on the design and photophysical properties of a series of novel porphyrin and metalloporphyrin dendrimers containing cationic η6-chloroarene-η5-cyclopentadienyliron(II) complexes functionalized with naphthalene and capped with ferrocene. The incorporation of cationic η6-chloroarene-η5-cyclopentadienyliron moieties into the dendrimer structures enhances solubility, and facilitates nucleophilic aromatic substitution and addition reactions due to the intense electron-withdrawing ability of the iron center. Divergent approaches were employed to yield highly symmetrical branched materials, with interesting and potentially useful properties. The preparation of these dendrimers was achieved via metal-mediated nucleophilic aromatic substitutions and Steglich esterifications. These dendrimers and their precursors were characterized through nuclear magnetic resonance spectroscopy, infrared spectroscopy, and UV–Visible and fluorescence spectroscopy. Substitution on the porphyrin core with various side chains and terminal functional groups and chromophores had little impact on the porphyrin emission properties, allowing for a wide variety of fluorescent macromolecules to be prepared which retain this characteristic emission. Also, the presence or absence of the organopyrene moieties also had little effect on the emission from these compounds. Complexation of a metal cation, such as Zn2+, by these compounds, did however result in a significant blue shift in the observed fluorescence; this interesting result has the potential for applications in the development of fluorescent-based cation sensors.

In this study, the novel 4-(N,N′-dimethylamino)phenyl substituted lutetium(III) acetate phthalocyanine (2) and its quaternized derivative (3) were synthesized via a Suzuki-Miyaura coupling reaction between tetrakis(iodo) lutetium(III)acetate phthalocyanine (1) and 4-(N,N-dimethylamino)phenylboronic acid, and subsequent quaternization using dimethyl sulfate, respectively. The obtained phthalocyanine 3 exhibited excellent solubility in water which is important for photodynamic therapy applications. Photophysical properties such as fluorescence quantum yield and fluorescence lifetime, and photochemical properties such as singlet oxygen generation and photostability were investigated to determine their suitability for photodynamic therapy. The lutetium(III) phthalocyanines, especially quaternized derivative 3, showed promising properties as potential photosensitizers for the treatment of cancer, producing higher singlet oxygen (ΦΔ = 0.59) than motexafin lutetium (ΦΔ = 0.31) which is a clinically used lutetium texaphyrin photosensitizer.

Phenyl-4,4-di(3,6-dibutoxyphthalonitrile) ( 3 ) was synthesized by the reaction of 1,4-phenylenebisboronic acid ( 1 ) and 4-bromo-3,6-dibutoxyphthalonitrile ( 2 ), using Suzuki cross-coupling reaction. The newly synthesized compound ( 3 ) was characterized by FT-IR, MALDI-MS, ESI-MS, 1 H-NMR, 13 C-NMR, and 13 C-DEPT-135-NMR. The fluorescence property of phenyl-4,4-di(3,6-dibutoxyphthalonitrile) ( 3 ) towards various metal ions was investigated by fluorescence spectroscopy, and it was observed thatthe compound ( 3 ) displayed a significantly ‘turn-off’ response to Fe 3+ , which was referred to 1:2 complex formation between ligand ( 3 ) and Fe 3+ . The compound was also studied via density functional theory calculations revealing the interaction mechanism of the molecule with Fe 3+ ions.

In an attempt to design and prepare a new library of anticancer candidates, focused thiopropargylated benzothiazole was reacted with ethyl azidoacetate and/or ethyl azidobenzoate to yield newer 1,2,3-triazole-benzothiazole conjugates bearing ester functionality through click chemistry approach. The hydrazinolysis of the obtained ester-based triazoles was also carried out to give the corresponding 1,2,3-triazole acid hydrazide derivatives as precursors for the synthesis of the focused Schiff bases by their condensation with various benzaldehyde derivatives. Spectroscopic study was investigated on the establishment of the structures of all newly synthesized Schiff bases bearing benzothiazole-1,2,3-triazole molecular conjugate. The newly designed hydrazones showed two isomers (cis-E and trans-E) with different isomeric distribution as confirmed by NMR spectral data and supported by DFT carried out in gas phase at B3LYP 6‒311G (d,p) basis set. The DFT results showed that the cis-E isomer is the lower energy structure and this finding was illustrated in terms of the intermolecular H-bonding. These molecules were screened for anticancer activities with A549 and H1299 lung cancer cell lines. The anticancer activities ranged from 55 to 90%. DNA binding study was also carried out to see the mechanism of action and the DNA binding constants were of good value ranging from of 2.0 × 105 and 14.7 × 105 M−1; indicating good interactions of the reported molecules with DNA. Finally, the modeling was confirmed and it was found that the results of modeling were in good agreement with the results of anticancer and DNA binding studies. All these finding confirmed that the reported molecules work as anticancer agents by interacting with DNA.

Despite the availability of some drugs, there is an urgent need for effective anti-cancer medication. It is due to various side effects and non-functionality of the present drugs; especially at the late stage of cancer. Therefore, three series (4a-e, 6a-e and 8a-j; 21 compounds) of benzotriazole-1,2,3-triazole hybrids (carrying different pharmacophores) have been designed and synthesized (by both conventional and microwave syntheses) through the Cu(I)-catalyzed click 1,3-dipolar cycloaddition reaction of the propargylated benzotriazole with the appropriate aliphatic, aromatic and phenyl/benzyl acetamide azides. The syntheses times were from 6 to 12 h and 4 to 8 min in conventional and microwave syntheses. The yields were 80 to 86% and 89 to 95% in conventional and microwave syntheses; confirming microwave synthesis as an economic and eco-friendly method. These compounds were characterized by proper spectroscopic methods. The anticancer activities with A549 and H1299 lung cancer cell lines were in the range of 70.0 to 90.0% for 4a-e series, 78.0 to 90.0% for 6a-e series and 81.0 to 90.0% for 8a-j series. The reported compounds showed good DNA binding constants in the range of 1.3 × 103 to 11.90 × 105 M−1. The docking results suggested strong DNA bindings of the reported compounds in the minor grooves of DNA; through hydrogen bonding and hydrophobic interactions. The quite good anticancer activities and high DNA binding constants have indicated that the reported molecules may be future anticancer agents.

The novel zinc(II) phthalocyanine directly conjugated with 4-(diethylamino)phenyl groups (2) via C C bond formation using Suzuki-Miyaura coupling reaction was synthesized for the first time. This phthalocyanine was converted to the quaternized derivative (3) to enhance its water solubility. The photochemical (singlet oxygen quantum yield and photodegradation quantum yield) and photophysical (fluorescence quantum yield and lifetime) properties of the synthesized novel zinc(II) phthalocyanines (2 and 3) were investigated in DMSO (for both phthalocyanines 2 and 3) and in aqueous solution (for only phthalocyanine 3) for determination of their photodynamic therapy abilities. Additionally, the bovine serum albumin (BSA) binding behavior of the water soluble zinc(II) phthalocyanine (3) was investigated in aqueous solution for determination of transporting capability of this phthalocyanine in the circulatory system.

The symmetrical zinc(II) phthalocyanines conjugated with 9,10-dioctyl-6,7-dimethoxy-2,3-dioxytriptycene or 9,10-diundecyl-6,7-dimethoxy-2,3-dioxytriptycene moieties were synthesized in this study. These novel phthalocyanines were characterized by standard characterization techniques such as 1H-NMR, FT-IR, UV–vis, Mass and Elemental Analysis. All these phthalocyanines showed highly solubility and formed non-aggregated monomeric species in most of the organic solvents. Their photochemical properties such as singlet oxygen, and photodegradation quantum yields, and photophysical properties including fluorescence quantum yields and lifetimes were investigated in toluene. The fluorescence quenching behavior of the studied zinc(II) phthalocyanines by the addition of 1,4-benzoquinone were also described in toluene.

The novel axially bis[4-(4-pyridinyl)phenol] substituted silicon(IV) phthalocyanine (3) and its quaternized derivative (3Q) were designed and synthesized. These phthalocyanines were fully characterized by elemental analysis and different spectroscopic methods, such as FT-IR, UV–Vis, MALDI-TOF and 1H NMR. The photophysical and photochemical properties, such as electronic absorption, fluorescence emission, fluorescence lifetimes, singlet oxygen generation and photostability, of these phthalocyanines were investigated. These properties were examined in DMSO for the non-ionic phthalocyanine (3) and in both DMSO and aqueous solution for the ionic phthalocyanine (3Q). The addition of bis[4-(4-pyridinyl)phenol] groups as axial ligands showed an improvement of the photophysical and photochemical properties. In addition, a spectroscopic investigation of the binding behavior of the quaternized silicon(IV) phthalocyanine complex to bovine serum albumin (BSA) and DNA was also studied in this work.

The syntheses of a novel 1,4,8,11,15,18,22,25-octahexyloxy-2,3,9,10,16,17,23,24-octa-(4-trifluoromethoxyphenyl) phthalocyanine (3a) and its zinc(II) phthalocyanine derivative (3b) have been described and characterized by elemental analysis,1H NMR, 13C NMR, 19F NMR, mass, UV-Vis and FT-IR. The newly prepared metal-free phthalocyanine and its zinc(II) counterpart are soluble in most organic solvents. The photophysical and photochemical properties such as aggregation, fluorescence, singlet oxygen generation and photodegradation under light irradiation of these phthalocyanines have been investigated in DMF. The hexadeca-substituted phthalocyanines (3a and 3b) showed longer absorption and emission wavelength values when compared to that of reported phthalocyanine derivatives due to substitution of the all possible positions in the phthalocyanine framework. The zinc(II) phthalocyanine derivative does not only have a good singlet oxygen generation but also has other photophysicochemical properties that enables this phthalocyanine to be useful as a photosensitizer for cancer treatment using photodynamic therapy.

The syntheses of a novel 1,4,8,11,15,18,22,25-octahexyloxy-2,3,9,10,16,17,23,24-octa-(4-trifluoromethoxyphenyl) phthalocyanine (3a) and its zinc(II) phthalocyanine derivative (3b) have been described and characterized by elemental analysis,1H NMR, 13C NMR, 19F NMR, mass, UV-Vis and FT-IR. The newly prepared metal-free phthalocyanine and its zinc(II) counterpart are soluble in most organic solvents. The photophysical and photochemical properties such as aggregation, fluorescence, singlet oxygen generation and photodegradation under light irradiation of these phthalocyanines have been investigated in DMF. The hexadeca-substituted phthalocyanines (3a and 3b) showed longer absorption and emission wavelength values when compared to that of reported phthalocyanine derivatives due to substitution of the all possible positions in the phthalocyanine framework. The zinc(II) phthalocyanine derivative does not only have a good singlet oxygen generation but also has other photophysicochemical properties that enables this phthalocyanine to be useful as a photosensitizer for cancer treatment using photodynamic therapy.

C14H10O2, triclinic, P1̄ (no. 2), a = 7.498(3) Å, b = 7.973(3) Å, c = 9.660(4) Å, α = 67.211(13)°, β = 84.489(14)°, γ = 72.224(14)°, V = 506.8(4) Å3, Z = 2, Rgt(F) = 0.0394, wR ref(F 2) = 0.1135, T = 100(2) K.

A3B type unsymmetrical 8,11,15,18,22,25-hexadecyl-2,3-(9,10-dioctyl-6,7-dimethoxy-2,3-dioxytriptycene) (11) and 8,11,15,18,22,25-hexadecyl-2,3-(9,10-diundecyl-6,7-dimethoxy-2,3-dioxytriptycene) (12) zinc(II) phthalocyanines were synthesized for the first time. Their photophysical and photochemical properties were investigated as solutions in toluene and obtained values were compared with unsubstituted zinc(II) phthalocyanine for determination of substitution effect. Both newly synthesized phthalocyanines showed high singlet oxygen generation making them good candidates as photosensitizers for photocatalytic reactions.

New metal-free and zinc(II) phthalocyanines containing four triptycene moieties were synthesized and characterized by 1H NMR, mass, IR, electronic spectroscopies and elemental analysis as well. The steady-state absorption spectra of the investigated compounds exhibited the main absorption bands in the visible region, at around 700 nm. The fluorescence spectra and quantum yields were recorded by steady-state emission measurements. The powerful nanosecond laser flash photolysis technique was employed to record the transient absorption spectra of the long-lived triplet states of the investigated compounds. The singlet oxygen generation and photodegradation properties of the target phthalocyanines under light irradiation were also investigated in tetrahydrofuran solution.