Syntheses, structural, photophysical and theoretical studies of heteroleptic cycloplatinated guanidinate(1-) complexes bearing acetylacetonate and picolinate ancillary ligands.

Cycloplatination of symmetrical N,N',N''-triarylguanidines, (ArNH)2C[double bond, length as m-dash]NAr with cis-[Pt(TFA)2(S(O)Me2)2] in toluene afforded cis-[Pt(TAG)(TFA)(S(O)Me2)] (TAG = triarylguanidinate(1-)-κC,κN; TFA = OC(O)CF3; 6-9) in 75-82% yields. The reactions of 6-9 and the previously known cis-[Pt(TAG)X(S(O)Me2)] (X = Cl (1) and TFA (2-5)) with acetylacetone (acacH) or 2-picolinic acid (picH) in the presence of a base afforded [Pt(TAG)(acac)] (acac = acetylacetonate-κ2O,O'; 10-18) and [Pt(TAG)(pic)] (pic = 2-picolinate-κN,κO; 19) in high yields. The new complexes were characterised by analytical, IR and multinuclear NMR spectroscopies. Further, molecular structures of 11, 12, 13·0.5 toluene and 14-19 were determined by single crystal X-ray diffraction. Absorption spectra of 10-19 in solution and their emission spectra in crystalline form were measured. Platinacycles 10-19 are bluish green light emitter in the crystalline form, and emit in the λPL = 488-529 nm range (11 and 13-19) while 12 emits at λPL = 570 nm. Unlike other platinacycles, the emission band of 12 is broad, red shifted, and this pattern is ascribed to the presence of an intermolecular N-H⋯Pt interaction involving the endocyclic amino unit of the six-membered [Pt(TAG)] ring and the Pt(ii) atom in the adjacent molecule in an asymmetric unit of the crystal lattice. Lifetime measurements were carried out for all platinacycles in crystalline form, which revealed lifetime in the order of nanoseconds. The origin of absorption and emission properties of 11, 15, 18 and 19 were studied by TD-DFT calculations.

Investigating the structure, bonding, and energy decomposition analysis of group 10 transition metal carbonyls with substituted terminal germanium chalcogenides [M(CO)3GeX] (M = Ni, Pd, and Pt; X = O, S, Se, and Te) complexes: insight from first-principles calculations.

CONTEXT: This research focused on the theoretical investigation of transition metal carbonyls [M(CO)4] coordinated with terminal germanium chalcogenides complexes [M(CO)3GeX], where M represents Ni, Pd, and Pt and X represents O, S, Se, and Te labeled 1-15. While the notable complexes M(CO)4 (where M = Ni, Pd, Pt) numbered 1, 6, and 11 are of significance, substituting one of the CO ligands in 1, 6, and 11 with a GeX ligand (where X = O, S, Se, or Te) result in substituted complexes (2-5, 7-10, and 11-15). Substituting of the CO ligand slightly alters these bond angles. Specifically, the ∠CMC bond angles for [Ni] complexes range from 111.9° to 112.2°, for [Pd] complexes from 111.4° to 111.7°, and for [Pt] complexes from 112.4° to 112.8°. These findings indicate a minor deviation from the tetrahedral geometry due to the influence of the new GeX ligand. Similarly, there is a slight change in the geometry of the metal complexes, where the ∠GeMC angles for [Ni] complexes are between 106.7° and 106.9°, for [Pd] complexes between 107.2° and 107.5°, and for [Pt] complexes between 105.9° and 106.4°. Comparing among the substituted GeX complexes, those containing GeTe exhibit a higher natural bond orbital (NBO) contribution from the Ge atom compared to the M atom. Consequently, based on the above observations, it can be inferred that GeX acts as an effective sigma donor in contrast to carbonyl compounds. Results of energy decomposition analysis (EDA) for the M-CO bond in 1, 6, and 11 and for the M-GeX bond in the other [M(CO)3(GeX)] complexes where M = Ni, Pd and Pt. The percentage contribution of ΔEelstat and ΔEorb shows a relatively identical behavior for all ligands in case of each metal complexes. METHODS: Density functional theory (DFT) calculations were conducted using the B3LYP/gen/6-31G*/LanL2DZ level of theory to examine transition metal carbonyls [M(CO)4] coordinated with terminal germanium chalcogenides complexes [M(CO)3GeX], where M represents Ni, Pd, and Pt, and X represents O, S, Se, and Te labeled 1-15 utilized through the use of Gaussian 09W and GaussView 6.0.16 software packages. Post-processing computational code such as multi-wave function was employed for results analysis and visualization.

Repurposing synthetic and natural derivatives induces apoptosis in an orthotopic glioma-induced xenograft model by modulating WNT/ß-catenin signaling.

BACKGROUND: Glioblastomas arise from multistep tumorigenesis of the glial cells. Despite the current state-of-art treatment, tumor recurrence is inevitable. Among the innovations blooming up against glioblastoma, drug repurposing could provide profound premises for treatment enhancement. While considering this strategy, the efficacy of the repurposed drugs as monotherapies were not up to par; hence, the focus has now shifted to investigate the multidrug combinations. AIM: To investigate the efficacy of a quadruple-combinatorial treatment comprising temozolomide along with chloroquine, naringenin, and phloroglucinol in an orthotopic glioma-induced xenograft model. METHODS: Antiproliferative effect of the drugs was assessed by immunostaining. The expression profiles of WNT/ß-catenin and apoptotic markers were evaluated by qRT-PCR, immunoblotting, and ELISA. Patterns of mitochondrial depolarization was determined by flow cytometry. TUNEL assay was performed to affirm apoptosis induction. In vivo drug detection study was carried out by ESI-Q-TOF MS analysis. RESULTS: The quadruple-drug treatment had significantly hampered glioma proliferation and had induced apoptosis by modulating the WNT/ß-catenin signaling. Interestingly, the induction of apoptosis was associated with mitochondrial depolarization. The quadruple-drug cocktail had breached the blood-brain barrier and was detected in the brain tissue and plasma samples. CONCLUSION: The quadruple-drug combination served as a promising adjuvant therapy to combat glioblastoma lethality in vivo and can be probed for translation from bench to bedside.

Study of Non-Covalent Interactions Present in the Tapinarof-Ethanol System with Special Emphasis on Hydrogen-Bonding Interactions.

In this study, the effect of non-covalent interaction in the tapinarof-EtOH systems is evaluated, particularly the hydrogen-bonding interaction using density functional theory in a gas phase. From the optimization results and the binding energy calculated thereafter, it is concluded that interaction in the employed system occurs between the O-H groups on tapinarof and the oxygen atom of EtOH molecules existing in the vicinity of the O-H group. These interactions were concluded to be those of the weak hydrogen bonds by carrying out the reduced gradient approach and QTAIM analysis, which are basically electron-density-based topological analyses. The charge localization between the donor-acceptor moieties was analyzed using the NBO analysis. Using the LED analysis, the binding energy between the tapinarof and EtOH was partitioned into different energy terms centered on a domain-based local pair natural orbital coupled cluster method. Thus, the electronic environment of the tapinarof-EtOH systems is evaluated.

A Green Approach to the Synthesis of α-Amino Phosphonate in Water Medium: Carbene Insertion into the N-H Bond by Cu(I) Catalyst.

Synthesis of amino phosphonates is more important owing to their significant applications in the biological systems. There are few methods already known in the literature to make these molecules; however, known methods have their own disadvantages. In this regard, synthesis of different kinds of amino phosphonates have been achieved via phosphonate substituted carbene insertion into the N-H bond of aniline catalyzed by readily available copper salt under mild reaction conditions in water. In order to find an efficient catalyst for carbene insertion reaction in neat water, a large number of transition metal catalysts were screened, and we found that the [Cu(CH3CN)4]ClO4 was the best catalyst under employed reaction conditions. Using this environmentally benign methodology (copper catalyzed reaction in water), a large number of biologically important amino phosphonates have been synthesized, isolated (37 examples), and characterized using standard analytical and spectroscopic techniques.