Probing the supramolecular features via π–π interaction of a di-iminopyrene-di-benzo-18-crown-6-ether compound: experimental and theoretical study

A novel DPyDB-C N-18C6 compound was synthesised by linking a pyrene moiety to each phenyl group of dibenzo-18-crown-6-ether, the crown ether, through –HC N– bonds and characterized by FTIR, ¹H-NMR, ¹³C-NMR, TGA, and DSC techniques. The quantitative ¹³C-NMR analysis revealed the presence of two position isomers. The electronic structure of the DPyDB-C N-18C6 molecule was characterized by UV-vis and fluorescence spectroscopies in four solvents with different polarities to observe particular behavior of isomers, as well as to demonstrate a possible non-bonding chemical association (such as ground- and excited-state associations, namely, to probe if there were forming dimers/excimers). The interpretation of the electronic structure was realized through QM calculations. The TD-CAM-B3LYP functional, at the 6-311+G(d,p) basis set, indicated the presence of predominant π → π* and mixed π → π* + n → π* transitions, in line with the UV-vis experimental data. Even though DPyDB-C N-18C6 computational studies revealed a π-extended conjugation effect with predominantly π → π* transitions, thorough fluorescence analysis was observed a weak emission, as an effect of PET and ACQ. In particular, the WAXD analysis of powder and thin films obtained from n-hexane, 1,2-dichloroethane, and ethanol indicated an amorphous organization, whereas from toluene a smectic ordering was obtained. These results were correlated with MD simulation, and it was observed that the molecular geometry of DPyDB-C N-18C6 molecule played a defining role in the pyrene stacking arrangement.

Herein, we report the formation of a potential supramolecular arrangement mediated by inter- and intra-molecular interactions between di-iminopyrene-dibenzo-18-crown-6-ether molecules.     

Thermal, dynamic mechanical, and dielectric analyses of some polyurethane biocomposites

Polymer biocomposites based on segmented poly(ester urethane) and extracellular matrix components have been prepared for the development of tissue engineering applications with improved biological characteristics of the materials in contact with blood and tissues for long periods. Thermal, dynamical, and dielectrical analyses were employed to study the molecular dynamics of these materials and the influence of changing the physical network morphology and hydrogen bond interactions accompanied by phase transitions, interfacial effects, and polarization or conductivity. All phenomena that concur in the tested materials are evaluated by cross-examination of the dynamic mechanical characteristic properties (storage modulus, loss modulus, and loss factor) and dielectric properties (relative permittivity, relative loss factor, and loss tangent) as a function of temperature. Comparative aspects were elucidated by calculating the apparent activation energies of multiplex experiments.     

HIV gp120 H375 is unique to HIV-1 subtype CRF01_AE and confers strong resistance to the entry inhibitor BMS-599793, a candidate microbicide drug

BMS-599793 is a small molecule entry inhibitor that binds to human immunodeficiency virus type 1 (HIV-1) gp120, resulting in the inhibition of CD4-dependent entry into cells. Since BMS-599793 is currently considered a candidate microbicide drug, we evaluated its efficacy against a number of primary patient HIV isolates from different subtypes and circulating recombinant forms (CRFs) and showed that activity varied between ～3 ρM and 7 μM at 50% effective concentrations (EC(50)s). Interestingly, CRF01_AE HIV-1 isolates consistently demonstrated natural resistance against this compound. Genotypic analysis of >1,600 sequences (Los Alamos HIV sequence database) indicated that a single amino acid polymorphism in Env, H375, may account for the observed BMS-599793 resistance in CRF01_AE HIV-1. Results of site-directed mutagenesis experiments confirmed this hypothesis, and in silico drug docking simulations identified a drug resistance mechanism at the molecular level. In addition, CRF01_AE viruses were shown to be resistant to multiple broadly neutralizing monoclonal antibodies. Thus, our results not only provide insight into how Env polymorphisms may contribute to entry inhibitor resistance but also may help to elucidate how HIV can evade some broadly neutralizing antibodies. Furthermore, the high frequency of H375 in CRF01_AE HIV-1, and its apparent nonoccurrence in other subtypes, could serve as a means for rapid identification of CRF01_AE infections.     

The Role of Phylogenetics in Unravelling Patterns of HIV Transmission towards Epidemic Control: The Quebec Experience (2002–2020)

Phylogenetics has been advanced as a structural framework to infer evolving trends in the regional spread of HIV-1 and guide public health interventions. In Quebec, molecular network analyses tracked HIV transmission dynamics from 2002–2020 using MEGA10-Neighbour-joining, HIV-TRACE, and MicrobeTrace methodologies. Phylogenetics revealed three patterns of viral spread among Men having Sex with Men (MSM, n = 5024) and heterosexuals (HET, n = 1345) harbouring subtype B epidemics as well as B and non-B subtype epidemics (n = 1848) introduced through migration. Notably, half of new subtype B infections amongst MSM and HET segregating as solitary transmissions or small cluster networks (2–5 members) declined by 70% from 2006–2020, concomitant to advances in treatment-as-prevention. Nonetheless, subtype B epidemic control amongst MSM was thwarted by the ongoing genesis and expansion of super-spreader large cluster variants leading to micro-epidemics, averaging 49 members/cluster at the end of 2020. The growth of large clusters was related to forward transmission cascades of untreated early-stage infections, younger at-risk populations, more transmissible/replicative-competent strains, and changing demographics. Subtype B and non-B subtype infections introduced through recent migration now surpass the domestic epidemic amongst MSM. Phylodynamics can assist in predicting and responding to active, recurrent, and newly emergent large cluster networks, as well as the cryptic spread of HIV introduced through migration.     

Phylogenetic Clustering among Asylum Seekers with New HIV-1 Diagnoses in Montreal,QC, Canada

Migrants are at an increased risk of HIV acquisition. We aimed to use phylogenetics to characterize transmission clusters among newly-diagnosed asylum seekers and to understand the role of networks in local HIV transmission. Retrospective chart reviews of asylum seekers linked to HIV care between 1 June 2017 and 31 December 2018 at the McGill University Health Centre and the Jewish General Hospital in Montreal were performed. HIV-1 partial pol sequences were analyzed among study participants and individuals in the provincial genotyping database. Trees were reconstructed using MEGA10 neighbor-joining analysis. Clustering of linked viral sequences was based on a strong bootstrap support (>97%) and a short genetic distance (<0.01). Overall, 10,645 provincial sequences and 105 asylum seekers were included. A total of 13/105 participant sequences (12%; n = 7 males) formed part of eight clusters. Four clusters (two to three people) included only study participants (n = 9) and four clusters (two to three people) included four study participants clustered with six individuals from the provincial genotyping database. Six (75%) clusters were HIV subtype B. We identified the presence of HIV-1 phylogenetic clusters among asylum seekers and at a population-level. Our findings highlight the complementary role of cohort data and population-level genotypic surveillance to better characterize transmission clusters in Quebec.