Duquesne University

About: Duquesne University is a education organization based out in Pittsburgh, Pennsylvania, United States. It is known for research contribution in the topics: Population & Health care. The organization has 3615 authors who have published 7169 publications receiving 180066 citations. The organization is also known as: Duquesne University of the Holy Spirit.

Synthesis of classical, three-carbon-bridged 5-substituted furo[2,3-d]pyrimidine and 6-substituted pyrrolo[2,3-d]pyrimidine analogues as antifolates.

Abstract: We report, for the first time, the biological activities of four-carbon-atom bridged classical antifolates on dihydrofolate reductase (DHFR), thymidylate synthase (TS), and folylpolyglutamate synthetase (FPGS) as well as antitumor activity. Extension of the bridge homologation studies of classical two-carbon bridged antifolates, a 5-substituted 2,4-diaminofuro[2,3-d]pyrimidine (1) and a 6-subsituted 2-amino-4-oxopyrrolo[2,3-d]pyrimidine (2), afforded two four-carbon bridged antifolates, analogues 5 and 6, with enhanced FPGS substrate activity and inhibitory activity against tumor cells in culture (EC50 ≤ 10-7 M) compared with the two-carbon bridged analogues. These results support our original hypothesis that the distance and orientation of the side chain p-aminobenzoyl-l-glutamate moiety with respect to the pyrimidine ring are a crucial determinant of biological activity. In addition, this study demonstrates that, for classical antifolates that are substrates for FPGS, poor inhibitory activity against is...

Effect of a bound non-nucleoside RT inhibitor on the dynamics of wild-type and mutant HIV-1 reverse transcriptase.

Abstract: HIV-1 reverse transcriptase (RT) is an important target for drugs used in the treatment of AIDS. Drugs known as non-nucleoside RT inhibitors (NNRTI) appear to alter the structural and dynamical properties of RT which in turn inhibit RT's ability to transcribe. Molecular dynamics (MD), principal component analysis (PCA), and binding free energy simulations are employed to explore the dynamics of RT and its interaction with the bound NNRTI nevirapine, for both wild-type and mutant (V106A, Y181C, Y188C) RT. These three mutations commonly arise in the presence of nevirapine and result in resistance to the drug. We show that a bound NNRTI hinders the motion of almost all RT amino acids. The mutations, located in the non-nucleoside RT inhibitor binding pocket, partially restore RT flexibility. The binding affinities calculated by molecular mechanics/Poisson-Boltzmann surface accessibility (MM-PBSA) show that nevirapine interacts stronger with wild-type RT than with mutant RT. The mutations cause a loss of van der Waals interactions between the drug and the binding pocket. The results from this study suggest that a good inhibitor should efficiently enter and maximally occupy the binding pocket, thereby interacting effectively with the amino acids around the binding pocket.

Highly Efficient Copper-Mediated Atom-Transfer Radical Addition (ATRA) in the Presence of Reducing Agent

Abstract: The synthesis, characterization and exceptional activity of Cu I (TPMA)Br [TPMA = tris(2-pyridylmethyl)amine] and [Cu II (TPMA)Br][Br] complexes in ATRA reactions of polybrominated compounds to alkenes in the presence of reducing agent (AIBN) was reported. [Cu II (TPMA)Br][Br], in conjunction with AIBN, effectively catalyzed ATRA reactions of CBr 4 and CHBr 3 to alkenes with concentrations between 5 and 100 ppm, which is the lowest number achieved in copper-mediated ATRA. The molecular structure of Cu I (TPMA)Br indicated that the complex was pseudo-pentacoordinate in the solid state due to the coordination of TPMA [Cu I -N: 2.1024(15), 2.0753(15), 2.0709(15) and 2.4397(14) A] and bromide anion to the copper(I) center [CU I -Br 2.5088(3) A]. Variable temperature 1 H NMR and cyclic voltammetry studies confirmed the equilibrium between Cu I (TPMA)Br and [Cu I -(TPMA)(CH 3 CN)][Br], indicating some degree of halide anion dissociation in solution. The coordination of the bromide anion to the [Cu I (TPMA)] + cation resulted in a formation of much more reducing Cu I (TPMA)Br complex (E 1/2 = -720 mV vs. Fc/Fc + ) than the corresponding ClO 4 - (E 1/2 = -422 mV vs. Fc/Fc + ) and PF 6 - (E 1/2 = -421 mV vs. Fc/Fc + ) analogues. In [Cu II (TPMA)Br][Br], the Cu II atom was coordinated by four nitrogen atoms [Cu II -N eq 2.073(2) A and Cu II -N ax 2.040(3) A] from TPMA ligand and a bromine atom [Cu II -Br 2.3836(6) A]. The overall geometry of the complex was distorted trigonal bipyramidal. Cu I (TPMA)Br and [Cu II (TPMA)-Br][Br] complexes showed similar structural features from the point of view of TPMA coordination. The only more pronounced difference in the TPMA coordination to the copper center was observed in the shortening of Cu-N ax bond length by approximately 0.400 A on going from Cu I (TPMA)Br to [Cu II (TPMA)Br][Br].

Impact of multiple cation-π interactions upon calix[4]arene substrate binding and specificity

Abstract: The cation−π interaction influence on the conformation and binding of calix[4]arenes to alkali-metal cations has been studied using a dehydroxylated model. The model allows for the separation of cooperative cation−π and electrostatic forces commonly found in the binding motifs found in calixarene complexes. Starting from the four well-known calix[4]arene conformations, six conformers for this dehydroxylated model (cone, partial cone, flattened cone, chair, 1,2-alternate, and 1,3-alternate) have been characterized by geometry optimization and frequency analysis using the Becke three-parameter exchange functional with the nonlocal correlation functional of Lee, Yang, and Parr and the 6-31G(d) basis set. Without the stabilization provided by the hydroxyl hydrogen bonds in calix[4]arene, neither the cone nor the 1,2-alternate conformation is computed to be a ground-state structure. The partial cone, flattened cone, chair, and 1,3-alternate conformers have been identified as ground-state structures in a vacuum...

The Social Dimensions of Corporate Sustainability: An Integrative Framework Including COVID-19 Insights

Abstract: Corporate sustainability is considered a fundamental paradigm and solution in creating a prosperous future for organizations. However, social sustainability issues and pandemic problems from COVID-19 have affected corporations and interrupted plans for sustainable development. To date, corporate sustainability frameworks have taken a relatively narrow view of this paradigm. This study highlights serious challenges to corporate sustainability while providing a framework in an attempt to enable more sustainable business practices. To fill the gap in the literature, we have developed a framework to organize and prioritize important sustainability indicators. The first phase of the study involves the classification of 45 sub-criteria of corporate sustainability under nine main categories by using a literature review and novel Fuzzy Delphi method. The resulting categories are Corporate Governance, Product Responsibility, Transparency and Communication, Economic, Environmental, Social, Natural Environment and Climate Vulnerability, Energy Consumption along with Energy Saving, and includes Pandemic COVID-19 as a new aspect of social sustainability. Next, we applied the Fuzzy Analytical Hierarchical Process (FAHP) to help determine the weights and prioritizing the criteria and sub-criteria. The results revealed that the Pandemic, along with the Natural Environment and Climate Vulnerability, ranked higher among the main criteria category. Whereas, emergency response planning, social distances, modification of working hours, and just-in-time delivery are the most influencing sub-attributes among the 45 sub-barriers of different categories. Contributions of this study include new insights regarding corporate sustainability criteria and subcriteria, application of novel methods, and integrated framework for dimensions of corporate sustainability. This study is among the first of its kind to consider the COVID-19 pandemic as an essential category and social sustainability attribute of corporate sustainable business practices. Outcomes of this study can help assist scholars, corporations, and decision-makers in understanding sustainable development initiatives while simultaneously improving social sustainability practices.