Interaction of the Antibiotic Rifampicin with Lipid Membranes Rui M. S. Santos, Jaime Samelo, Alexandre C. Oliveira, Margarida M. Cordeiro, Maria Julia Mora, et al. Biomolecules, 2025 Rifampicin is a broad-spectrum antibiotic, active against several bacterial infections such as tuberculosis. It is a relatively large and structurally complex molecule, including numerous polar groups. Although violating several of Lipinski’s rules for efficient intestinal absorption, rifampicin shows good oral bioavailability, permeating through cell membranes in the absorption pathway and those of the target organisms. Some hypotheses have been proposed for its efficient membrane permeation, but the details are mostly unknown. In this work, the interaction of rifampicin with POPC lipid bilayers is studied using experimental biophysics methodologies and atomistic molecular dynamics simulations considering the two most prevalent ionic species at physiological pH, the anionic and the zwitterionic forms. The results show that both ionization forms of rifampicin establish favorable interactions with the membrane lipids, in agreement with the relatively high partition coefficient obtained experimentally. The results from MD simulations and isothermal titration calorimetry using different pH buffers show that the piperazine group inserts deeply in the membrane and is accompanied by a stabilization of its neutral form. The bulky nature of rifampicin and its deep insertion in the membrane lead to a strong perturbation in the lipids local order, decreasing the membrane barrier properties as evaluated from the rate of carboxyfluorescein leaching. Altogether, the comparison between the experimental and MD simulations results provides important insight regarding the rifampicin molecular features responsible for its relatively fast membrane permeation. The lipid POPC used in this study was selected as a simple membrane with relevance for different organisms across all kingdoms. Further studies using more complex lipid compositions will provide details on eventual specificities for rifampicin interaction with the membranes of distinct organisms.
Dipole Potential of Monolayers with Biologically Relevant Lipid Compositions Renato M. S. Cardoso, Fabiana Lairion, Edgardo Anibal Disalvo, Luís M. S. Loura, Maria João Moreno Molecules, 2024 The membrane dipole potential that arises from the interfacial water and constitutive dipolar groups of lipid molecules modulates the interaction of amphiphiles and proteins with membranes. Consequently, its determination for lipid mixtures resembling the existing diversity in biological membranes is very relevant. In this work, the dipole potentials of monolayers, formed at the air–water interface, from pure or mixed lipids (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine (POPE), 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidyserine (POPS), sphingomyelin (SpM) and cholesterol) were measured and correlated with the mean area per lipid. The results showed that, as previously observed, cholesterol increases the dipole potential in correspondence with the decrease in the average area per lipid. At the small mole fractions encountered in biomembranes, the presence of the negatively charged lipid POPS increases the dipole potentials of monolayers despite inducing an increase in the average area per lipid. Additionally, the inclusion of POPE in POPC:cholesterol monolayers disrupts the area condensation induced by cholesterol while increasing the membrane dipole moment, leading to a small reduction in the dipole potential. This trend is reinforced for the quaternary POPC:cholesterol:POPE:POPS 4:3:2:1 system, which mimics the inner leaflets of eukaryotic plasma membranes. In agreement with previous works, the replacement of phosphocholine lipids with sphingomyelin leads to a decrease in the dipole potential. Together, this results in a lower dipole potential for the SpM-enriched outer leaflet, generating a non-zero transbilayer dipole potential in the asymmetric plasma membranes of eukaryotic cells.
Improving the Accuracy of Permeability Data to Gain Predictive Power: Assessing Sources of Variability in Assays Using Cell Monolayers Cristiana L. Pires, Maria João Moreno Membranes, 2024 The ability to predict the rate of permeation of new compounds across biological membranes is of high importance for their success as drugs, as it determines their efficacy, pharmacokinetics, and safety profile. In vitro permeability assays using Caco-2 monolayers are commonly employed to assess permeability across the intestinal epithelium, with an extensive number of apparent permeability coefficient (Papp) values available in the literature and a significant fraction collected in databases. The compilation of these Papp values for large datasets allows for the application of artificial intelligence tools for establishing quantitative structure–permeability relationships (QSPRs) to predict the permeability of new compounds from their structural properties. One of the main challenges that hinders the development of accurate predictions is the existence of multiple Papp values for the same compound, mostly caused by differences in the experimental protocols employed. This review addresses the magnitude of the variability within and between laboratories to interpret its impact on QSPR modelling, systematically and quantitatively assessing the most common sources of variability. This review emphasizes the importance of compiling consistent Papp data and suggests strategies that may be used to obtain such data, contributing to the establishment of robust QSPRs with enhanced predictive power.
Quantifying Small-Molecule Association with Lipid Membranes: Methods, Models, and Limitations MJ Moreno, MM Cordeiro, HAL Filipe, AC Oliveira, CL Pires, CV Ramos, ... Preprints , 2026 2026
Lysosome-targeted Ru (II)–cyclopentadienyl organometallic anticancer complexes RG Teixeira, L Stenico, X Fontrodona, I Romero, R Starosta, MJ Moreno, ... Dalton Transactions 55 (2), 594-610 , 2026 2026 Citations: 2
Electropolymerization of brilliant cresyl blue in ethaline deep eutectic solvent on graphene quantum dot modified glassy carbon electrodes: Application to dipyrone determination JMS Almeida, MJ Moreno, CMA Brett Journal of Electroanalytical Chemistry, 119691 , 2025 2025
Membrane Partition and Structural Reorganization Induced by Antipsychotics with Distinct Clinical Profiles A Gorse, V Yordanova, J Bodosa, M Mathelié-Guinlet, A Walrant, ... ACS Chemical Neuroscience 16 (19), 3728-3744 , 2025 2025 Citations: 2
Passive Transport across Cell Membranes beyond the Overton Rule: Insights from Solute Exchange in Vesicles and Molecular Dynamics of Atropisomers MM Cordeiro, AC Oliveira, PE Abreu, LG Arnaut, MJ Moreno, LMS Loura ACS Applied Materials & Interfaces 17 (16), 23575-23587 , 2025 2025 Citations: 2
Serum-PEG and BSA-PEG hydrogels as advanced platforms for evaluating plasma protein binding CDF Coelho, VS Paiva, ZL Almeida, JA Jesus, M Marteleira, CV Ramos, ... Materials Today Chemistry 45, 102565 , 2025 2025 Citations: 5
Interaction of the Antibiotic Rifampicin with Lipid Membranes RMS Santos, J Samelo, AC Oliveira, MM Cordeiro, MJ Mora, GE Granero, ... Biomolecules 15 (3), 320 , 2025 2025 Citations: 7
BPS2025-Membrane interactions and photodynamic efficacy of redaporfin atropisomers—a molecular dynamics and biophysical study MJ Moreno, MM Cordeiro, AC Oliveira, LG Arnaut, LM Loura Biophysical Journal 124 (3), 255a , 2025 2025
BPS2025-Understanding drug-membrane interactions and reconciling results from different methods: Insights from a pH variation assay MM Cordeiro, MJ Moreno, A Salvador Biophysical Journal 124 (3), 258a-259a , 2025 2025 Citations: 1
Dipole Potential of Monolayers with Biologically Relevant Lipid Compositions RMS Cardoso, F Lairion, EA Disalvo, LMS Loura, MJ Moreno Molecules 29 (24), 5843 , 2024 2024 Citations: 2
Nutrient‐efficient catfish‐based aquaponics for producing lamb's lettuce at two light intensities F Sebastião, DC Vaz, CL Pires, PF Cruz, MJ Moreno, RMM Brito, L Cotrim, ... Journal of the Science of Food and Agriculture 104 (11), 6541-6552 , 2024 2024 Citations: 9
Improving the accuracy of permeability data to gain predictive power: assessing sources of variability in assays using cell monolayers CL Pires, MJ Moreno Membranes 14 (7), 157 , 2024 2024 Citations: 13
Loss of the lysosomal protein CLN3 modifies the lipid content of the nuclear envelope leading to DNA damage and activation of YAP1 pro-apoptotic signaling N Domingues, J Pires, SR Freire, NJ Herz, T Huynh, K Wieciorek, ... bioRxiv , 2024 2024 Citations: 6
Re-use of Caco-2 monolayers for a higher throughput assessment of drug permeability–methodology and validation for passive permeation CL Pires, S Rosa, ALMB de Carvalho, L Ferreira, MPM Marques, ... Preprints , 2024 2024 Citations: 1
Interaction of MRI Contrast Agent [Gd(DOTA)] − with Lipid Membranes: A Molecular Dynamics Study AC Oliveira, HAL Filipe, CFGC Geraldes, GA Voth, MJ Moreno, ... Inorganic Chemistry 63 (24), 10897-10914 , 2024 2024 Citations: 10
Nutritive Value and Bioactivities of a Halophyte Edible Plant: Crithmum maritimum L. (Sea Fennel) I Correia, M Antunes, C Tecelão, M Neves, CL Pires, PF Cruz, ... Plants 13 (3), 427 , 2024 2024 Citations: 36
State-of-the-Art Macromolecules in Portugal AJM Valente, NC Santos, MJ Moreno International Journal of Molecular Sciences 25 (1), 620 , 2024 2024
Contribution of non-ionic interactions on bile salt sequestration by chitooligosaccharides: Potential hypocholesterolemic activity F Coreta-Gomes, IMV Silva, C Nunes, I Marin-Montesinos, D Evtuguin, ... Journal of Colloid and Interface Science 646, 775-783 , 2023 2023 Citations: 10
Interaction of Hoechst 33342 with POPC membranes at different pH values MM Cordeiro, HAL Filipe, P Santos, J Samelo, JPP Ramalho, LMS Loura, ... Molecules 28 (15), 5640 , 2023 2023 Citations: 17
Permeation of a homologous series of nbd-labeled fatty amines through lipid bilayers: A molecular dynamics study HAL Filipe, LMS Loura, MJ Moreno Membranes 13 (6), 551 , 2023 2023 Citations: 10
MOST CITED SCHOLAR PUBLICATIONS
Cholesterol and POPC segmental order parameters in lipid membranes: solid state 1 H–13 C NMR and MD simulation studies TM Ferreira, F Coreta-Gomes, OHS Ollila, MJ Moreno, WLC Vaz, ... Physical Chemistry Chemical Physics 15 (6), 1976-1989 , 2013 2013 Citations: 260
Phase coexistence and connectivity in the apical membrane of polarized epithelial cells D Meder, MJ Moreno, P Verkade, WLC Vaz, K Simons Proceedings of the National Academy of Sciences 103 (2), 329-334 , 2006 2006 Citations: 207
Exogenous loading of miRNAs into small extracellular vesicles RC de Abreu, CV Ramos, C Becher, M Lino, C Jesus, ... Journal of Extracellular Vesicles 10 (10), e12111 , 2021 2021 Citations: 131
Quaternary ammonium surfactant structure determines selective toxicity towards bacteria: mechanisms of action and clinical implications in antibacterial prophylaxis ÂS Inácio, NS Domingues, A Nunes, PT Martins, MJ Moreno, LM Estronca, ... Journal of Antimicrobial Chemotherapy 71 (3), 641-654 , 2016 2016 Citations: 116
Kinetics and thermodynamics of association of a phospholipid derivative with lipid bilayers in liquid-disordered and liquid-ordered phases MSC Abreu, MJ Moreno, WLC Vaz Biophysical journal 87 (1), 353-365 , 2004 2004 Citations: 87
How to tackle the issues in free energy simulations of long amphiphiles interacting with lipid membranes: convergence and local membrane deformations HAL Filipe, MJ Moreno, T Rog, I Vattulainen, LMS Loura The journal of physical chemistry B 118 (13), 3572-3581 , 2014 2014 Citations: 81
Production of singlet oxygen by Ru (dpp (SO3) 2) 3 incorporated in polyacrylamide PEBBLES MJ Moreno, E Monson, RG Reddy, A Rehemtulla, BD Ross, M Philbert, ... Sensors and Actuators B: Chemical 90 (1-3), 82-89 , 2003 2003 Citations: 80
Polysaccharide structures and their hypocholesterolemic potential IMV Silva, F Machado, MJ Moreno, C Nunes, MA Coimbra, ... Molecules 26 (15), 4559 , 2021 2021 Citations: 76
Translocation of phospholipids and dithionite permeability in liquid-ordered and liquid-disordered membranes MJ Moreno, LMBB Estronca, WLC Vaz Biophysical journal 91 (3), 873-881 , 2006 2006 Citations: 76
Kinetics and thermodynamics of chlorpromazine interaction with lipid bilayers: effect of charge and cholesterol PT Martins, A Velazquez-Campoy, WLC Vaz, RMS Cardoso, J Valerio, ... Journal of the American Chemical Society 134 (9), 4184-4195 , 2012 2012 Citations: 75
Kinetics and thermodynamics of association of a fluorescent lysophospholipid derivative with lipid bilayers in liquid-ordered and liquid-disordered phases JL Sampaio, MJ Moreno, WLC Vaz Biophysical journal 88 (6), 4064-4071 , 2005 2005 Citations: 65
Re-use of caco-2 monolayers in permeability assays—Validation regarding cell monolayer integrity CL Pires, C Praça, PAT Martins, ALM Batista de Carvalho, L Ferreira, ... Pharmaceutics 13 (10), 1563 , 2021 2021 Citations: 64
Binding of a fluorescent lipid amphiphile to albumin and its transfer to lipid bilayer membranes MSC Abreu, LMBB Estronca, MJ Moreno, WLC Vaz Biophysical journal 84 (1), 386-399 , 2003 2003 Citations: 59
Chain length effect on the binding of amphiphiles to serum albumin and to POPC bilayers RMS Cardoso, HAL Filipe, F Gomes, ND Moreira, WLC Vaz, MJ Moreno The Journal of Physical Chemistry B 114 (49), 16337-16346 , 2010 2010 Citations: 54
Kinetics and thermodynamics of the association of dehydroergosterol with lipid bilayer membranes LMBB Estronca, MJ Moreno, WLC Vaz Biophysical journal 93 (12), 4244-4253 , 2007 2007 Citations: 53
Uncertainty in protein–ligand binding constants: asymmetric confidence intervals versus standard errors V Paketurytė, V Petrauskas, A Zubrienė, O Abian, M Bastos, WY Chen, ... European Biophysics Journal 50 (3), 661-670 , 2021 2021 Citations: 49
Chain-length dependence of insertion, desorption, and translocation of a homologous series of 7-nitrobenz-2-oxa-1, 3-diazol-4-yl-labeled aliphatic amines in membranes RMS Cardoso, PAT Martins, F Gomes, S Doktorovova, WLC Vaz, ... The Journal of Physical Chemistry B 115 (33), 10098-10108 , 2011 2011 Citations: 47
Partition of amphiphilic molecules to lipid bilayers by isothermal titration calorimetry MJ Moreno, M Bastos, A Velazquez-Campoy Analytical biochemistry 399 (1), 44-47 , 2010 2010 Citations: 45
Interactions between rhodamine dyes and model membrane systems—insights from molecular dynamics simulations N Magalhães, GM Simões, C Ramos, J Samelo, AC Oliveira, HAL Filipe, ... Molecules 27 (4), 1420 , 2022 2022 Citations: 44
Edible flowers of Helichrysum italicum: Composition, nutritive value, and bioactivities MJ Primitivo, M Neves, CL Pires, PF Cruz, C Brito, AC Rodrigues, ... Food Research International 157, 111399 , 2022 2022 Citations: 43
