Skip to Content

Molecules

Molecules is a leading international, peer-reviewed, open access journal of chemistry published semimonthly online by MDPI. The International Society of Nucleosides, Nucleotides & Nucleic Acids (IS3NA), Spanish Society of Medicinal Chemistry (SEQT) and International Society of Heterocyclic Chemistry (ISHC) are affiliated with Molecules and their members receive discounts on the article processing charges.

Get Alerted

Add your email address to receive forthcoming issues of this journal.

All Articles (65,809)

  • Article
  • Open Access

The widespread emergence of ultra-potent synthetic opioids in illicit drug supplies and the limited effectiveness of naloxone in reversing certain synthetic opioid overdoses highlight the urgent need for potent high-affinity opioid antagonists. This study describes an improved synthetic approach and structure-activity relationship (SAR) study of N-substituted analogs of a potent and active MOR antagonist, 3-((1S,5R,9R)-9-methyl-2-phenethyl-2-azabicyclo[3.3.1]nonan-5-yl)phenol ((1S,5R,9R)-1). Pharmacological activity of the synthesized compounds at mu (MOR), delta (DOR), and kappa (KOR) receptors was assessed via a cAMP accumulation assay, and metabolic stability was determined in a microsomal stability assay. Selected compounds underwent additional evaluation in a competition binding assay at the opioid receptors. We identified a 3,5-dichloro analog, 9w, that demonstrated superior MOR potency relative to naloxone in the cAMP assay and increased metabolic stability by 3-fold in comparison to (1S,5R,9R)-1, warranting further evaluation. Notably, no measurable MOR activity was detected for an N-cyclopropylmethyl analog, 9d. Docking and binding free energy analyses identified key differences in receptor engagement that may underlie its inactivity relative to the potent antagonist (1S,5R,9R)-1. This study describes key structural features governing opioid receptor activity and metabolic stability in N-substituted C9-methyl 5-phenylmorphans and informs our future design of MOR antagonists with improved pharmacological profiles.

Molecules

1 October 2026

Structures of morphine and 5-(3-hydroxy)phenylmorphans.
  • Review
  • Open Access

Olive oil flavoring is gaining attention as a means of improving sensory characteristics, nutritional quality, and oxidative stability. However, current evidence remains fragmented across botanical ingredients, operating conditions, and production methods. This review critically compares conventional approaches, including maceration, infusion, co-processing, and direct addition, with emerging processing strategies. Particular attention is given to the transfer of phenolic and volatile compounds, extraction performance, oil quality, energy demand, scalability, economic viability, and regulatory considerations. Conventional methods are generally accessible and cost-effective, but extended contact times and the use of fresh plant materials may increase acidity and peroxide value. Emerging technologies can accelerate and improve the control of mass transfer while promoting the recovery or retention of bioactive and aroma compounds. Nevertheless, their performance varies with the plant matrix, olive cultivar, operational parameters, and production scale. Wider commercial application is also constrained by limited standardization, substantial equipment costs, insufficient long-term evidence, and uncertain regulatory frameworks. Future studies should develop comparable protocols, explore combined processing strategies, evaluate product quality and safety during storage, and conduct robust techno-economic assessments. Validation under pilot- and full-scale conditions in diverse geographical and regulatory settings will be essential to support the safe, consistent, and economically viable production of flavored olive oils.

Molecules

1 October 2026

Flavored Vegetable Oil Processing Methods [52].
  • Article
  • Open Access

The general objective of this study was to evaluate Eucalyptus globulus bark extract as a candidate component of wood preservatives with a reduced load of synthetic biocides. Extraction conditions were screened using a 23 full factorial design with a center point, identifying 75 °C, 60% ethanol and 1 h as the highest-yielding conditions (5.94%) within the tested ranges. In four-week laboratory wood-block assays, the extract alone did not exceed 40% inhibition of wood-staining fungi, whereas hinokitiol reached complete inhibition at 0.4%. Combining the extract (5%) with hinokitiol (0.4%) achieved 95–100% inhibition, similar to the synthetic reference; because hinokitiol alone reached complete inhibition at this concentration, the extract’s contribution could not be isolated, and formulations in which the extract or hinokitiol was used instead of chlorothalonil and carbendazim alongside a copper-8-quinolinolate product retained 97–100% inhibition at half, and 90–93% at a quarter, of the copper-product dose (87% and 93% reductions in synthetic active ingredients), although the copper product alone was also fully effective at 2% and the contribution of the natural components could not be isolated at that dose. On a per-mass basis, the extract (48 h LC50 27,500 ppm) was approximately 710-fold less acutely toxic than the copper-8-quinolinolate product used as synthetic reference (38.71 ppm) in Daphnia magna bioassays. On the basis of its composition and the literature, the extract may contribute multi-target antifungal mechanisms, including metal chelation, enzyme inhibition and membrane disruption, that could complement the more stable action of hinokitiol; these mechanisms were not measured here. This work supports eucalyptus bark extract, a residue that is abundant in Chile and in other eucalypt-pulp-producing countries, as a candidate component of reduced-synthetic (hybrid) wood-protection formulations; the aquatic toxicity of the final formulations was not tested, and leaching, penetration and field-durability testing are required before practical or environmental benefits can be claimed.

Molecules

1 October 2026

Response surface plots illustrate the effects of temperature, ethanol concentration, and time on (A) crude yield and antioxidant activities: (B) DPPH, (C) ABTS, and (D) FRAP of E. globulus bark extracts. The surfaces were generated from the first-order factorial models with interaction terms fitted to the experimental data (23 design with center point). For each response, the three surfaces show the fitted model over each factor pair, holding the third factor at its center level (85 °C, 50% v/v ethanol or 2 h); symbols are observed run means averaged over the held factor, and the center run (STD5) is shown at its observed value. Surface shading maps the fitted response value (darker to lighter, lower to higher) and carries no additional information.
  • Article
  • Open Access

Antibiotic resistance limits infected-wound treatment and motivates the search for antibiotic-independent antibacterial materials. Here we report monodisperse PtPdCuFe high-entropy alloy (HEA) nanozymes with multi-enzyme activities, 2.14 ± 0.18 nm in diameter, prepared by oleylamine-assisted pyrolysis. We propose that synergistic metal interactions and abundant defects may endow the nanozymes with pH-gated peroxidase-like (POD-like), catalase-like (CAT-like), and superoxide dismutase-like (SOD-like) activities. At pH 5.5, the nanozymes exert POD-like activity to decompose H2O2 into hydroxyl radicals (•OH), triggering an ROS burst that destroys the bacterial wall, causes intracellular content leakage, and ultimately kills bacteria. At pH 7.4, they exert SOD- and CAT-like activities: ~84% of H2O2 was removed within 25 min and O2 rose to ~50% within 60 s, indicating potential to alleviate wound hypoxia, yet to be validated in future animal experiments. At the lowest effective concentration tested (16 µg·mL−1), bactericidal efficiencies against Escherichia coli and Staphylococcus aureus were ~56% and ~57%, respectively. At 64 µg·mL−1, killing reached ~90%, with >90% of bacteria showing severe membrane disruption and protein leakage. At this concentration, ~90% of mammalian cells remained viable and the hemolysis rate stayed below 5%.

Molecules

1 October 2026

Structural characterization of PtPdCuFe high-entropy alloy nanozymes. (A) TEM image of PtPdCuFe nanozymes. (B) Aberration-corrected HAADF-STEM image of PtPdCuFe nanozymes. (C) Particle-size distribution of PtPdCuFe nanozymes. (D) SAED pattern of PtPdCuFe nanozymes. (E) Single-particle GPA analysis of PtPdCuFe nanozymes. (F) EDS elemental mapping of PtPdCuFe nanozymes. (G) ICP-MS quantitative analysis of the elemental composition of PtPdCuFe nanozymes. (H) XRD pattern of PtPdCuFe nanozymes. Experiments were repeated independently (A,B,F) three times with similar results.

Highly Accessed Articles

News & Conferences

Latest Issues

Open for Submission

Journal Sections

Advances in Natural Products and Their Biological Activities
Reprint

Advances in Natural Products and Their Biological Activities

Volume III
Editors: Irwin Rose Alencar Menezes, Henrique Douglas Melo Coutinho, Almir Gonçalves Wanderley, Jaime Ribeiro-Filho
Advances in Natural Products and Their Biological Activities
Reprint

Advances in Natural Products and Their Biological Activities

Volume II
Editors: Irwin Rose Alencar Menezes, Henrique Douglas Melo Coutinho, Almir Gonçalves Wanderley, Jaime Ribeiro-Filho
XFacebookLinkedIn
Molecules - ISSN 1420-3049