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Article

Biophysical Characterization of Membrane Interactions of 3-Hydroxy-4-Pyridinone Vanadium Complexes: Insights for Antidiabetic Applications

by
Luísa M. P. F. Amaral
1,*,
Tânia Moniz
1,2 and
Maria Rangel
2
1
LAQV, REQUIMTE, Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade do Porto, Rua do Campo Alegre, s/n, 4169-007 Porto, Portugal
2
LAQV, REQUIMTE, Instituto de Ciências Biomédicas de Abel Salazar, Universidade do Porto, Rua Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal
*
Author to whom correspondence should be addressed.
Inorganics 2025, 13(10), 311; https://doi.org/10.3390/inorganics13100311
Submission received: 25 July 2025 / Revised: 9 September 2025 / Accepted: 22 September 2025 / Published: 24 September 2025
(This article belongs to the Special Issue New Trends in Vanadium Chemistry, Biochemistry, and Medicinal Chemistry, 2nd Edition)
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Abstract

The development of metallopharmaceuticals for diabetes treatment has garnered increasing attention due to its insulin-mimetic properties, particularly in vanadium complexes. In this study, we report the biophysical evaluation of a series of 3-hydroxy-4-pyridinone (3,4-HPO) vanadium complexes, designed to improve lipophilicity and biological cytocompatibility. Dynamic light scattering (DLS) was used to get insight on the size of the liposomes and Differential Scanning Calorimetry (DSC) was employed to investigate the interaction of these complexes with model biological membranes made from dimyristoylphosphatidylcholine (DMPC) unilamellar liposomes. The thermotropic phase behavior of the lipid bilayers was analyzed in the presence of vanadium complexes. The results reveal that the alkyl chain length of the 3,4-HPO ligands modulates membrane interaction of the respective vanadium compounds, with specific complexes inducing significant shifts in the lipid phase transition temperature (Tm), suggesting alterations in membrane fluidity and packing. These findings provide valuable insight into the membrane affinity of vanadium-based drug candidates and support their potential as next-generation antidiabetic agents.

Graphical Abstract

1. Introduction

Diabetes mellitus (DM) is a chronic metabolic disorder characterized by persistent hyperglycemia due to impaired insulin secretion, insulin action, or both. The global prevalence of diabetes has prompted extensive research into alternative therapeutic strategies beyond conventional insulin therapy. Among these, vanadium compounds have garnered attention for their insulin-mimetic properties, demonstrating the ability to enhance glucose uptake and modulate lipid metabolism in various biological systems [1,2,3]. Vanadium exists in multiple oxidation states, with vanadyl (IV) and vanadate (V) forms exhibiting distinct biological activities. Vanadyl compounds have been shown to facilitate glucose transport across cellular membranes, while vanadate species can influence intracellular signaling pathways involved in glucose and lipid metabolism [1].
Many studies have demonstrated that vanadium complexes with various oxidation states cause different biological effects. However, regarding the antidiabetic properties of vanadium, the most extensively studied complexes are those containing V(IV) and V(V), as documented in a review published in [1].
Concerning V(V), it should be noted that vanadium (V) complexes are often more labile and hydrolytically sensitive in aqueous medium, frequently undergoing reduction to V(IV) in the presence of biological reductants. Nonetheless, V(V) species such as peroxovanadates have been investigated for their insulin-mimetic properties, although their instability remains a challenge.
V(III) compounds are not stable under biological conditions, which limits their relevance for antidiabetic studies, as their biotransformation may significantly affect their pharmacological potential [4].
Therefore, our study focused on V(IV) complexes because they provide a compromise between synthetic accessibility, solution stability, and biological relevance. We fully recognize that both V(III) and V(V) complexes are of high interest, and future work will aim to expand the scope of this research to include these oxidation states to compare their stability, membrane interaction, and potential biological activity.
Despite promising results in preclinical studies, the clinical application of vanadium compounds has been limited by concerns over toxicity and bioavailability [5,6,7,8,9,10,11]. To address these challenges, researchers have explored the development of organo-vanadium complexes, wherein vanadium is chelated with organic ligands to enhance stability and reduce toxicity. Among these ligands, 3-hydroxy-4-pyridinone (3,4-HPO) has emerged as a promising candidate due to its strong metal-binding affinity and favorable chemical and pharmacokinetic properties [12,13,14,15,16].
In a previous study, we characterized bis(3-hydroxy-4-pyridinonato) oxidovanadium(IV) complexes in aqueous solution (pH 7.4) under aerobic conditions using EPR and 51V Nuclear Magnetic Resonance (NMR) techniques (as reviewed in [1]). Complexes with ligands of varying alkyl chain lengths displayed distinct solubility profiles, impacting their behavior in solution and within POPC liposome suspensions. Electron Paramagnetic Resonance (EPR) spectra confirmed that the predominant V(IV) species present was [VOL2], which underwent gradual oxidation in air to V(V) species such as [VO2L2]−, [VO2L], and H2VO4−, all detectable by 51V NMR. The addition of sodium ascorbate effectively reversed this oxidation. The use of dimethylsulfoxide (DMSO) slowed the oxidation and introduced distinct solvation environments around [VOL2], suggesting direct DMSO coordination. These findings underscored the critical influence of ligand lipophilicity and solvent environment on complex stability, thereby establishing a foundation for further investigation of their interactions with biomimetic membranes. Subsequently, we explored the interaction of a series of 3,4-HPO chelators with varying alkyl chain lengths with DMPC liposomes using DSC and EPR techniques, complemented by computational modeling and simulations, to provide a more comprehensive understanding of their behavior and structural impact in model biological membrane environments, as discussed in [17]. These studies highlighted that ligand lipophilicity critically influences membrane interactions, with longer alkyl chains significantly perturbing lipid phase behavior.
In the present study, we extend this work to evaluate a series of V(IV) 3,4-HPO complexes with systematically varied alkyl chain lengths to investigate their interactions with DMPC liposomes using DSC. By analyzing shifts in phase transition temperatures and changes in enthalpy, we aim to elucidate how ligand lipophilicity modulates membrane affinity of the vanadium complexes. These insights will contribute to the rational design of optimized antidiabetic agents with enhanced biological membrane interactions.
The interaction of therapeutic agents with biological membranes is a critical factor influencing their efficacy and distribution. Model membranes, such as those composed of dimyristoylphosphatidylcholine (DMPC), serve as valuable tools for investigating drug-membrane interactions. Dynamic light scattering (DLS) was used to get insight on the size of the liposomes, while differential scanning calorimetry (DSC) was employed as a sensitive technique to assess changes in membrane thermotropic behavior upon interaction with various compounds. Table 1 summarizes the chemical formulae for the series of vanadium (IV) complexes discussed in the present study.

2. Results and Discussion

2.1. Liposome Size Determination

The size distribution of the liposomes, including the mean hydrodynamic diameter and polydispersity index (PDI), was determined by DLS. To evaluate the effect of vanadium complexes on liposome size, DLS measurements were also performed on samples containing mixtures of the complexes with DMPC. The resulting particle sizes and PDI values are presented in Table 2. No significant changes (p > 0.05) in liposome size or PDI were observed upon incorporation of the vanadium complexes, indicating that none of the complexes altered the overall size distribution of the liposomes.

2.2. DSC Analysis of Vanadium Complex Effects on DMPC Liposomes

To assess the impact of the vanadium complexes on the thermotropic properties of the DMPC LUVs, we prepared stock solutions in DMSO and introduced them into the DMPC suspension at a final concentration of 2 mM. The maximum concentration of DMSO added to the DMPC did not exceed 1%. The DMPC concentration used in the DSC sample cell was 3 mM. After one hour of incubation at 37 °C to allow for equilibration, the samples were subjected to DSC analysis. DSC heating scans provided insight into shifts in Tm, changes in the enthalpy of transition (ΔH), and variations in ΔT1/2. According to literature, pure DMPC LUVs generally show a sharp main endothermic transition near 24 °C, corresponding to the gel (Lβ′) to liquid-crystalline (Lα) phase transition, commonly referred to as the melting temperature (Tm) [18,19,20]. The width of this transition at half its maximum height (ΔT1/2) serves as a measure of the cooperativity of the process. The enthalpy change associated with this transition (ΔH), which reflects the amount of energy required to disrupt the ordered gel phase into the more disordered liquid-crystalline phase, provides insight into the strength of the lipid–lipid interactions within the bilayer.
The DSC results presented in Table 3 reveal the impact of vanadium complexes on the thermotropic behavior of DMPC. Pure DMPC LUVs (no vanadium compound added) exhibit a sharp main phase transition at 24.5 °C, with a narrow transition width (ΔT1/2) of 0.8 °C and a transition enthalpy (ΔH) of 20.2 kJ·mol−1, consistent with literature values.
Upon incorporation of vanadium complexes, distinct effects on the phase transition parameters are observed, depending on the alkyl chain length and structure of the ligand. Complexes with short-chain ligands such as VO(mpp), VO(dmpp), and VO(etmpp) have negligible effects on Tm and ΔT1/2, maintaining values close to those of pure DMPC. However, longer-chain complexes, particularly VO(butmpp), VO(hexylmpp), and VO(hexyletpp), induce a clear reduction in Tm (down to 22.9 °C for VO(hexylmpp) and VO(hexyletpp), accompanied by a broadening of the transition (ΔT1/2 up to 1.3 °C) and changes in enthalpy.
These results indicate a disruption of the lipid packing and reduced cooperativity of the phase transition, suggesting that the longer alkyl chains enhance the interaction of the complex with the hydrophobic core of the lipid bilayer, altering membrane order and dynamics. Interestingly, an increase in ΔH is only observed for VO(hexylmpp) and VO(hexyletpp), which may reflect the formation of more stable or ordered domains due to specific interactions of these complexes with the membrane.
To further explore how the compounds modulate membrane behavior, we extended our analysis to include a concentration-dependent study. Complexes that mostly altered the thermotropic profile of DMPC (VO(butnmpp), VO(hexylmpp), and VO(hexyletpp)) in the initial screen were reevaluated over a broader concentration range (0.5 to 2 mM), maintaining the same concentration of DMPC. This approach aimed to elucidate the nature and strength of their interaction with the lipid bilayer.
Representative DSC thermograms for selected DMPC/complex systems are shown in Figure 1, and the corresponding thermodynamic parameters are summarized in Table 4. These results provide insight into the effects of three vanadium complexes, VO(butnmpp), VO(hexylmpp), and VO(hexyletpp), on the thermotropic behavior of DMPC. Specifically, changes in the main phase transition temperature (Tm), transition width (ΔT1/2), and transition enthalpy (ΔH) were evaluated to quantify the interaction with the lipid bilayers.
For the VO(butmpp) complex, a slight but consistent decrease in Tm was observed with increasing concentration, from 24.5 °C at 0.5 mM to 23.9 °C at 2.0 mM. The ΔT1/2 values showed an increase (from 0.8 to 1.2 °C), indicating a gradual loss of cooperativity of the main phase transition. However, the enthalpy changes remained relatively constant (~19.3–19.7 kJ·mol−1), suggesting minimal disruption to the overall lipid packing.
In contrast, the VO(hexylmpp) complex exerted a more pronounced effect on the bilayer structure. A concentration-dependent decrease in Tm was observed (24.0 °C to 22.9 °C), accompanied by an increase in both ΔT1/2 (from 0.8 to 1.3 °C) and ΔH (from 23.5 to 24.1 kJ·mol−1). These results suggest that VO(hexylmpp), likely due to its longer alkyl chain, has stronger interactions with the hydrophobic core of the membrane, leading to increased fluidization and possibly deeper insertion into the bilayer. The VO(hexyletpp) complex exhibited a similar trend. Compared to VO(butmpp), both VO(hexylmpp) and VO(hexyletpp) displayed a more significant effect on the thermotropic properties of DMPC, which can be attributed to their enhanced lipophilicity due to longer alkyl substituents.

2.3. UV-Vis Analysis of Vanadium Complex Effects

The UV-Vis absorption spectra of the vanadium complexes were recorded in DMSO, HEPES buffer, and in DMPC liposome suspensions to evaluate their solubility and potential interactions with biomimetic membranes.
In this study, the absorbance band attributed to the pyridinone ring was chosen due to the inability to detect the expected V(IV) or V(V) bands, which typically appear around 400–800 nm [21]. The non-observation of these bands is attributed to the low concentration of the complexes (a maximum of 0.5 mM) utilized in the studies, alongside the lower molar extinction coefficient of vanadium bands in comparison to that of the ligand.
Furthermore, vanadium oxidation is anticipated to occur, a phenomenon observed in similar conditions for this class of complexes [1]. Such oxidation would induce changes in the intensity and wavelength of the bands associated with vanadium transitions, thereby compromising the reliability of their analysis.
Consequently, examining the pyridinone band allows for more precise conclusions which are expected to relate predominantly to the solubility of the compounds and will be less influenced by the contribution of the oxidation process, offering clearer insights into the compounds’ behavior.
The maximum absorbance values (A) and corresponding wavelengths (λ), depicted in Table 5, varied depending both on the complex and on the solvent providing insights into solvent-dependent solubility and electronic environment.
In general, all complexes show high absorbance values in DMSO from 292 to 304 nm, consistent with the well-known ability of this solvent to efficiently dissolve coordination compounds due to its high polarity and aprotic nature.
In contrast, a noticeable decrease in absorbance is observed for several complexes in HEPES buffer, suggesting reduced solubility in aqueous media. This effect is especially pronounced for VO(hexylmpp) and VO(hexyletpp), which show significantly lower absorbance values in HEPES (A = 0.779 and 1.244, respectively), likely due to their increased hydrophobic character conferred by the longer alkyl chains. These results support the hypothesis that hydrophobic substitution can impair solubility in aqueous environments. Interestingly, the incorporation of DMPC liposomes appears to enhance the solubility of these complexes. VO(hexylmpp) and VO(hexyletpp) show marked increases in absorbance in the presence of DMPC compared to HEPES alone (A = 1.649 and 1.720 vs. 0.779 and 1.244, respectively). This observation suggests that the lipid bilayer can provide a suitable microenvironment for incorporating hydrophobic complexes, likely through partitioning into the membrane phase.
This trend is consistent with previously reported DSC data (Table 3 and Table 4), which demonstrated enhanced interaction and membrane affinity of these hexyl-substituted complexes with DMPC bilayers.
VO(detpp) displays distinct UV-Vis features depending on the solvent environment. In DMSO, the complex shows high solubility, reflected by a strong absorbance (A = 2.557) while in HEPES buffer the absorbance decreases significantly (A = 1.573), indicating lower solubility. The absorbance remains similarly low in the presence of DMPC liposomes, implying that incorporation into the lipid bilayer does not significantly enhance the apparent solubility or dispersion of this complex in a membrane-mimetic environment. Structurally, the Hdetpp ligand features an ethyl substituent on the nitrogen atom as well as in the R2 position, placing it in an intermediate position on the hydrophobicity scale. This moderate lipophilicity may not be sufficient to promote effective partitioning into the hydrophobic core of the lipid bilayer, while still limiting aqueous solubility due to decreased polarity. On the other hand, the remaining complexes exhibit comparable absorbance values in HEPES and DMPC, suggesting a weaker interaction with the lipid bilayer.

3. Materials and Methods

3.1. Chemicals

Reagents and solvents were purchased from Merck (Darmstadt, Germany), and used as received, 1,2-ditetradecanoyl-sn-glycero-3-phosphocholine (DMPC, PC, 14:0 PC), was acquired from Avanti Polar Lipids (Alabama, AL, USA), stored at −18 °C, and used without additional purification. The buffer solution (HEPES buffer) was prepared by accurately weighing 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid to a final concentration of 10 mM, with 150 mM NaCl, and adjusted to pH 7.4.
The oxidovanadium(IV) complexes used in this study were synthesized by us as previously described [21,22,23]. A brief description of the synthesis of the ligands and complexes is provided in the Supporting Information. Stock solutions of the vanadium complexes were prepared in DMSO.

3.2. Preparation of Liposomes

Unilamellar liposomes (LUVs) composed of DMPC were prepared using the film hydration method followed by freeze–thaw cycles and extrusion. Briefly, DMPC was dissolved in a mixture of chloroform/methanol (87.4:12.6% (v/v)) and the solvent was evaporated under a gentle stream of nitrogen to form a thin lipid film on the walls of a round-bottom flask. The lipid film was further dried under vacuum for at least 4 h to ensure complete removal of residual solvent.
The dry lipid film was then hydrated with HEPES buffer (10 mM HEPES, 150 mM NaCl, pH 7.4) preheated to 37 °C, to achieve a final lipid concentration of 6 mM. The suspension was vortexed vigorously to form multilamellar vesicles (MLVs). To promote unilamellarity, the MLVs were subjected to five freeze–thaw cycles by alternating immersion in liquid nitrogen and a 37 °C water bath. The resulting lipid suspension was extruded 20 times through a polycarbonate membrane with 100 nm pore size (Whatman, Nuclepore, Nova Jersey, NJ, USA) using a 10 mL stainless steel extruder (Lipex Biomembranes Inc., Vancouver, BC, Canada) maintained at 37 °C. This procedure yielded large unilamellar vesicles (LUVs) with a uniform size distribution. The lipid content in the liposomal suspension was determined by a spectrophotometric method as previously described [24].

3.3. Vesicle Size Distribution

The average size of the extruded liposomes was measured by dynamic light scattering (DLS) using a Nano Zetasizer (Malvern Panalytical Ltd., Malvern, Worcestershire, UK). The measurements were conducted at a total lipid concentration of 0.1 mM and a temperature of 37 °C, employing a He-Ne laser (633 nm wavelength) as the light source and a backscattering angle of 173°. In addition to measuring the size of the liposomes used in the DSC experiments, we also performed DLS analyses on the liposome–complex mixtures used in the experiments.

3.4. Differential Scanning Calorimetry (DSC)

Thermotropic phase transition studies of DMPC were performed using a MicroCal VP-DSC microcalorimeter (Malvern Panalytical Ltd., Malvern, Worcestershire, UK). Prior to sample analysis, baseline scans were recorded with HEPES buffer (10 mM, 150 mM NaCl, pH 7.4) in both the reference and sample cells, to ensure thermal equilibration and accurate blank subtraction.
Each sample was subjected to three consecutive heating and cooling scans over the temperature range of 15–35 °C, at a constant scan rate of 60 °C/h. The reference cell remained filled with HEPES buffer during all measurements. To assess reproducibility and sample preparation consistency, the experiments were repeated using three independently prepared DMPC dispersions and freshly prepared compounds solutions.
Calorimetric data were analyzed using MicroCal Origin™ software version 7.0. Phase transition temperatures (Tm), enthalpy changes (ΔH), and the half-width at half-maximum (ΔT1/2) were determined by integration of the heat capacity (Cp) versus temperature (T) curves. A linear baseline was applied, and blank correction was performed by subtracting the buffer–buffer baseline scan from each thermogram.

3.5. Ultraviolet-Visible Absorption Studies

Ultraviolet-Visible (UV-Vis) absorption spectra were recorded in a 96-well microplate format, using a Thermo Scientific Multiskan GO Microplate Spectrophotometer (Thermo Fisher Scientific Corporation, Waltham, MA, USA). The absorption spectra were acquired in the 200–800 nm range at a temperature of 37 °C.
In each well, a total volume of 200 µL was used, to obtain 0.5 mM of the vanadium complex and 3 mM of DMPC liposomes. For comparison, control samples were prepared in DMSO and HEPES buffer without lipids, maintaining the same complex concentration. In mixed solvent system DMPC/DMSO, the DMSO content did not exceed 1% v/v to ensure liposome integrity. Preliminary tests showed that undiluted samples saturated the UV-Vis signal; therefore, all samples were diluted (50% v/v) with the corresponding solvent prior to measurement, resulting in final concentrations of 0.25 mM for the vanadium complexes and 1.5 mM for DMPC in the liposome-containing samples.
All measurements were performed in triplicate, and the data were corrected for background absorbance using appropriate solvent blanks.

4. Conclusions

Our findings collectively suggest that certain vanadium complexes, especially those with longer hydrophobic chains, exhibit limited solubility in water but demonstrate enhanced compatibility with lipid environments. This improved solubility and/or partitioning into DMPC bilayers is crucial, as it has significant implications for their bioavailability and ability to target membranes within biological systems.
Previous studies explored a series of 3-hydroxy-4-pyridinonato oxidovanadium(IV) complexes for their potential insulin-like activity, specifically their ability to inhibit free fatty acid (FFA) release in isolated rat adipocytes. Among these, VO(mpp)2 stood out as a promising complex, showing the most significant inhibitory effect on FFA release [22]. However, those studies did not investigate the effect of vanadium complexes with longer alkyl substituents on the aromatic pyridinone ring, such as VO(hexylmpp) and VO(hexyletpp).
The antidiabetic mechanism of these compounds likely involves enzyme (de)activation, redox reactions, and membrane alterations. The most widely accepted hypothesis points to the inhibition of tyrosine kinases and phosphatases, particularly protein tyrosine phosphatase 1B (PTP-1B), within the insulin signaling cascade [1,25,26]. Since these enzymes are located in the cell’s cytosol, the interaction of these compounds with cell membranes is critical for them to enter the cell and reach their intended targets.
Increased lipophilicity alone does not guarantee enhanced antidiabetic activity, as demonstrated by VO(mpp)2, which contains the shortest alkyl substituent yet exhibits significant biological activity. Nevertheless, the literature reports suggest that within certain series of vanadium complexes, higher lipophilicity can promote membrane penetration and bioavailability, thereby facilitating access to intracellular targets and contributing to insulin-mimetic effects [27,28,29]. At present, no studies have been conducted on VO(hexylmpp) and VO(hexyletpp), preventing any definitive correlation between lipophilicity, membrane interaction, and biological activity.
Given these findings, we hypothesize that VO(hexylmpp) and VO(hexyletpp), due to their superior ability to interact with membrane models compared to VO(mpp)2, may exhibit an increased antidiabetic effect. This makes them highly promising candidates for novel drug development. Furthermore, their strong affinity for liposomes suggests they could be valuable for liposome-based drug delivery strategies.
Overall, these results underscore the delicate balance between hydrophilicity and lipophilicity in influencing the solubility and membrane interaction potential of vanadium complexes. The goal of our study was to assess how structural modifications of 3,4-HPO ligands influence their interaction with lipid membranes, thus shedding light on their physicochemical behavior. Our findings provide an essential foundation for future in vitro and in vivo studies aimed at clarifying the relationship between membrane affinity and antidiabetic efficacy.

Supplementary Materials

The following supporting information can be downloaded at: https://www.mdpi.com/article/10.3390/inorganics13100311/s1.

Author Contributions

Conceptualization, L.M.P.F.A. and T.M.; Data curation, L.M.P.F.A. and T.M.; Formal analysis, L.M.P.F.A.; Investigation, L.M.P.F.A.; Resources, M.R.; Writing—original draft, L.M.P.F.A.; Writing—review and editing, L.M.P.F.A., T.M. and M.R. All authors have read and agreed to the published version of the manuscript.

Funding

This research received funding from PT national funds (FCT/MCTES, Fundação para a Ciência e Tecnologia and Ministério da Ciência, Tecnologia e Ensino Superior) projects UIDP/50006/2020 (DOI: 10.54499/UIDP/50006/2020) and UIDB/50006/2020 (DOI: 10.54499/UIDB/50006/2020).

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

Not applicable.

Data Availability Statement

The original contributions presented in this study are included in the article/Supplementary Material. Further inquiries can be directed to the corresponding author.

Acknowledgments

This work received support from PT national funds (FCT/MCTES, Fundação para a Ciência e Tecnologia and Ministério da Ciência, Tecnologia e Ensino Superior) through projects: (LA/P/0008/2020 DOI 10.54499/LA/P/0008/2020, UIDP/50006/2020 DOI 10.54499/UIDP/50006/2020 and UIDB/50006/2020 DOI 10.54499/UIDB/50006/2020). L. Amaral also thanks FCT/MCTES funding through the Individual Call to Scientific Employment Stimulus 2018 (CEECIND/03202/2018) DOI 10.54499/CEECIND/03202/2018/CP1545/CT0001.

Conflicts of Interest

The authors declare no conflicts of interest.

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Inorganics 13 00311 g001
Figure 1. The DSC heating thermograms for the main phase transition of DMPC unilamellar vesicles (LUVs), in the presence and absence of different concentrations of: (a) VO(butmpp); (b) VO(hexylmpp); (c) VO(hexyletpp).
Figure 1. The DSC heating thermograms for the main phase transition of DMPC unilamellar vesicles (LUVs), in the presence and absence of different concentrations of: (a) VO(butmpp); (b) VO(hexylmpp); (c) VO(hexyletpp).
Inorganics 13 00311 g001
Table 1. Formulae and numbering of vanadium (IV) complexes.
Table 1. Formulae and numbering of vanadium (IV) complexes.
Vanadium Complex Formulae SubstituentsLigand AbbreviationComplex Abbreviation
R1R2
Inorganics 13 00311 i0011HCH3HmppVO(mpp)
2CH3CH3HdmppVO(dmpp)
3CH3-CH2CH3HetmppVO(etmpp)
4CH3-(CH2)3CH3HbutmppVO(butmpp)
5CH3-(CH2)5CH3HhexylmppVO(hexylmpp)
6HCH3-CH2HetppVO(etpp)
7CH3-CH2CH3-CH2HdetppVO(detpp)
8CH3-(CH2)3CH3-CH2HbutetppVO(butetpp)
9CH3-(CH2)5CH3-CH2HhexyletppVO(hexyletpp)
Table 2. Diameter (d) and polydispersity index (PDI) of the liposomes.
Table 2. Diameter (d) and polydispersity index (PDI) of the liposomes.
Complexd (nm) aPDI a
DMPC112.4 ± 0.80.063 ± 0.018
VO(mpp)112.3 ± 0.80.040 ± 0.005
VO(dmpp)114.2 ± 1.10.035 ± 0.009
VO(etmpp)111.1 ± 1.00.043 ± 0.008
VO(butmpp)112.8 ± 1.90.034 ± 0.010
VO(hexylmpp)115.1 ± 1.00.070 ± 0.002
VO(etpp)111.6 ± 0.90.053 ± 0.007
VO(detpp)113.5 ± 1.20.056 ± 0.008
VO(butetpp)108.7 ± 0.80.044 ± 0.006
VO(hexyletpp)108.6 ± 0.70.049 ± 0.009
a Mean and standard deviation of three independent experiments.
Table 3. Main phase transition thermodynamic parameters (Tm, ΔT1/2 and ΔH) of DMPC LUVs with 2 mM of complex added a.
Table 3. Main phase transition thermodynamic parameters (Tm, ΔT1/2 and ΔH) of DMPC LUVs with 2 mM of complex added a.
Tm/°CΔT1/2/°CΔH/kJ·mol−1
DMPC24.50.820.2
VO(mpp)24.50.821.0
VO(dmpp)24.40.820.2
VO(etmpp)24.40.820.9
VO(butmpp)23.91.219.5
VO(hexylmpp)22.91.324.1
VO(etpp)24.40.820.2
VO(detpp)224.40.819.7
VO(butetpp)224.50.821.1
VO(hexyletpp)222.91.123.5
a The estimated uncertainty is ±0.2 °C for the transition temperature, ±0.2 °C for the half width at half height, and ±1.5 kJ·mol−1 for the enthalpy.
Table 4. Main phase transition thermodynamic parameters (Tm, ΔT1/2 and ΔH) for increased complex concentrations in DMPC LUV’s a.
Table 4. Main phase transition thermodynamic parameters (Tm, ΔT1/2 and ΔH) for increased complex concentrations in DMPC LUV’s a.
Tm/°CΔT1/2/°CΔH/kJ·mol−1
DMPC (no complex added)24.50.819.6
DMPC + VO(butmpp) 0.5 mM24.50.819.3
DMPC + VO(butmpp) 1.0 mM24.21.019.7
DMPC + VO(butmpp) 2.0 mM23.91.219.5
DMPC + VO(hexylmpp) 0.5 mM24.00.823.5
DMPC + VO(hexylmpp) 1.0 mM23.61.024.5
DMPC + VO(hexylmpp) 2.0 mM22.91.324.1
DMPC + VO(hexyletpp) 0.5 mM24.01.022.7
DMPC + VO(hexyletpp) 1.0 mM23.71.022.0
DMPC + VO(hexyletpp) 2.0 mM22.91.123.5
a The estimated uncertainty is ±0.2 °C for the transition temperature, ±0.2 °C for the half width at half height, and ±1.5 kJ·mol−1 for ΔH.
Table 5. UV-Vis spectral parameters of vanadium complexes in different solvent environments (DMSO, HEPES buffer, and DMPC liposomes).
Table 5. UV-Vis spectral parameters of vanadium complexes in different solvent environments (DMSO, HEPES buffer, and DMPC liposomes).
ComplexA (DMSO)λ (DMSO) (nm)A (HEPES)λ (HEPES) (nm)A (DMPC)λ (DMPC) (nm)
VO(mpp)2.1272942.4962742.310274
VO(dmpp)2.2533022.5922862.507286
VO(etmpp)2.6403022.5002862.634286
VO(butmpp)2.3323022.6992842.762284
VO(hexylmpp)1.9913020.7792821.649286
VO(etpp)2.3232962.8232762.800276
VO(detpp)2.5573041.5732841.571284
VO(butetpp)2.7963042.3852842.368286
VO(hexyletpp)1.2812921.2442801.720282
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Amaral, L.M.P.F.; Moniz, T.; Rangel, M. Biophysical Characterization of Membrane Interactions of 3-Hydroxy-4-Pyridinone Vanadium Complexes: Insights for Antidiabetic Applications. Inorganics 2025, 13, 311. https://doi.org/10.3390/inorganics13100311

AMA Style

Amaral LMPF, Moniz T, Rangel M. Biophysical Characterization of Membrane Interactions of 3-Hydroxy-4-Pyridinone Vanadium Complexes: Insights for Antidiabetic Applications. Inorganics. 2025; 13(10):311. https://doi.org/10.3390/inorganics13100311

Chicago/Turabian Style

Amaral, Luísa M. P. F., Tânia Moniz, and Maria Rangel. 2025. "Biophysical Characterization of Membrane Interactions of 3-Hydroxy-4-Pyridinone Vanadium Complexes: Insights for Antidiabetic Applications" Inorganics 13, no. 10: 311. https://doi.org/10.3390/inorganics13100311

APA Style

Amaral, L. M. P. F., Moniz, T., & Rangel, M. (2025). Biophysical Characterization of Membrane Interactions of 3-Hydroxy-4-Pyridinone Vanadium Complexes: Insights for Antidiabetic Applications. Inorganics, 13(10), 311. https://doi.org/10.3390/inorganics13100311

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