Metalloporphyrins are molecules consisting of a porphyrin ring coordinated with a metal ion, especially a transition metal. The porphyrin structure is represented by four pyrrole rings connected by methyne bridges.

Metalloporphyrins are being investigated as drug carriers, particularly in cancer treatment, due to their unique properties and their potential for targeted drug delivery [1]. They can be incorporated into various nanomaterials, like metal–organic frameworks or nanogels, or used as building blocks for drug delivery systems, leading to a controlled release and enhanced therapeutic efficacy [1]. The main advantages of this class of compounds are their biocompatibility, making them suitable for biomedical applications, and their adjustable properties. The metal ion and porphyrin structure can be modified to tailor the properties of the metalloporphyrin for specific drug delivery needs [2].

A literature survey showed various applications for various substituted metalloporphyrins. Tin-containing metalloporphyrins have been investigated as a potential treatment of neonatal hyperbilirubinemia. They act as inhibitors of the enzyme heme oxygenase, which is responsible for breaking down heme and producing bilirubin. By inhibiting this enzyme, metalloporphyrins can reduce the amount of bilirubin produced, potentially alleviating the severity of hyperbilirubinemia [3,4].

Molecular imprinting polymers with porphyrins and iron(II)porphyrins have been successfully used for the selective binding of hemoglobin [5]. The synthesized porphyrins were substituted with 4-allyloxyphenyl residues on the methine bridges.

Metalloporphyrins (metal range: Ca-Zn) were investigated as possible drug carriers for fluorouracil by computational chemistry methods. The results showed that the highest affinity was obtained for Ti-porphyrin [6]. Manganese(III) porphyrin complexes have been synthesized and characterized; their antibacterial, antifungal, and antioxidant activity has been investigated [7]. They were effective inhibitors of the Gram-positive strains S. aureus and B. cereus; also, they present an enhanced sensitivity towards C. krusei, sensitivity that increases for the metalloporphyrins compared to the free porphyrins [7].

Another series of free-base porphyrins and metalloporphyrins have been synthesized and evaluated for possible antitumor activity [8]. Good results have been obtained for the free porphyrins and Zn-porphyrins; the positive influence of the substituents has been emphasized for benzene substituted with electron-attracting groups [8].

Metalloporphyrins substituted with benzenesulfonic acid have been synthesized and characterized; metalloporphyrins of three lanthanides (Pr, Eu, and Ce) have been obtained [9]. The porosity and magnetic properties of these compounds make them suitable for gas storage, catalysis, and sensing applications.

Another study investigates the influence of the energy levels of lanthanide ions on the luminescence properties of metalloporphyrins [10]. Specifically, the presence and position of f-orbital energy levels relative to the porphyrin’s singlet (S1) and triplet (T1) excited states dictate whether energy transfer occurs, affecting the type and intensity of luminescence observed [8]. The ability to modify the luminescence properties of metalloporphyrins by selecting specific lanthanide ions with specific energy levels is valuable for developing materials with desired optical properties for various applications, including bioimaging and sensing. According to the authors, the choice of lanthanide ion energy levels is important for designing and synthesizing metalloporphyrins with specific optic characteristics.

Another study [11] presents the applications of metalloporphyrins in diagnostic imaging, including MRI (metalloporphyrins can be designed to enhance contrast in MRI scans, improving the visibility of tumors and other tissues); fluorescence imaging (porphyrins can be used as fluorescent probes for bio-imaging applications, enabling the visualization of specific cellular targets); or PET, SPECT, and CT. Porphyrin derivatives can be radiolabeled with various isotopes for use in Positron Emission Tomography (PET), Single-Photon Emission Computed Tomography (SPECT), and Computed Tomography (CT) imaging.

The use of specific nanomaterials in drug delivery systems has significantly advanced cancer therapy by improving both the efficiency and delivery of therapeutic agents. These materials, including nanoparticles, liposomes, and nanogels, have properties such as enhanced drug solubility, protection from degradation, and targeted delivery to tumoral tissues, minimizing side effects on healthy cells. Metal–organic frameworks based on porphyrin can entrap a range of therapeutic agents, resulting in the application of these materials for drug delivery in cancer therapy [12].

The present study aims to investigate the electronic, geometric, and steric properties of 10 Dy(III)-porphyrins, with the general structure depicted in Figure 1:

A previous work [13] has dealt with the evaluation of some substituted porphyrins with fluorine, hydroxyl, aminoethyl, and hydroxyethyl groups as possible photosensitizers. In this regard, the same substituents have been chosen for our study involving the characterization of dysprosium porphyrins.

The optimized geometries of the investigated series of compounds have been employed for the calculation of the energetic parameters like the total energy per atom and the HOMO–LUMO gap.

The results presented in Table 1 summarize the values of the total energy/atom calculated for the metalloporphyrins.

The analysis of the calculated energies/atom shows that the grafted methylene group on the methyne bridges (compounds 2, 4, 6, 8, and 10) leads to a decrease in the stability of the proposed metalloporphyrin structures. The aforementioned results also suggest that the presence of a halogen atom (especially chlorine) increases the stability of the compounds. The lowest values were obtained for the methyl-substituted Dy-porphyrin (2), followed by the one substituted with the aminomethyl group (8).

The influence of the substituents on the investigated metalloporphyrins has also been evaluated by means of the HOMO-LUMO gap. The energy difference between the frontier molecular orbitals is considered a good indicator of the stability/reactivity of a compound: larger HOMO-LUMO gaps suggest an increased stability, while smaller HOMO-LUMO gaps are correlated with enhanced reactivity.

The obtained values of the frontier molecular orbitals, together with the calculated HOMO-LUMO gaps, are depicted in Table 2.

According to these results, all the investigated metalloporphyrins are characterized by lower stability. The presence of the substituents strongly influences the value obtained. In general, the presence of -X group on the methyne bridges leads to the obtained of slightly higher HOMO-LUMO gaps, compared to the ones that also have a methylene group, -CH₂X. A single exception occurred, regarding the unsubstituted Dy-porphyrin 1, that is characterized by a smaller energy gap of the frontier molecular orbitals compared to the methyl-substituted structure 2.

The visualization of HOMO (Highest Occupied Molecular Orbital) and LUMO (Lowest Unoccupied Molecular Orbital) is a key parameter for organic compounds, helping to understand and predict the stability, reactivity, and electronic properties of a molecule. In the field of drug design and pharmaceutical applications, the distribution of the HOMO and LUMO orbitals offer insights regarding the potential interaction sites with biological targets, together with the evaluation of the stability and reactivity of the compounds.

Graphical representation of the frontier molecular orbitals HOMO and LUMO has been performed. The results are presented in Figure 2, Figure 3, Figure 4 and Figure 5 and outline some differences among the studied Dy-porphyrins.

According to the results illustrated in Figure 2, Figure 3, Figure 4 and Figure 5, the same pattern is encountered in the distribution of the HOMO orbitals for the compounds 1, 2, 3, 5, 7, and 9 (the unsubstituted porphyrin and the ones with CH₃, F, NH₂, and OH grafted on the methyne bridge). For these compounds, the HOMO orbitals appear localized mostly on the pyrrole rings. Instead, the porphyrins 4, 6, 8, and 10 (substituted with CH₂X groups) show that the HOMO orbitals are also localized on the methyne group and on the grafted CH₂X moiety. As exception, the porphyrins 7 and 8 (substituted with amino and methyamino groups) are characterized by a lesser delocalization of the HOMO orbitals (on two of the four substituents). This situation is correlated to the lowest values of the HOMO energy computed for compounds 7 and 8, as depicted in Table 2. Instead, the LUMO orbitals are mostly localized on the four methyne bridges and, to a small extent, on the substituents (excepting the compounds 4 and 6, substituted with CH₂F and CH₂Cl, respectively). The results of LUMO energies presented in Table 2 show the lower values calculated for compounds 7–10, the ones substituted with amino and hydroxyl groups.

The steric and geometric properties of the proposed Dy-porphyrins have also been calculated (Table 3). Steric properties like the molecular surface and volume provide a way to visualize the shape and size of molecules, aiding in understanding their overall structure. They are also used in virtual screening of potential drug candidates, assessing surface similarity and complementarity to target molecules.

The analysis of these parameters shows, as expected, larger values for the -CH₂X-substituted compounds (compared to the X-substituted ones). Larger values for these parameters have been obtained for chloromethyl- (6), aminomethyl- (8), and hydroxymethyl- (10) Dy-porphyrins. The same compounds—6, 8, and 10—are characterized by the highest ovality, a steric parameter that measures the deviation from the spherical shape of a compound.

Polar surface area (PSA) is a molecular descriptor employed in medicinal chemistry, especially for predicting how well a molecule will pass through cell membranes. It represents the combined surface area of all polar atoms (mainly oxygen and nitrogen, including their attached hydrogen atoms) within a molecule [15]. PSA is a key parameter for assessing a drug’s ability to be absorbed; molecules with a PSA above 140 Ų generally have poor membrane permeability, making them less likely to be absorbed effectively [16]. For molecules to cross the blood–brain barrier, a PSA below 60 Ų is generally preferred [16]. Polarizability represents the tendency of a molecule’s electron cloud to distort in response to an electric field. This distortion results in an induced electric dipole moment. The degree of polarizability is strongly influenced by the number of electrons and the size of the molecule. It also plays a key role in determining the strength of intermolecular interactions.

The results depicted in Table 4 show that the polar surface area of the investigated compounds is found to be within the range 17–120 Ų. A significant increase is obtained for compounds 7–10, the ones that bear hydroxyl and amino groups.

The analysis of the influence of substituents on the geometric properties of the Dy-porphyrins also dealt with the length measurements of the Dy-N bonds. The results are depicted in Table 5, while the numbering of the atoms involved is presented in Figure 6.

Also, taking into account the non-planar structure of the Dy-porphyrins (see the side-view depicted in Figure 7), the values of the angles formed by the nitrogen atoms and dysprosium have been determined.

The present study analyzed the geometric and electronic properties of some Dy-porphyrins, substituted with various groups. The results showed that, according to the computed HOMO-LUMO gap, the most stable are compounds 7 and 9, the porphyrins bearing amino and hydroxyl groups. The above-mentioned compounds are characterized by bond lengths of approximately 2.44 Å for Dy-N(sp3) and 2.42 Å for Dy-N(sp2).

Considering the calculated energy per atom of the compounds within the series, the substitution with atoms leads to an increase in this parameter, together with the increase in the atomic number of the substituting atoms. The highest values have been obtained for chlorine -Cl, followed by fluorine –F, hydroxyl –OH, and amino –NH2. The presence of the CH2 group in compounds 4, 6, 8, and 10 leads to a decrease in the total energy.

The frontier molecular orbital energies HOMO and LUMO are correlated with their symmetrical or unsymmetrical distribution (see compounds 7 and 8).

According to the general structure of the investigated Dy-porphyrins depicted in Figure 7 and to the results presented in Table 6, most of the proposed structures are characterized by the values of the angles between the sp3 nitrogen atoms and Dy of ~125°, while the values of the angles between the sp2 nitrogen atoms and Dy are close to ~131°.