Solvent dependent structural, electronic, and optical properties of ureidopeptidomimetics: a DFT and TD-DFT study on the effects of donor and acceptor functional groups

Abstract

This study provides a comprehensive examination of the structural, electronic, optical, and reactivity properties of ureidopeptidomimetics (UPMs) featuring various donor and acceptor functional groups using density functional theory (DFT) and time-dependent DFT (TD-DFT). To systematically explore their effects on charge transfer, HOMO-LUMO energy gaps, and molecular stability, the molecular models were intentionally designed with both electron-donating groups (–CH₃, –OCH₃, –OH, –NH₂) and electron-accepting groups (–SH, –COCl, –CF₃). A detailed analysis of the bond lengths confirmed the electron-rich nature of the substituents, revealing that the introduction of electron-donating groups at the ureido and carboxylate terminals of the UPMs decreased the C–O and C–N bond lengths by 0.005 Å and 0.0003 Å, respectively, compared to the unsubstituted UPM. Polar solvents, notably water and DMSO, enhance the stabilization of HOMO and LUMO energy levels, thus improving the electronic stability and reactivity of UPM molecules, as demonstrated by DFT and TD-DFT calculations. In the case of UPM, the molecular orbitals (HOMO: −6.8646 eV to −6.9027 eV, LUMO: −0.3957 eV to −0.4248 eV) experienced slight stabilization as it transitioned from the gas phase to the aqueous phase. This transition increased the chemical potential (χ) and global hardness (η), signifying enhanced electronic stability. UV-Vis experiments revealed that UPM's λ_max values remained around 218.6 nm across various solvents, with polar solvents, particularly water, exhibiting more robust oscillators. In water, λ_max decreased to 207.58 nm for D2-UPM-A2 and shifted to 227.86 nm for D1-UPM-A1. For D3-UPM-A3, λ_max in water exhibited a redshift to 249.28 nm along with reduced absorption. Specifically, for A1-UPM-D1 and A2-UPM-D2, the polarity of the solvent influenced transitions and increased transition probabilities, indicating their potential in optoelectronic applications.

Introduction

The first successful clinical application of bioactive peptides dates back to 1922 when insulin was administered to treat a patient with type I diabetes [1]. This breakthrough marked the beginning of significant interest in bioactive peptides as a foundation for therapeutic drug development. In the 1950s, Sanger’s determination of insulin’s amino acid sequence paved the way for chemists to explore peptides as a novel class of pharmaceutical agents [2]. Several naturally occurring bioactive peptides, particularly hormones such as insulin and vasopressin, are utilized clinically in their unmodified forms, while others, such as calcitonin and glucagon-like peptide 1 analogues, are chemically modified to enhance their properties [3]. However, most bioactive peptides face challenges for therapeutic use due to poor pharmacokinetic profiles, including low metabolic stability, rapid clearance, poor oral bioavailability, and low membrane permeability [4].

Peptidomimetics are synthetic compounds designed to mimic the structure and function of natural peptides, but with modifications that provide enhanced stability, bioavailability, and other desirable properties. These compounds are invaluable in various fields, including drug discovery, biotechnology, and material science, due to their ability to interact with biological targets in a highly specific manner. Peptidomimetics are particularly useful in overcoming some of the limitations associated with natural peptides, such as their susceptibility to enzymatic degradation and poor membrane permeability [5]. Peptidomimetics can be designed to mimic specific sequences or structural motifs found in bioactive peptides, such as hormones, enzymes, or neurotransmitters. These synthetic analogues are often created by modifying peptide bonds, replacing amino acid residues with non-natural analogues, or introducing cyclic structures to improve stability and function. The goal is to preserve the biological activity of the parent peptide while overcoming its limitations [6].

One important class of peptidomimetics is ureidopeptidomimetics, which incorporates ureido groups (–NH–C(O)–NH–) into the peptide backbone. These groups offer enhanced stability and provide additional sites for molecular recognition, making them promising candidates for therapeutic and diagnostic applications. Ureidopeptidomimetics have been explored for their potential in drug delivery, enzyme inhibition, and molecular recognition, and their structural flexibility makes them adaptable for various applications [7]. The use of peptidomimetics has been particularly effective in designing molecules that can mimic the structure and function of bioactive peptides such as insulin, glucagon, and peptide hormones like vasopressin. For example, modifications in the peptide structure can improve half-life, enhance receptor affinity, and prevent proteolytic cleavage, making them more effective as therapeutic agents [8].

To overcome these limitations, researchers have developed peptidomimetics, which involves designing structural analogues using non-canonical amino acids or non-peptidic frameworks. Non-canonical amino acids and non-peptidic frameworks are integral to the design of peptidomimetics, offering significant advantages over natural peptides. These modifications enhance the stability, bioactivity, and selectivity of peptidomimetics, and they have broad applications in drug discovery, chemical biology, and biotechnology [9, 10]. Non-peptidic frameworks refer to structural elements in peptidomimetics that are not derived from amino acids but are designed to mimic the peptide backbone or other essential features of the peptide structure [11]. The use of non-canonical amino acids and non-peptidic frameworks in peptidomimetics has expanded the potential for drug discovery by offering more options for chemical modification, leading to molecules with enhanced bioactivity, stability, and specificity. These modifications allow for better optimization of lead compounds, overcoming the limitations of natural peptides, and facilitating the development of novel therapeutics that can target previously inaccessible biomolecules or signalling pathways [12].

This approach improves the pharmacokinetic properties of peptides [13]. Additionally, peptidomimetics provides advantages in terms of binding potency and target specificity by incorporating conformational constraints. Molecules can adopt multiple conformations due to the free rotation around single bonds, but only one bioactive conformation interacts with the target biomolecule. Restricting the flexibility of a biologically active compound often enhances its specific binding affinity by stabilizing its active conformation [14, 15]. This concept is also valuable for identifying the bioactive conformation of a molecule and has been widely applied in the design of peptidomimetics [16]. A key aspect of peptidomimetic design is replicating the secondary structures, such as β-turns, γ-turns, α-helices, or β-strands, which are critical for interactions with target biomolecules [17]. These structural motifs often mediate peptide–protein or peptide–receptor interactions. For instance, G-protein coupled receptors (GPCRs) typically recognize the turn conformations of their endogenous ligands [18], while proteolytic enzymes are more likely to recognize extended β-strand conformations of their substrates[19]. Consequently, numerous conformationally constrained scaffolds have been developed to mimic these structural features and optimize target binding.

Recent innovations have also focused on modifying ureidopeptide (UP) bonds by replacing the oxygen atom in the urea carbonyl group with less electronegative elements, such as sulphur or selenium [20]. Sulphur-containing peptides exhibit distinct chemical, physical, and biological properties due to their lower electronegativity, making them highly intriguing for further exploration [21, 22]. It is anticipated that UP derivatives will display similar properties [23–25]. Studies on their electronic, absorption, and charge transfer characteristics suggest potential applications in areas such as photosensors and photoswitches. For this purpose, investigations into the electronic structures, absorption spectra, and charge transduction processes of these molecules were performed using density functional theory (DFT).

Over the past decade, computational methods have gained widespread acceptance for peptide and protein design, with new advancements appearing regularly. This surge in computational approaches is fuelled by improvements in computing power, user-friendly molecular modelling software, and access to comprehensive databases like the Cambridge Structural Database (CSD), the Protein Data Bank (PDB), and Swiss-Prot/TrEMBL [26].

In recent years, research has demonstrated the potential of ureido-functionalized compounds for use in photonic and optoelectronic applications. For instance, studies on fluorescein-based derivatives have shown solute-solvent interactions leading to bathochromic shifts and emission in the visible range, making them suitable for photonic devices [27]. Similarly, the field of photoactivated peptides, which employs light-sensitive groups for precise spatiotemporal control of biological activity, highlights the potential for designing light-responsive ureidopeptidomimetics [28].

Computational approaches now play a pivotal role in the drug design process, complementing experimental methodologies. In particular, computational chemistry has been instrumental in the rational design of ureidopeptidomimetics, providing insights into their conformational behaviour and interactions with biological targets [29]. DFT, initially developed to address problems in solid-state physics [30, 31], has become a reliable method for molecular structure analysis [32, 33]. It accounts for electron correlation effects, which are crucial for understanding conformational energetics. While early applications of DFT relied on local density functionals (LDF), modern practices increasingly favour gradient-corrected nonlocal functionals (NLF), which offer greater accuracy in predicting geometries and conformational energetics [34–36]. NLF-DFT has been shown to rival, and sometimes surpass, traditional post-Hartree–Fock methods in terms of computational efficiency and precision, making it a valuable tool in the study of complex molecular systems.

Computational methods

Design of molecules

In the present work, a series of new molecules was strategically designed, focusing on variations in functional group placement and composition. These variations were selected to tailor the molecular properties for specific applications. The design framework emphasized a systematic approach to modifying molecular structures, ensuring the desired properties and performance metrics were achieved.

Figure 1 illustrates the molecular representations, which were central to the design and computational studies. These representations served as the basis for theoretical analyses and property optimizations. The results from this design approach contribute to the development of advanced molecular systems with enhanced functionality, addressing challenges in energy-related applications. The design involved the development of D-UPM-A molecular models, where: D represents electron-donating groups (–CH₃, –OCH₃, –OH, –NH₂). A represents electron-accepting groups (–SH, –COCl, –CF₃). This structure was chosen to systematically study the effect of donor-acceptor interactions on the electronic properties of the molecules. Strategic variation in functional groups was aimed at tuning properties such as charge transfer, HOMO-LUMO energy levels, and molecular stability.

Computational methods

All calculations were performed using the Gaussian 09 software package [37]. Ground-state electronic structures of ADP molecules were optimized using Density Functional Theory (DFT), while Time-Dependent Density Functional Theory (TD-DFT) was employed for optimizing the excited state structures. TD-DFT is recognized as an effective method for describing excited states. For all calculations, Becke’s three-parameter hybrid exchange functional combined with the Lee-Yang-Parr correlation (B3LYP functional) and the B3LYP/6–311++G(d, p) basis set were utilized [38, 39]. The Polarizable Continuum Model (PCM) was used to study the solvent effects on the molecules, as PCM is known to provide a reliable treatment for biological molecules [40, 41]. The solvents used in this study included methanol (ε  =  32.6), acetonitrile (ε  =  37.5), DMSO (ε  =  47), and water (ε  =  78.5). The solvents selected (ε  =  32.6 to 78.5) represent a range of polarities suitable for understanding the solute-solvent interactions in systems where polar interactions are predominant. Since the focus of our study was to evaluate the photophysical behaviour of the compounds in polar environments, nonpolar or low-polarity solvents like cyclohexane (ε  =  2.0) and chloroform (ε  =  4.7) were not prioritized. Excited-state calculations were carried out using TDDFT, and geometry optimization at the first excited state was performed to understand the geometrical changes occurring in this state.

Results and discussions

The UPM models utilized for the computations were generated by substituting electron donors and acceptors in both the ureido group side and the carboxylic side. These models are designated as D1-UPM-A1, D2-UPM-A2, D3-UPM-A3, D4-UPM-A4 and A1-UPM-D1, A2-UPM-D2, A3-UPM-D3 with D = –CH₃, –OCH₃, –OH, –NH₂: A = –SH, –COCl, –CF₃. Each model comprises D-UPM-A and A-UPM-D structures, as illustrated in Figs 2 and 3. The distinguishing factor among them is the donor and acceptor groups between the ureido and carboxylate ends, thereby extending the peptide chain length. This setup enables the comparison of results regarding the influence and reproducibility of the distance between the donor and acceptor.

Structural and electronic properties

In this study, the optimized structures of all D-UPM-A and A-UDM-D molecular models were obtained using the DFT/B3LYP method for the ground state and the TD-DFT/B3LYP method for the excited state. The optimized geometrical structures are shown in Figs 2 and 3, while Tables 1 and 2 provide detailed structural parameters. All models were analysed and optimized as part of this work, with their energetics thoroughly evaluated.

The relaxation process reveals that similar to natural peptides and unsubstituted UPMs, the conformers with all bonds oriented in a trans configuration possess the lowest energy. Structural parameter analysis indicates that the substitution of electron-donor groups at the ureido and carboxylate ends of UPM results in a reduction of the C–O and C–N bond lengths by 0.005 Å and 0.0003 Å, respectively, compared to unsubstituted UPM (as shown in Tables 1 and 2). This reduction in bond length can be attributed to the electron-donating nature of the substituents. Regardless of the model employed, the groups substituted at the ureido end demonstrate their ability to donate electrons, confirming their role as electron-rich groups.

The geometrical parameters of Ureidopeptidomimetics (D-UPM-A and A-UPM-D) were analysed in different solvents using Density Functional Theory (DFT). The parameters include bond lengths (rC–A, rC–N, rC = O, RO–C, RC = O) and bond angles (N–C–A). These parameters were evaluated to understand the influence of solvent environments on the molecular geometry and stability of various UPM derivatives. The study shows that the geometric parameters of ALL models are generally sensitive to the solvent environment, with polar solvents like water and DMSO inducing notable changes in bond lengths and angles compared to gas. The ureido and carboxylate ends of the molecules respond differently to salvation, with the carbonyl bonds showing the most significant changes. This is likely due to the polar nature of these bonds, which interact more strongly with polar solvents through dipole interactions and hydrogen bonding.

Implications for molecular stability and reactivity

The observed changes in bond lengths and angles due to solvent effects imply that the stability and reactivity of all UPM models can be significantly influenced by the solvent environment. Longer bond lengths in polar solvents suggest increased flexibility and potential for interaction with other molecules or ions in solution. This information is crucial for designing UPMs for specific applications, such as drug delivery or as catalysts in chemical reactions, where the solvent environment can be optimized to enhance desired properties.

Frontier molecular orbital (FMOs)

The Frontier Molecular Orbitals (FMOs) of the studied molecules were computed using the DFT method with the B3LYP functional and the 6–311++G(d, p) basis set. Figures 4 and 5 illustrate the molecular orbital structures of the D-UPM-A and A-UPM-D models in the gas phase. The HOMO and LUMO energy levels, as well as the energy gap (ΔE) between them, were calculated for both the gas phase and various solvents. The results are presented in Tables 3 and 4 and visualized in Figs 4 and 5. These findings provide a comprehensive understanding of the electronic properties and reactivity of the molecules in different environments, highlighting the effect of solvation on orbital energy levels and the corresponding energy gap.

The results section presents the findings from Tables 3 and 4 and Figs 6 and 7, illustrating the energy gap (ΔE) variations for different Ureidopeptidomimetics (UPM) across diverse solvents: Gas, Methanol, Acetonitrile, DMSO, and Water. The HOMO-LUMO energy gap (ΔE) is a vital parameter in assessing the electronic and optical properties of the studied UPM derivatives. The analysis includes models D-UPM-A and A-UPM-D, each with distinct substituents, evaluated in the gas phase and various solvents. The findings reveal significant trends and insights: The D-UPM-A model was studied with substituents D1 (–CH₃), D2 (–OCH₃), D3 (–OH), and D4 (–NH₂). These substituents display varying electronic effects: Gas Phase: D3 (–OH) and D4 (–NH₂), with strong electron-donating effects, exhibit the smallest ΔE values. This reduction in ΔE is due to a stabilization of the HOMO level and a relative destabilization of the LUMO. D1 (–CH₃) and D2 (–OCH₃), being weaker donors, show larger ΔE values, indicating reduced HOMO destabilization. Solvent Effects: The energy gap consistently decreases in polar solvents for all substituents. Stronger effects are observed for D3 (–OH) and D4 (–NH₂) in highly polar solvents like DMSO and water. This behaviour reflects enhanced stabilization of the molecular orbitals by salvation.

The A-UPM-D model was analysed with substituent’s A1 (–SH), A2 (–COCl), and A3 (–CF₃), each introducing distinct electronic characteristics: Gas Phase: A3 (–CF₃), a strong electron-withdrawing group, has the smallest ΔE. This arises from a significant lowering of the HOMO energy and an increase in LUMO energy. A1 (–SH) shows the largest ΔE due to its weak electron-donating nature, resulting in minimal orbital perturbation. A2 (–COCl), with intermediate electron-withdrawing strength, displays ΔE values between those of A1 and A3. Solvent Effects: ΔE values decrease with increasing solvent polarity across all substituents. A3 (–CF₃) exhibits the most pronounced reduction in ΔE in polar solvents due to its strong interaction with solvent molecules. Solvent-dependent stabilization effects are moderate for A2 (–COCl) and minimal for A1 (–SH).

The D-UPM-A model shows generally lower ΔE values compared to the A-UPM-D model, reflecting the stronger electronic impact of D1–D4 substituents. In polar solvents, D3 (–OH) and D4 (–NH₂) exhibit the most significant reductions ΔE among all studied substituents. Both models demonstrate that ΔE decreases as solvent polarity increases, but the extent depends on the substituents' electronic nature. Electron-donating groups in D-UPM-A and electron-withdrawing groups in A-UPM-D are most sensitive to solvation effects. The reduction in ΔE, particularly in polar solvents, suggests red-shifted absorption spectra and enhanced charge transfer properties. These trends make the studied models attractive candidates for optoelectronic applications such as organic photovoltaics and LEDs. Substituents like D4 (–NH₂) and A3 (–CF₃), with the lowest ΔE in their respective models, are especially promising for these applications due to their strong electronic modulation capabilities.

Global chemical reactivity descriptors

The global chemical reactivity descriptors of the molecules, including ionization potential (IP), electron affinity (EA), electronegativity (χ), global softness (S), global hardness (η), chemical potential (μ), and electrophilicity index (ω), were determined using the Frontier Molecular Orbital (FMO) energies (E_HOMO and E_LUMO) [42, 43]. Among these, electronegativity and hardness are particularly important molecular properties for interpreting and understanding the stability and reactivity of molecular systems [44].

Quantum mechanical techniques have been widely employed to calculate molecular descriptors for QSAR (Quantitative Structure-Activity Relationship) studies [45]. These descriptors, including molecular volumes, describe molecular shape, binding interactions, and reactivity. The HOMO and LUMO energies are among the most widely recognized quantum chemical descriptors because they represent the reactive species that drive various chemical reactions [46]. The HOMO energy reflects a molecule’s sensitivity to electrophilic attack and is directly associated with the ionization potential (IP). Conversely, the LUMO energy indicates a molecule’s susceptibility to nucleophilic attack and correlates with the electron affinity (EA). Together, the HOMO and LUMO energies govern radical reactions and provide insights into the molecular stability, reactivity, and ability to interact with soft or hard nucleophiles and electrophiles.

Tables 3 and 4 present the calculated chemical and global reactivity descriptors for the studied molecules, including ionization potential (IP), electron affinity (EA), electronegativity (χ), global hardness (η), softness (S), chemical potential (μ), electrophilicity index (ω), charge transfer (ΔN_max), nucleofugality (ΔE_n), and electrofugality (ΔE_e). These descriptors provide insights into the molecules’ electronic properties, stability, and reactivity in various environments. The descriptors are critical for understanding the interaction of the molecules with electrophiles and nucleophiles, as well as their overall chemical behaviour, aiding in the prediction of reaction mechanisms and molecular stability.

The global reactivity descriptors for the studied molecules were computed in the gas phase and various solvents, as reported in Tables 3 and 4. For molecule UPM, the gas phase and solvent environments influence the electronic properties significantly. In the gas phase, the HOMO energy level was calculated as −6.8646 eV, and the LUMO was −0.3957 eV, yielding an ionization potential (IP) of 6.8646 eV and electron affinity (A) of 0.3957 eV. In solvents, there is a slight stabilization of both HOMO and LUMO levels, with values such as −6.9027 eV (HOMO) and −0.4248 eV (LUMO) in water. This stabilization increases the chemical potential (χ) and global hardness (η), indicating enhanced electronic stability in polar solvents like DMSO and water compared to the gas phase.

The D1-UPM-A1 molecule exhibits moderate shifts in the HOMO and LUMO energy levels in different media. For instance, in the gas phase, the HOMO and LUMO were calculated as −6.6279 eV and −0.5565 eV, respectively, while in water, these levels shifted to −6.8320 eV and −0.5404 eV. These shifts result in minor variations in the chemical hardness and electrophilicity index, suggesting that this molecule maintains consistent reactivity across different polar and nonpolar environments. D2-UPM-A2 demonstrates significant variations in reactivity descriptors when transitioning between phases. In the gas phase, the molecule showed the highest global hardness and electrophilicity values, indicative of lower chemical softness. The presence of solvents, particularly methanol and water, reduces the global hardness, enhancing the molecule's ability to participate in charge transfer processes. For D3-UPM-A3, the gas phase calculations reveal a HOMO of −7.3884 eV and a LUMO of −0.5859 eV. Solvents stabilize the molecular orbitals, as evidenced by the HOMO/LUMO energies in DMSO (−7.2682 eV and −0.4593 eV). The chemical potential and global softness are less sensitive to the choice of solvent, suggesting the molecule retains its reactivity characteristics in various environments.

The global chemical reactivity descriptors for D4-UPM-A4 were analyzed in the gas phase and various solvent environments, including methanol, acetonitrile, DMSO, and water. In the gas phase, the ionization potential (IP) and electron affinity (EA) were calculated as 6.7781 eV and 0.9562 eV, respectively, yielding a chemical potential (μ) of −3.8671 eV and a global hardness (η) of 2.9109 eV. The electrophilicity index (ω) was 2.5687 eV, indicating moderate reactivity. Solvent effects resulted in slight stabilization of HOMO and LUMO energies, with water showing the most significant reduction in the HOMO-LUMO gap (6.0711 eV). This stabilization enhanced the chemical potential and global softness (S), reflecting improved electronic stability in polar solvents. Across all solvents, the electrophilicity index remained consistent, indicating that solvation had a minimal impact on the molecule’s reactivity.

The solvent effect on all studied molecules is apparent, with polar solvents such as water and methanol inducing greater stabilization of the frontier molecular orbitals (HOMO and LUMO). This leads to enhanced chemical stability and lower reactivity. Additionally, the differences in reactivity descriptors (ΔE and ΔN) across solvents highlight the role of the dielectric constant and solvent polarity in modulating molecular reactivity. A comparative analysis across molecules reveals that D2-UPM-A2 has the highest global electrophilicity index in all phases, making it the most electrophilic molecule in the series. Conversely, D3-UPM-A3 exhibits greater chemical potential, indicative of its stronger nucleophilic tendencies. These findings align with the electronic structures of the molecules, as inferred from the HOMO-LUMO gaps. The results underscore the significant impact of solvents on the global reactivity descriptors of the studied molecules. Polar solvents stabilize the electronic structures, enhancing chemical hardness and reducing reactivity. The results highlight the sensitivity of D4-UPM-A4 to the surrounding environment, with solvation effects primarily influencing orbital energies and hardness. These insights are crucial for tailoring molecular properties for applications in energy conversion and storage systems.

The A1-UPM-D1 molecule demonstrates minimal solvent-induced variations in the frontier molecular orbitals. In the gas phase, the HOMO and LUMO energies were −6.9678 eV and −0.7690 eV, respectively, leading to a HOMO-LUMO gap of 6.1988 eV. Solvents stabilize the molecular orbitals, as observed in water, where the HOMO and LUMO energies shift to −6.9267 eV and −0.7140 eV, respectively. This stabilization is accompanied by slight reductions in the global hardness (η) and increases in electrophilicity (ω). The relatively high ω in polar solvents suggests that A1-UPM-D1 is more reactive in such environments, enhancing its electrophilic nature.

A2-UPM-D2 exhibits the largest variations in reactivity descriptors across different phases. In the gas phase, the HOMO and LUMO were calculated as −7.2056 eV and −1.7891 eV, yielding the highest global hardness (η = 4.4974 eV) among all molecules. This indicates significant stability and low softness. Polar solvents such as DMSO and water reduce the global hardness, with η values of 2.6254 eV and 2.6275 eV, respectively. This suggests that A2UPM-D2 becomes chemically softer in polar environments, enhancing its ability to engage in charge transfer reactions. The molecule’s electrophilicity index (ω) remains high across all solvents, with a maximum of 10.9398 eV in the gas phase, indicating strong electrophilic behaviour.

For A3-UPM-D3, the gas phase HOMO-LUMO gap was calculated as 6.4265 eV, reflecting moderate chemical stability. In solvents, the HOMO and LUMO energies are slightly stabilized, as seen in methanol (−7.0635 eV and −0.5938 eV, respectively). The chemical potential (χ) and global softness (s) exhibit minor variations, with the softness slightly increasing in polar solvents. Interestingly, the electrophilicity index (ω) for A3-UPM-D3 is consistently lower than A2-UPM-D2 but higher than A1-UPM-D1, suggesting moderate reactivity and a balanced ability to act as both a nucleophile and an electrophile in different environments.

The impact of solvents on the global reactivity descriptors is significant across all molecules. Polar solvents such as water and DMSO enhance the stabilization of molecular orbitals, reducing the HOMO-LUMO gap. This effect is more pronounced for highly electrophilic molecules like A2-UPM-D2, where the reduced global hardness and increased softness highlight improved reactivity in polar environments. The electrophilicity index (ω) generally increases with solvent polarity, reinforcing the molecules’ potential as electron acceptors in chemical interactions. This trend aligns with the solvation effect, where polar solvents stabilize charges on the molecule, promoting reactivity. Among the studied molecules, A2-UPM-D2 consistently exhibits the highest global hardness and electrophilicity index, making it the most stable and reactive molecule in the series. A1-UPM-D1 and A3-UPM-D3 display intermediate reactivity characteristics, with A3-UPM-D3 showing slightly enhanced nucleophilic tendencies due to its higher chemical potential. The results demonstrate the crucial role of solvents in modulating the electronic properties and reactivity of the studied molecules. Polar solvents enhance stability and reactivity by reducing the HOMO-LUMO gap and increasing the electrophilicity index. These insights provide a foundation for tailoring molecular properties for specific applications in areas such as energy conversion and catalysis.

Excited states and absorption spectra

The excited states of the studied molecules were calculated using the TD/DFT method for the gas phase and the PCM-TD/DFT method for the solvent phase. Tables 5 and 6 present the computed values for oscillator strength (f), excitation energy (Ex), maximum absorption wavelength (λ_max), and the major molecular orbital (MO) transitions for both gas and solvent phases. Figures 8 and 9 provide a visual comparison of the absorption spectra of the molecules, showcasing the differences in spectral patterns and regions between the gas phase and solvent environments. These results highlight the influence of solvation on the electronic transitions and absorption behaviour of the studied systems.

The UV-Vis spectral properties of the studied molecules were analysed using the TD-DFT method in the gas phase and different solvents. The computed maximum excitation wavelength (λ_max), oscillator strength (f), and molecular orbital contributions highlight the role of substitution and solvent effects on the electronic transitions. The UPM molecule exhibits a consistent λ_max of approximately 218.6 nm across all solvents. The oscillator strength (f) increases slightly in polar solvents, such as water (f = 0.0102), indicating enhanced transition probabilities. The dominant transition is from HOMO to LUMO, with contributions exceeding 81% in the gas phase and up to 93% in water. This indicates the minimal influence of solvent polarity on the electronic structure of UPM.

For D1-UPM-A1, λ_max shifts to longer wavelengths compared to UPM, with values ranging from 227.86 nm (water) to 228.88 nm (gas). The oscillator strength remains relatively stable across all solvents, with a maximum of 0.0185 in the gas phase. The transitions primarily involve HOMO to LUMO, contributing over 90% in polar solvents, demonstrating that solvent polarity stabilizes the electronic transitions. D2-UPM-A2 displays notable solvent-dependent variations in λ_max, with the longest wavelength (220.16 nm) in the gas phase and the shortest (207.58 nm) in water. In water, a complex set of transitions is observed, including contributions from HOMO-4, HOMO-3, and HOMO-2, indicating increased electronic delocalization. The oscillator strength is highest in polar solvents such as acetonitrile (f = 0.0168), suggesting that polar environments enhance transition probabilities. The D3-UPM-A3 molecule shows a pronounced redshift in λ_max compared to other derivatives, with the longest wavelength of 249.28 nm in water. This redshift indicates a lower energy gap between HOMO and LUMO. The transitions are dominated by HOMO-4 to LUMO in the gas phase (64.35%) and HOMO to LUMO in water (81.39%). The low oscillator strength (f = 0.0004–0.0005) suggests weaker absorption intensity compared to other molecules. For D4-UPM-A4, λ_max values range from 229.49 nm (water) to 236.32 nm (gas). The transitions are primarily HOMO to LUMO, with contributions exceeding 88% across all solvents. The oscillator strength increases slightly in polar solvents, such as DMSO (f = 0.0080), indicating enhanced absorption intensity in these environments.

The results show that solvent polarity significantly influences the UV-Vis absorption properties of the studied molecules. Polar solvents generally lead to slight blue or redshifts in λ_max, depending on the molecule, and enhance the oscillator strength. These shifts arise from the stabilization of the ground and excited states due to solvation effects. Molecules with higher polarity, such as D2-UPM-A2 and D3-UPM-A3, exhibit more pronounced solvent-dependent variations, highlighting their sensitivity to the surrounding environment. Among the molecules, D3-UPM-A3 exhibits the longest λ_max, indicative of the lowest HOMO-LUMO gap. This aligns with its redshifted absorption spectrum and weaker oscillator strength. Conversely, D1-UPM-A1 and D4-UPM-A4 show relatively high oscillator strengths and stable λ_max values across solvents, suggesting strong absorption properties and minimal solvent sensitivity.

The λ_max values for A1-UPM-D1 in the gas phase and solvents (acetonitrile, DMSO, methanol, and water) are consistently around 231.43 nm. The slight variations in the oscillator strength (f) and solvent polarity indicate limited solvent influence on electronic transitions for this configured ratio. Excitation Wavelength (λ_max): The λ_max values are red-shifted compared to A2-UPM-D2, ranging from 248.64 nm in the gas phase to 256.35 nm in water. This redshift indicates a stronger stabilization of the excited state in polar solvents. Excitation Wavelength (λ_max): The λ_max for A3-UPM-D3 is the shortest among the three configurations, ranging from 215.14 nm in the gas phase to 214.05 nm in water. The minimal variation indicates that solvent polarity has a negligible effect on the excitation wavelength for these configurations.

The oscillator strength increases slightly in polar solvents (e.g. DMSO and water), reaching 0.0106 in the gas phase and 0.0063–0.0066 in solvents. This suggests a minor solvent-dependent increase in transition probability. The oscillator strengths are notably weaker for A2-UPM-D2, ranging between 0.0001 and 0.0004, suggesting lower transition probabilities compared to A1-UPM-D1. This may be attributed to the unique orbital transitions associated with these configurations. The oscillator strengths for A3-UPM-D3 are moderate, ranging between 0.0036 and 0.0098, with the highest value observed in the gas phase. This indicates moderate transition probabilities regardless of the solvent environment.

Orbital Contributions for A1-UPM-D1 in the gas phase, the dominant transition involves HOMO → LUMO + 1 (68.45%) with additional minor contributions from HOMO → LUMO + 2 (18.05%) and other transitions. In polar solvents, transitions involving HOMO → LUMO + 1 dominate (76–77%), with small contributions from higher energy transitions like HOMO → LUMO + 2 and HOMO → LUMO + 3. The increased solvent polarity enhances orbital stability and transition probabilities. Orbital Contributions for A2-UPM-D2 in the gas phase, the dominant transition involves HOMO → LUMO (59.18%), with smaller contributions from other orbitals such as HOMO-1 → LUMO (15.19%) and HOMO-3 → LUMO (16.74%). In polar solvents, the HOMO → LUMO transition becomes even more dominant (∼76–77%), while contributions from higher-energy orbitals diminish. This trend reflects the stabilizing effect of solvent polarity on the HOMO-LUMO gap.

For A3-UPM-D3 in the gas phase, the dominant orbital transition is HOMO-1 → LUMO (61.19%), with smaller contributions from HOMO → LUMO (10.38%) and HOMO-4 → LUMO (15.41%). In polar solvents, the HOMO-1 → LUMO transition remains dominant (∼71–72%), while contributions from other transitions, such as HOMO-3 → LUMO, are slightly enhanced. This suggests that the solvent stabilizes specific transitions, particularly those involving the HOMO-1 orbital. The HOMO-LUMO gap’s declining trend may be interpreted as a sign of growing electron delocalization, which could improve the peptidomimetic photo physical qualities, including fluorescence and UV-Vis absorption. This is especially important when considering their application in optoelectronic devices, where materials with smaller gaps are often preferred for electronic conduction or light harvesting.

Solvent Effects on Excitations: The λ_max values generally increase (redshift) with the polarity of the solvent, with the largest shifts observed for A2-UPM-D2. This indicates a greater stabilization of the excited state in polar solvents. Oscillator Strength Variations: The oscillator strength (f) shows solvent-dependent variations, with higher values observed in polar solvents for A1-UPM-D1 and A2-UPM-D2, while A3-UPM-D3 displays minimal changes. This suggests that solvent polarity enhances the probability of electronic transitions for specific configurations. Dominance of HOMO → LUMO Transitions: For all configurations, the primary transitions involve the HOMO and LUMO orbitals. Solvent polarity tends to stabilize these orbitals, particularly for A1-UPM-D1 and A2-UPM-D2, resulting in enhanced transition probabilities and redshifted λ_max values.

The UV-Vis absorption analysis underscores the critical role of molecular structure and solvent effects on the electronic transitions of the studied molecules. The findings provide valuable insights into the design of molecules with tailored optical properties for applications in photonics and optoelectronic devices. The TD-DFT analysis revealed significant solvent effects on the excitation properties of the UPM-A model. While A1-UPM-D1 and A2-UPM-D2 configurations exhibit notable solvent-dependent redshifts and enhanced oscillator strengths, the A3-UPM-D4 configurations remain relatively unaffected by solvent polarity. These findings provide valuable insights into the electronic transitions of UPM-A derivatives and their interaction with different solvent environments, which could guide the design of materials with tailored optical properties.

Conclusions

The systematic substitution of electron-donating and electron-accepting groups in UPM derivatives significantly influences their geometric and electronic properties. Electron-donating groups (–CH₃, –OCH₃, –OH, –NH₂) reduce the HOMO-LUMO gap (ΔE) by stabilizing the HOMO, while electron-withdrawing groups (–SH, –COCl, –CF₃) induce ΔE reductions by destabilizing the LUMO. Polar solvents such as water and DMSO enhance the stabilization of frontier molecular orbitals, leading to reduced HOMO-LUMO gaps and improved charge transfer properties. This solvent-dependent modulation is most pronounced for highly polarizable substituents like –OH, –NH₂, and –CF₃, resulting in redshifted absorption spectra and increased oscillator strengths. The global reactivity descriptors, including chemical hardness, electrophilicity, and softness, highlight the solvent-induced stabilization of molecular orbitals. Polar solvents increase stability and reduce reactivity, making the molecules more suitable for energy conversion and storage applications. The UV-Vis absorption analysis reveals significant solvent effects on excitation wavelengths (λ_max) and oscillator strengths. Polar solvents enhance the probability of electronic transitions, particularly for configurations with strong electron-donating or withdrawing groups. The A2-UPM-D2 model (–COCl) and D4-UPM-A4 model (–OH) exhibit the most significant solvent-dependent changes, making them ideal candidates for optoelectronic applications.

Author contributions

Y. Pavani (Conceptualization [lead], Data curation [lead], Formal analysis [lead], Investigation [lead], Methodology [lead]), S. Aravind (Formal analysis [equal], Visualization [equal]), K. V. Padmavathi (Formal analysis [equal]), and M. Subba Rao (Conceptualization [equal], Investigation [equal], Methodology [equal]), Nambury S. Babu (Methodology [equal], Software [equal])

Conflicts of interest

The authors declare that they have no conflicts of interest related to this work.

Funding

The authors declare that no funds, grants, or other financial support were received for conducting this study.

Data availability

The data underlying this article will be shared on reasonable request to the corresponding authorand co-authors.

References