Luminescent Imidazo[1,5-a]pyridine Cores and Corresponding Zn(II) Complexes: Structural and Optical Tunability

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

The manuscript presents a systematic study on the synthesis and characterization of luminescent Zn(II) complexes based on imidazo[1,5-a]pyridine ligands. The authors explore the correlation between structural modifications and photophysical properties, demonstrating the tunability of absorption and emission characteristics. Overall, the manuscript presents valuable contributions to the field of luminescent materials. Addressing the following questions and expanding the discussion could significantly enhance the clarity and impact of the findings:

 

1. Synthesis and Characterization: The authors outline the synthetic pathways and characterization techniques employed. However, the rationale behind choosing specific substituents (e.g., phenyl vs. pyridine) could be elaborated. What led to the selection of these substituents? How do they compare in terms of electronic effects on the emission properties?
2. Optical Properties: The findings on quantum yields (up to 37%) and blue shifts in emission are significant. However, the mechanism behind the observed increase in quantum yield upon Zn(II) coordination is not thoroughly discussed. Could the authors explain why coordination enhances molecular rigidity? What specific structural features contribute to this enhancement?
3. Structural Analysis: How do the structural characteristics of the complexes correlate with their luminescent behavior? Are there any observable trends in the crystal packing that might affect photophysical properties?
4. Applicability in Optoelectronics: The authors mention potential applications in OLEDs and biosensing but do not provide a detailed discussion on how their findings might translate to practical applications. What specific properties make these complexes suitable for optoelectronic applications?

Author Response

Reviewer 1

 

Comments and Suggestions for Authors

The manuscript presents a systematic study on the synthesis and characterization of luminescent Zn(II) complexes based on imidazo[1,5-a]pyridine ligands. The authors explore the correlation between structural modifications and photophysical properties, demonstrating the tunability of absorption and emission characteristics. Overall, the manuscript presents valuable contributions to the field of luminescent materials. Addressing the following questions and expanding the discussion could significantly enhance the clarity and impact of the findings:

 

1. Synthesis and Characterization: The authors outline the synthetic pathways and characterization techniques employed. However, the rationale behind choosing specific substituents (e.g., phenyl vs. pyridine) could be elaborated. What led to the selection of these substituents? How do they compare in terms of electronic effects on the emission properties?

 

We are grateful to the referee for the observation. In the present work, the ligands were selected based on their binding ability and the symmetry of the imidazopyridine core. In this context, functional groups (capable of modulating molecular orbitals) were neither varied nor investigated; instead, the variation of phenyl and pyridine substituents is solely related to the coordination ability attributed specifically to the pyridine moiety. The authors have previously examined the role of various functional groups on imidazopyridine-based ligands and their influence on optical properties. In this study, the authors aim to correlate the complexation ability, symmetry, and optical properties of closely related ligands and their corresponding Zn(II) complexes, as illustrated in Figure 1.

To clarify this aspect, the following sentence has been added in Section 2.1: The significant substitution of the pendant pyridine (at position 1 on the imidazopyridine core) ensures the typical N–N bidentate coordination motif, which is well known for enabling effective complexation reactions with various metals."

 

 

1. Optical Properties: The findings on quantum yields (up to 37%) and blue shifts in emission are significant. However, the mechanism behind the observed increase in quantum yield upon Zn(II) coordination is not thoroughly discussed. Could the authors explain why coordination enhances molecular rigidity? What specific structural features contribute to this enhancement?

 

We thank the referee for the comment. The increase in quantum yield and, more generally, the enhancement of the optical properties of the studied imidazopyridine ligands upon complexation has already been reported in detail in previous works (e.g., Cerrato, V.; Volpi, G.; Priola, E.; Giordana, A.; Garino, C.; Rabezzana, R.; Diana, E. Mono-, Bis-, and Tris-Chelate Zn(II) Complexes with Imidazo[1,5-a]Pyridine: Luminescence and Structural Dependence. Molecules 2023, 28, 3703, doi:10.3390/molecules28093703), and for this reason, they have not been discussed in the present study. To clarify this point, the following sentence has been added in Section 2.2. : “As previously reported, an intense increase in the quantum yield is appreciable after the complexation reaction of an imidazo[1,5-a]pyridine-based ligand with Zn(II), due to an important modification of the ligand conformation.” In general, for imidazopyridine systems, coordination involves the restriction of the rotation of the pendant pyridine at position 1, which participates in the coordination bond, and a modification of its angle relative to the imidazopyridine core. These aspects have been analyzed and highlighted in the articles cited in the manuscript. Ultimately, this increase in rigidity and structural strain leads to the enhanced quantum yield observed in the various cases.

 

 

1. Structural Analysis: How do the structural characteristics of the complexes correlate with their luminescent behavior? Are there any observable trends in the crystal packing that might affect photophysical properties?

We thank the referee for the suggestion. Unfortunately, it was not possible to obtain crystals of sufficient quality to determine the X-ray structures of all the synthesized complexes. For this reason, the comparison suggested cannot be carried out in the present manuscript. The work focuses primarily on the optical properties in solution, highlighting the relationship between structure and binding ability of the selected imidazopyridine ligands and their corresponding complexes.

 

1. Applicability in Optoelectronics: The authors mention potential applications in OLEDs and biosensing but do not provide a detailed discussion on how their findings might translate to practical applications. What specific properties make these complexes suitable for optoelectronic applications?

 

In general, luminescent Zn(II) complexes are gaining increasing attention for optoelectronic applications such as OLEDs and LECs due to their high chemical stability, low toxicity, and tunable photophysical properties. The studied complexes exhibit efficient fluorescence in solution and contain structurally modifiable ligands, making them suitable candidates for light-emitting materials. Unlike precious metal-based systems (such as Ir, Pd, PT), Zn(II) complexes offer a cost-effective and environmentally friendly alternative. The correlation between ligand structure and emission efficiency shown in this work provides a foundation for future optimization of zinc-based emitters for use in solid-state lighting and energy-conversion technologies. However, this work presents a study focused on the synthesis and characterization of new complexes with heterocyclic ligands. The potential application in optoelectronic devices may be the subject of future publications or patents, which would focus on well-known and fully characterized complexes, both in the solid state and in solution. The main features of luminescent zinc complexes required for potential applications in this type of technology have been outlined in the introduction and in the conclusions of the manuscript.

Author Response File: Author Response.docx

Reviewer 2 Report

Comments and Suggestions for Authors

The presented work describes the synthesis of nitrogen-containing heterocyclic ligands and zinc complexes based on them. The obtained compounds demonstrate luminescent properties. The authors tried to understand the possibilities of adjusting the luminescent properties in a number of synthesized compounds. In principle, the article is worthy of publication, but there are a number of comments to it. 

1. It is necessary to reduce the level of self-citation to an appropriate level.
2. UV absorption spectra should be accompanied by calculated extinction coefficients.
3. The excitation spectra must be given for all compounds.
4. It is necessary to provide a table with structural characteristics although in SI.
5. The same applies to the full table with the X-ray experiment parameters.
6. SI also needs to be supplemented with full IR spectra, including an area up to 4000 cm^-1.
7. Data 1H and 13C are missing in the paper.

Author Response

Reviewer 2

Comments and Suggestions for Authors

The presented work describes the synthesis of nitrogen-containing heterocyclic ligands and zinc complexes based on them. The obtained compounds demonstrate luminescent properties. The authors tried to understand the possibilities of adjusting the luminescent properties in a number of synthesized compounds. In principle, the article is worthy of publication, but there are a number of comments to it.

 

• It is necessary to reduce the level of self-citation to an appropriate level.

 

We thank the referee for the suggestion. The level of self-citations is in line with the publisher’s guidelines. Moreover, we would like to emphasize that this work focuses on a research subject (imidazo[1,5-a]pyridine ligands) that is still poorly explored and investigated by only a few research groups. In fact, all known groups working in this field have been represented in the references. The first author, who has authored three different reviews focused on imidazopyridines and specifically on imidazo[1,5-a]pyridines, has selected the most relevant and recent studies concerning the use of these ligands for the preparation of luminescent complexes.

In the revised version of the manuscript, several new references have been added, thereby modifying the self-citation rate highlighted by the referee.

 

 

• UV absorption spectra should be accompanied by calculated extinction coefficients.

We thank the referee for the comment. Unfortunately, the very low solubility of the obtained complexes prevents the reproducible preparation of concentrated solutions with an exact concentration (stock solutions or mother solutions to create more dilute solutions). This is the same issue that hinders the acquisition of NMR spectra and the growth of suitable single crystals. This limitation is well known for this class of Zn(II) imidazopyridine complexes and is shared by other researchers working in this field. Indeed, the requested data are typically absent in their publications as well. See references 16, 17, 25, 32 in the manuscript.

 

• The excitation spectra must be given for all compounds.

We thank the referee for the suggestion. In the revised version of the manuscript, all excitation spectra have been added to the Supporting Information (see Figures S8–S15).

 

• It is necessary to provide a table with structural characteristics although in SI.

We thank the referee for the suggestion. All the requested data are now available in the Supporting Information, as requested.

 

• The same applies to the full table with the X-ray experiment parameters.

We thank the referee for the suggestion. All the requested data are now available in the Supporting Information, as requested.

 

• SI also needs to be supplemented with full IR spectra, including an area up to 4000 cm^-1.

We thank the referee for the suggestion. All the requested data are now available in the Supporting Information, as requested.

 

 

• Data 1H and 13C are missing in the paper.

We thank the referee for the comment. The ligands reported in this work have been previously published, and their NMR data are available in the references indicated for each ligand in Section 2.1. As for the complexes, it is not possible to obtain NMR data due to their poor solubility in the available deuterated solvents. This limitation is well accepted and documented in the literature (see references 10,19,27,30 in the manuscript ). In this regard, the following sentence has been added in Section 2.1:"Due to the extremely low solubility of these complexes in the common deuterated solvents, it was not possible to perform NMR characterization.”

Author Response File: Author Response.docx

Reviewer 3 Report

Comments and Suggestions for Authors

1. The term "tuning" is usually employed when it is possible to modify the excitation and/or emission spectra of a material by several tens (of nanometers) through structural and/or chemical changes, which is not the case in the present study. First, the authors must provide the CIE coordinates of the different synthesized molecules, and the diagram will show that all systems are centered in the blue region and very close to each other. It might be interesting to calculate the color purity

2. In this type of study, a macroscopic photograph of the synthesized samples under the excitation source is always useful.

3. There is no explanation of the effect of Zn on the quantum yield. It is clear that it should be due to the increased "rigidity" of the structure, but this needs to be explained.

4. It is evident that the XRD spectra of the synthesized samples are necessary. Without these results, the structural characterization is incomplete and highly speculative, as Raman alone is not sufficient to confirm that the mentioned structures were obtained.

5. The authors overlook a fundamental aspect in this type of compounds: morphology, since it is well known that different morphologies can also cause shifts in the emission bands of various complexes. At the very least, this issue should be mentioned in the text if proper morphological studies cannot be conducted.

6. What is the yield of the synthesis reactions for the compounds?

7. These types of materials are not natural candidates for bioimaging applications due to the need for UV excitation.

8. The effect of Cl₂ as a ligand is not explained in detail.

Author Response

Reviewer 3

Comments and Suggestions for Authors

1. The term "tuning" is usually employed when it is possible to modify the excitation and/or emission spectra of a material by several tens (of nanometers) through structural and/or chemical changes, which is not the case in the present study. First, the authors must provide the CIE coordinates of the different synthesized molecules, and the diagram will show that all systems are centered in the blue region and very close to each other. It might be interesting to calculate the color purity.

We thank the referee for the observation. The term "tuning" is commonly used in studies that explore the correlation between chemical structure and emission properties, even when referring solely to the emission or absorption maximum of the investigated species. It is also widely employed in the titles of articles whose focus—similarly to the present manuscript—concerns the variation of chemical groups, symmetry, metal center, and the resulting optical properties. For this reason, the authors would prefer not to modify the text, leaving the final decision on the appropriateness of the term to the editor. A few examples of articles where the term is used in a similar context are provided below.

1. Ardizzoia, G.A.; Brenna, S.; Durini, S.; Therrien, B.; Veronelli, M. Synthesis, Structure, and Photophysical Properties of Blue-Emitting Zinc(II) Complexes with 3-Aryl-Substituted 1-Pyridylimidazo[1,5- a ]Pyridine Ligands: Blue-Emitting Zinc(II) Complexes. European Journal of Inorganic Chemistry 2014, 2014, 4310–4319, doi:10.1002/ejic.201402415.
2. Volpi, G.; Priola, E.; Garino, C.; Daolio, A.; Rabezzana, R.; Benzi, P.; Giordana, A.; Diana, E.; Gobetto, R. Blue Fluorescent Zinc(II) Complexes Based on Tunable Imidazo[1,5-a]Pyridines. Inorganica Chimica Acta 2020, 509, 119662, doi:10.1016/j.ica.2020.119662.
3. Cerrato, V.; Volpi, G.; Priola, E.; Giordana, A.; Garino, C.; Rabezzana, R.; Diana, E. Mono-, Bis-, and Tris-Chelate Zn(II) Complexes with Imidazo[1,5-a]Pyridine: Luminescence and Structural Dependence. Molecules 2023, 28, 3703, doi:10.3390/molecules28093703.
4. Ardizzoia, G.A.; Colombo, G.; Therrien, B.; Brenna, S. Tuning the Fluorescence Emission and HOMO-LUMO Band Gap in Homoleptic Zinc(II) Complexes with N,O-Bidentate (Imidazo[1,5-a]Pyrid-3-Yl)Phenols. European Journal of Inorganic Chemistry 2019, 2019, 1825–1831, doi:10.1002/ejic.201900067.
5. Reviglio, C.; Volpi, G.; Wyart, E.; Ciubini, B.; Prandi, C.; Barolo, C.; Porporato, P.E.; Garino, C. Imidazopyridines as Fluorogenic Substrates for Esterase Detection. Journal of Photochemistry and Photobiology A: Chemistry 2025, 462, 116256, doi:10.1016/j.jphotochem.2024.116256.

 

1. In this type of study, a macroscopic photograph of the synthesized samples under the excitation source is always useful.

We thank the referee for the suggestion. In the revised version, images of the obtained products have been added to the Supporting Information (see Figure S6. Photographs of the obtained complexes in the solid state (powder): under ambient light (top) and under UV illumination at 254 nm (bottom).

1. There is no explanation of the effect of Zn on the quantum yield. It is clear that it should be due to the increased "rigidity" of the structure, but this needs to be explained.

We thank the referee for the comment. The increase in quantum yield and, more generally, the enhancement of the optical properties of the studied imidazopyridine ligands upon complexation has already been reported in detail in previous works (e.g., Cerrato, V.; Volpi, G.; Priola, E.; Giordana, A.; Garino, C.; Rabezzana, R.; Diana, E. Mono-, Bis-, and Tris-Chelate Zn(II) Complexes with Imidazo[1,5-a]Pyridine: Luminescence and Structural Dependence. Molecules 2023, 28, 3703, doi:10.3390/molecules28093703), and for this reason, they have not been discussed in the present study. To clarify this point, the following sentence has been added in Section 2.2. : “As previously reported, an intense increase in the quantum yield is appreciable after the complexation reaction of an imidazo[1,5-a]pyridine-based ligand with Zn(II), due to an important modification of the ligand conformation.[24]”

In general, for imidazopyridine systems, coordination involves the restriction of the rotation of the pendant pyridine at position 1, which participates in the coordination bond, and a modification of its angle relative to the imidazopyridine core. These aspects have been analyzed and highlighted in the articles cited in the manuscript. Ultimately, this increase in rigidity and structural strain leads to the enhanced quantum yield observed in the various cases.

1. It is evident that the XRD spectra of the synthesized samples are necessary. Without these results, the structural characterization is incomplete and highly speculative, as Raman alone is not sufficient to confirm that the mentioned structures were obtained.

We understand that a complete structural analysis can give a further confirmation of the formation of the complexes, but we did not obtained crystals suitable for SC-XRD analysis, due to the low solubility of the products in the numerous tried solvents. In our opinion the analysis of vibrational spectra can confirm the complexation. In previous works we performed a complete vibrational assignment of different imidazo-pyridine, that allows a detailed analysis of the vibrational modes. The observed shifts of the band of ligands discussed in the text are analogous to those observed for similar complexes (with known structures) that we studied in the past. The analysis of FIR region also supports the formation of the complexes, due the significant shift of Zn-Cl mode with respect to ZnCl2 and to evidence this feature a figure was added in SI. The signal related to Zn-N mode is very weak, but it is still recognizable at 230 cm-1, a value very similar to those observed for similar systems (zinc halide complexes with bipy).

The authors emphasize that the combination of the provided analyses (emission, vibrational, and mass spectrometry) confirms the proposed structures, and that all ligands have been previously published and characterized. The coordination of Zn(II) with the employed ligands is consistent and corresponds to similar complexes already reported in the literature. This study focuses on the variation of optical properties in solution for complexes with different symmetry and multiplicity; however, the coordination model of Zn(II) with N–N imidazopyridine-type ligands is well established in the literature.

1. The authors overlook a fundamental aspect in this type of compounds: morphology, since it is well known that different morphologies can also cause shifts in the emission bands of various complexes. At the very least, this issue should be mentioned in the text if proper morphological studies cannot be conducted.

We thank the referee for this insightful comment. As outlined in the manuscript, the present study focuses on the characterization of the compounds in solution and on the correlation between chemical structure and optical properties. While we acknowledge that morphology can significantly affect solid-state emission, such investigation falls outside the scope of this work. Nevertheless, the suggestion is highly valuable, especially considering the promising photophysical results obtained in solution. We agree that a detailed morphological analysis could be an important aspect to explore in future studies aimed at developing solid-state devices or materials based on these complexes.

6. What is the yield of the synthesis reactions for the compounds?

We thank the referee for the suggestion. The detailed synthetic procedure, including the reaction yields of the newly obtained products, has been added to the Supporting Information. For the previously published compounds, reference is made to the articles cited in the bibliography.

1. These types of materials are not natural candidates for bioimaging applications due to the need for UV excitation.

We thank the referee for the comment. Although UV excitation can represent a limitation in some bioimaging contexts, several fluorescent probes reported in the literature are effectively excited in the UV region and are still widely employed for cellular and in vitro imaging. The studied Zn(II) complexes exhibit intense emission in the visible range (440–480 nm) with quantum yields up to 37%, making them suitable for fluorescence-based detection. Moreover, their structural modularity allows for future tuning of the absorption profile toward longer wavelengths. For these reasons, we consider them promising candidates for bioimaging applications.

Several commercially available and widely used fluorophores are efficiently excited in the UV region, including DAPI (absorption ~358 nm), Hoechst dyes such as Hoechst 33258 and 33342 (absorption ~350–360 nm), and quinine sulfate (absorption ~320–340 nm). These compounds are routinely employed in bioimaging and fluorescence-based assays, particularly for nuclear staining or as quantum yield standards, demonstrating that UV-excitable fluorophores remain relevant and practical in various biological applications.

Moreover, some of the authors involved in this manuscript have recently published a bioimaging study using functionalized imidazopyridines with absorption properties very similar to those of the complexes reported here (see: Reviglio, C.; Volpi, G.; Wyart, E.; Ciubini, B.; Prandi, C.; Barolo, C.; Porporato, P.E.; Garino, C. Imidazopyridines as Fluorogenic Substrates for Esterase Detection. Journal of Photochemistry and Photobiology A: Chemistry 2025, 462, 116256, doi:10.1016/j.jphotochem.2024.116256.).

1. The effect of Cl₂ as a ligand is not explained in detail.

The role of Cl⁻ as a ligand in Zn(II) complexes, and in particular in complexes with imidazopyridine ligands, has not been discussed in this work because it has already been thoroughly addressed in previous publications. Specifically, the following studies focus on the properties of coordinating anions in zinc complexes with imidazopyridines.

1. Ardizzoia, G.A.; Brenna, S.; Durini, S.; Therrien, B.; Veronelli, M. Synthesis, Structure, and Photophysical Properties of Blue-Emitting Zinc(II) Complexes with 3-Aryl-Substituted 1-Pyridylimidazo[1,5- a ]Pyridine Ligands: Blue-Emitting Zinc(II) Complexes. European Journal of Inorganic Chemistry 2014, 2014, 4310–4319, doi:10.1002/ejic.201402415.
2. Cerrato, V.; Volpi, G.; Priola, E.; Giordana, A.; Garino, C.; Rabezzana, R.; Diana, E. Mono-, Bis-, and Tris-Chelate Zn(II) Complexes with Imidazo[1,5-a]Pyridine: Luminescence and Structural Dependence. Molecules 2023, 28, 3703, doi:10.3390/molecules28093703.
3. Ardizzoia, G.A.; Brenna, S.; Durini, S.; Therrien, B. Synthesis and Characterization of Luminescent Zinc(II) Complexes with a N,N-Bidentate 1-Pyridylimidazo[1,5-a]Pyridine Ligand. Polyhedron 2015, 90, 214–220, doi:10.1016/j.poly.2015.02.005.

To acknowledge these works, the following sentence has been added to Section 2.1 of the manuscript: "ZnCl₂ was selected as the starting reagent due to the presence of Cl⁻ as a stable counterion and coordinating ligand, as previously reported."

Author Response File: Author Response.docx

Round 2

Reviewer 2 Report

Comments and Suggestions for Authors

The authors have corrected the shortcomings and responded to all comments. The paper may be accepted.

Reviewer 3 Report

Comments and Suggestions for Authors

The authors improved the manuscript, and it can be accepted.