Supramolecular Organic and Organometallic Chemistry Centre

Abstract
The goal of this proposal is to obtain new organochalcogen compounds and metal complexes which can act as efficient antitumor and chemopriventive agents. Our objectives are: (i) to design organochalcogen derivatives of type R₂E₂, RR'E, R₂E (E = Se,Te; R,R' = organic groups with donor atoms capable for intra- or intermolecular interactions) and their metal (Au,Ag,Zn,Sn,Bi) complexes, with potential as antioxidant, antitumor and chemopreventive agents, (ii) to study their solution behavior and solid state structure, (iii) to assay their antitumor activity against commercial tumor cell lines, (iv) to find an optimized strategy, based on experimental evidence and theoretical approach (DFT, QSAR) for highly active species with low toxicity, (v) to investigate the relation structure-antioxidant activity-antitumor properties for selected classes of compounds and (vi) to identify the interaction mechanism at cell level. The proposed organochalcogen compounds are flexible, potential tridentate systems, containing, besides Se or Te, other functionalities (pyrazole (pz), phenylthiazole (Phtz), amino, imino, COOH, OH) which share with the central chalcogen or the metal their donation ability and the own biological properties. The chosen ligands and their metal complexes are very attractive both for fundamental research and as promising active antitumor agents. The project combines research excellence and complementarity and is essentially based on inter- and multidisciplinary studies.

Results

Stage 1 in the implementation of the project; January 2021 – December 2021
The activities developed during 2021 were dedicated to the fulfilment of the objectives proposed in the approved application (contract 220/2021), as followings:

• The synthesis and structural characterization of new organochalcogen compounds of type RR'Se (R = R' = Me₂C(OH)CH₂, 2-(Me₂NCH₂)C₆H₄, CH₂phtz, CH₂CH₂pz; R ≠ R', R = 2-(Me₂NCH₂)C₆H₄, - R' = Me₂C(OH)CH₂, (CF₃)₂C(OH)CH₂);
• The synthesis and structural characterization of new compounds of type [2,6-(Me₂NCH₂)C₆H₃]₂Se₂, 2,6–[(2–Me₂NCH₂C₆H₄)SeCH₂]₂C₅H₃N and 2,6–[(2–Et₂NCH₂C₆H₄)SeCH₂]₂C₅H₃N;
• The synthesis and structural characterization of new Au(I) and Ag(I) complexes with chalcogen donor atoms;
• The synthesis and structural characterization of new group 12 complexes with chalcogen donor atoms;
• The synthesis and structural characterization of new Sn(IV) complexes with Se→Sn interactions;
  

The obtained results were disseminated through 5 papers (2 already published and 3 under evaluation) and 10 oral or poster presentations to national and international conferences.

Stage 2 in the implementation of the project: January 2022 – December 2022
The activities developed during 2022 were dedicated to the fulfilment of the objectives proposed in the approved application (contract 220/2021), as followings:

• The synthesis and structural characterization of new homo- and heteroleptic diorganochalcogen compounds of type RR'Se (R = 2-(Me₂NCH₂)C₆H₄, 2-(Et₂NCH₂)C₆H₄, 2-[O(CH₂CH₂)NCH₂]C₆H₄; R' = CH₂phtz, CH₂CH₂pz, 2-(Me₂NCH₂)C₆H₄;
• The synthesis and structural characterization of new silver(I) complexes with homo- and heteroleptic diorganoselenium ligands;
• Solution behavior and solid state structure of the diorganoselenides and their silver complexes; coordination behavior of the RR'Se ligands;
• Studies related to the antioxidant behavior (GPx-like mimics) of the diorganoselenides in the oxidation reaction of PhSH to PhSSPh; NMR evidences for the existence of intramolecular N→Se interactions in the RR'Se=O intermediates and theoretical evaluation of the strength of these interactions by DFT calculations;
• Investigation of the antiproliferative activity of diorganoselenides and their silver(I) complexes against the melanoma B16.F10 cells;

The obtained results were disseminated in 4 papers (2 already published and 2 in preparation) and 10 oral or poster presentations to national and international conferences.

Articles

1. Silver(I) complexes based on diorganoselenium(II) ligands with amino or hydroxo functionalities,
   M. David, R. Mitea, A. Silvestru, J. Mol. Struct., 2021, 1246, 131243.
   DOI: 10.1016/j.molstruc.2021.131243
   
   
2. New mercury(II) complexes of polydentate ligands,
   C. Șalgău, A. Dobri, A. Silvestru Studia Univ. “Babes-Bolyai”, Chemia, LXVI, 2021, 3, 175-185.
   DOI: 10.24193/subbchem.2021.3.10
   
   
3. Silver(I) and gold(I) complexes of multidentate ligands based on functionalized pyridine,
   D. Dumitraș, A. Pop, A. Silvestru, Polyhedron, 2022, 220, 115801.
   DOI: 10.1016/j.poly.2022.115801
   
   
4. New ionic [{2-(Me₂NCH₂)C₆H₄}(R)Sn{(EPPh₂)₂N}][(EPPh₂)₂N] (R = 2-(Me₂NCH₂)C₆H₄, ⁿBu; E = O, S, Se) compounds. Solution behavior and solid state structure,
   E Denes, L. Marangiu, M. Arca, V. Lippolis, A. Silvestru, J. Organomet. Chem., 2022, 963, 122282.
   DOI: 10.1016/j.jorganchem.2022.122282
   
   
5. Group 12 metal complexes of mixed thia/aza and thia/oxa/aza macrocyclic ligands,
   A. M. Hodorogea, A. Silvestru, V. Lippolis, A. Pop, Polyhedron, 2022, 216, 115650.
   DOI: 10.1016/j.poly.2022.115650
   
   
6. Homoleptic and heteroleptic diorganoselenides containing pyrazole functionalities. Synthesis, characterization, and antioxidant activity,
   R. A. Popa, A. Nicoară, M. Arca, V. Lippolis, A. Pintus, A. Silvestru, Appl. Organomet. Chem., 2022, 36, e6894.
   DOI: 10.1002/aoc.6894
   
   
7. On the coordination behaviour of diorganoselenium ligands based on amino and azole functionalities: silver(I) complexes with relevance for biological applications,
   R. A. Popa, M. David, E. Licarete, M. Banciu, A. Silvestru, New J. Chem., 2022.
   DOI: 10.1039/D2NJ04812D
   
   

Conferences

1. Organochalcogen compounds with relevance for biology. Structure and reactivity,
   A. Silvestru,
   at Simpozionul cu participare internațională – Noi tendințe și strategii în chimia materialelor avansate, cu relevanță în sisteme biologice, tehnică și protecția mediului, Timișoara, October 7-8, 2021 (oral presentation).
   
   
2. Silver Complexes with Diorganochalcogen Ligands of Type (2-XC₆H₄CH₂)₂E (E = S, Se; X = Br, CH₃),
   A. L. Corjuc, A. Silvestru,
   at Zilele Academice Clujene, Cluj-Napoca, October 21-22, 2021 (oral presentation).
   
   
3. Diorganoselenides and their late d-metal complexes. Synthesis and structural characterization,
   M. David, R.-A. Popa, R. Mitea, A. Silvestru,
   at Zilele Academice Clujene, Cluj-Napoca, October 21-22, 2021 (oral presentation).
   
   
4. Novel Silver(I) Complexes of Organoselenium Ligands Bearing Organic Groups with Pendant Arms and Pyrazole or Phenylthiazole Moieties,
   R. A. Popa, A. Silvestru,
   at Zilele Academice Clujene, Cluj-Napoca, October 21-22, 2021 (oral presentation).
   
   
5. Organoselenium ligands and their silver(I) complexes. Synthesis and structural characterization,
   A.-M. Lazăr, Maria David, A. Pop,
   at 17^th International Conference Students for Students, Cluj-Napoca, April 21-23, 2021 (oral presentation).
   
   
6. Hypercoordinated organoselenium ligands and their reactivity towards group 12 metals,
   C. E. Șalgău, A. Silvestru,
   at 17^th International Conference Students for Students, Cluj-Napoca, April 21-24, 2021 (oral presentation).
   
   
7. Organoselenium pincer ligands and their reactivity towards late transition metals,
   D. Dumitraș, A. Silvestru,
   at 17^th International Conference Students for Students, Cluj-Napoca, April 21-24, 2021 (oral presentation).
   
   
8. Synthesis and structural characterization of group 11 metal complexes of [2-(Me₂NCH₂)C₆H₄]₂Se,
   M. David, A. Silvestru,
   at 17^th International Conference Students for Students, Cluj-Napoca, April 21-24, 2021 (oral presentation).
   
   
9. Group 11 metal complexes based on diorganoselenium ligands,
   M. David, R.-A. Popa,
   at Sesiunea de Comunicări Științifice Studențești, ediția a XVI-a, May 28-29, 2021 (oral presentation).
   
   
10. Structural aspects in mercury complexes with organoselenium ligands,
    C. E. Șalgău, A. Silvestru,
    at Sesiunea de Comunicări Științifice Studențești, ediția a XVI-a, May 28-29, 2021 (oral presentation).
    
    
11. Diorganoselenium ligands based on amino and azole functionalities: Synthesis, structure, coordination behaviour and relevance for biological applications,
    R.-A. Popa, E. Licarete, M. Banciu, A. Silvestru,
    at ICCBIC XXVIII, Smolenice, Slovakia, June 2022 (oral presentation).
    
    
12. Silver(I) complexes of diorganochalcogen (S, Se) ligands. Synthesis, structure and specific properties,
    A. L. Corjuc, M. David, D. Dumitraș, A. Silvestru,
    at ICCBIC XXVIII, Smolenice, Slovakia, June 2022 (oral presentation).
    
    
13. Novel silver(I) complexes of a diorganoselenium ligand with phenylthiazole functionalities. Synthesis, structure and potential applications,
    M. David, A. Silvestru,
    at 18^th International Conference Students for Students, Cluj-Napoca, April, 2022 (oral presentation).
    
    
14. Organochalcogen compounds with relevance for biology, organic synthesis and nanomaterials,
    A. Silvestru,
    at A XXXVI-a Conferință Națională de Chimie, Călimănești-Căciulata, October, 2022 (invited lecture).
    
    
15. Diorganochalcogenides with alcoxo functionalities and their silver(I) complexes,
    M. Tamas, R. Mitea, A. Silvestru,
    at A XXXVI-a Conferință Națională de Chimie, Călimănești-Căciulata, October, 2022 (poster presentation).
    
    
16. Synthesis, structural characterization and antiproliferative activity assay of a diorganoselenide ligand and its silver(I) complexes,
    M. David, A. Silvestru,
    at A XXXVI-a Conferință Națională de Chimie, Călimănești-Căciulata, October, 2022 (oral presentation).
    
    
17. Complecși de zinc și cadmiu hipercoordinați cu liganzi organoselenolato. Sinteză și caracterizare structurală,
    C. E. Șalgău, A. Pop, A. Silvestru,
    at A XXXVI-a Conferință Națională de Chimie, Călimănești-Căciulata, October, 2022 (poster presentation).
    
    
18. NMR spectroscopy – a versatile tool for GPx mimetic studies,
    R.-A. Popa, A. Silvestru,
    at CEUM 2022, Warsaw, Poland, September, 2022 (poster presentation).
    
    
19. Group 11 metal complexes of diorganoselenium ligands. Synthesis, structure and specific properties,
    A. Silvestru,
    at ICCST 15, Florianopolis, Brazil, Nov.-Dec. 2022 (invited lecture).
    
    
20. New organoselenium compounds - synthesis, structural characterization and reactivity,
    A. Pop,
    at ICCST 15, Florianopolis, Brazil, Nov.-Dec. 2022 (poster presentation).
    
    

For information about unpublished results contact Prof. Dr. Anca Silvestru at anca.silvestru@ubbcluj.ro.