The tris(2-aminoethyl)amine molecule is a flexible tripodal structure with three aminoethyl groups. The succinic acid groups extend the flexibility of the scaffold and provide terminal carboxylates for attachment of peptide chains.

Tris(2-Aminoethyl)Amine/Metal Oxides Hybrid Materials

Three different metal oxides (basic MgO, basic-acidic Al2O3 and acidic-basic Nb2O5) characterized by comparable surface areas and pore systems (domination of mesopores with narrow pore size distribution) were modified with tris(2-aminoethyl)amine (TAEA) via two methods: (i) direct anchoring of amine on metal oxide and (ii) anchoring of amine on metal oxide functionalized with (3-chloropropyl)trimethoxysilane. It was evidenced that acidic-basic properties of metal oxides as well as the procedure of modification with tris(2-aminoethyl)amine determined the ways of amine anchoring and the strength of its interaction with the support. The obtained hybrid materials were tested in Knoevenagel condensation between furfural and malononitrile. The catalysts based on MgO showed superior activity in this reaction. It was correlated with the way of TAEA anchoring on basic MgO and the strength of modifier anchoring on the support. To the best of our knowledge tris(2-aminoethyl)amine has not been used as a modifier of solid supports for enhancement of the catalyst activity in Knoevenagel condensation.[1]

The aim of this study was to establish the effect of acid-base properties of metal oxides used as supports for tris(2-aminoethyl)amine (TAEA) on the forms of TAEA anchored and activity in Knoevenagel condensation between furfural and malononitrile. Three different commercial metal oxides (MgO, Al2O3, Nb2O5) expected to show different acid-base properties were applied for anchoring of TAEA by the use of one step direct modification and two-step TAEA loading after functionalization of metal oxides with (3-chloropropyl)trimethoxysilane (ClPTMS).The catalysts based on hybrid materials containing MgO, Al2O3 and Nb2O5 as supports and tris(2-aminoethyl)amine as an active ingredient were synthesized and characterized in details. For Nb2O5 support two different species were postulated to be formed after tris(2-aminoethyl)amine anchoring on ClPTMS functionalized niobia, one anchored to ClPTMS bonded to the solid surface and the second formed in the interaction between LAS (niobium cations) on niobia surface and TAEA.

Tris(2-aminoethyl)amine) as?An Effective Scaffold

A new scaffold, TREN-(suc-OH)3 where TREN is tris(2-aminoethyl)amine and suc is the succinic acid spacers, was incorporated to assemble triple helices composed of Gly-Nleu-Pro sequences (Nleu denotes N-isobutylglycine). Extensive biophysical studies which include denaturation studies, CD and NMR spectroscopy, and molecular modeling demonstrated that TREN-[suc-(Gly-Nleu-Pro)n-NH2]3 (n = 5 and 6) form stable triple helical structures in solution. A comparative analysis of TREN-assembled and KTA-assembled collagen mimetics (KTA denotes Kemp triacid, 1,3,5-trimethylcyclohexane-1,3,5-tricarboxylic acid) indicates that the flexibility of the TREN scaffold is superior to the KTA scaffold in inducing triple helicity. This effect most likely arises from the flexibility of the tris(2-aminoethyl)amine scaffold which allows the three peptide chains to adjust their register for a tighter triple helical packing.In our efforts toward the design of novel collagen mimetics, we expanded our scaffold studies to include a flexible scaffold. Similar to KTA-assembled structures, we synthesized a TREN (tris(2-aminoethyl)amine) scaffold, attached a series of collagen mimetic structures composed of Gly-Nleu-Pro sequences, and assessed their triple helical propensities by thermal denaturation and CD spectroscopy as well as by NMR spectroscopy and molecular modeling. In the present study, we show that the TREN scaffold, though flexible, enhances triple helicity over that of the KTA scaffold.[2]

Incidentally, while functionalization for further development of macromolecular arrays cannot be achieved readily for KTA-assembled triple helices, the tertiary amine core of the tris(2-aminoethyl)amine can be derivatized to create structural assemblies via complexation or quarternization. Further insight into the relationship between the TREN scaffold and triple helix conformations can be obtained from the differences in the methylene chemical shifts of the core tris(2-aminoethyl)amine molecule (see NMR spectra in the Supporting Information). At high temperature (T = 50 °C), only two distinguishable resonances at 3.50 and 3.27 ppm were observed for TREN-[suc-(Gly-Nleu-Pro)5-NH2]3, indicating spectral overlap of the six methylene groups from the three chains. This overlap results from the rotational ternary symmetry of the TREN structure. At T = 4 °C, the triple helix for the TREN-[suc-(Gly-Nleu-Pro)5-NH2]3 is favored, and a signal splitting of these resonances was observed. Hence, the rotational three-fold symmetry of the tris(2-aminoethyl)amine template is disrupted by the triple helical register (screw symmetry). The comparison of the two scaffolds by CD and NMR spectroscopy and molecular modeling indicate that the flexibility of the tris(2-aminoethyl)amine molecule enhances triple helicity over that of the more rigid KTA molecule.

References

[1]Stawicka K, Ziolek M. Tris(2-Aminoethyl)Amine/Metal Oxides Hybrid Materials-Preparation, Characterization and Catalytic Application. Molecules. 2020 Oct 14;25(20):4689. doi: 10.3390/molecules25204689. PMID: 33066391; PMCID: PMC7587344.

[2]Kwak J, De Capua A, Locardi E, Goodman M. TREN (Tris(2-aminoethyl)amine): an effective scaffold for the assembly of triple helical collagen mimetic structures. J Am Chem Soc. 2002 Nov 27;124(47):14085-91. doi: 10.1021/ja0209621. PMID: 12440907.