Structural Insights and Intermolecular Energy for Some Medium and Long-Chain Testosterone Esters
Abstract
:1. Introduction
- (i)
- Testosterone enanthate: Androst-4-en-17β-ol-3-one 17β-heptanoate, (TEna, Figure 1b);
- (ii)
- Testosterone cypionate: Androst-4-en-17β-ol-3-one 17β-cyclopentylpropionate, (TCyp, Figure 1c);
- (iii)
- Testosterone decanoate: Androst-4-en-17β-ol-3-one 17β-decanoate, (TDec, Figure 1d);
- (iv)
- Testosterone undecanoate: Androst-4-en-17β-ol-3-one 17β-undecanoate, (TUnd, Figure 1e).
2. Results
2.1. Crystal Structures Analysis
2.1.1. TEna (Testosterone Enanthate)
2.1.2. TCyp (Testosterone Cypionate)
2.1.3. TDec (Testosterone Decanoate)
2.1.4. TUnd (Testosterone Undecanoate)
- (i)
- All four esters crystallize in various non-centrosymmetric monoclinic and orthorhombic space groups;
- (ii)
- (iii)
- Although C-H⋯O interactions participate in the formation of supramolecular 3D assemblies, their weight is quite small compared to dispersion effects (see the crystal energies analysis section);
- (iv)
- C-H⋯O bonds are characterized by hydrogen⋯carbonyl donor-acceptor distances (Table S3, Supplementary Materials), which fall into the same range as other structures of the steroid class [26,27,28,29];
- (v)
- The six membered A rings depict an intermediate sofa-half-chair conformation, B and C exhibit chair geometry, and the five membered D backbone rings display an intermediate envelope-half-chair geometry. The C17 methylated form [30] and other short esters have been shown to possess similar geometries [16,18].
2.2. Crystal Lattice Energies Evaluation
2.3. Intermolecular Energies Evaluation
- (i)
- Since the crystalline structures do not possess classic strong hydrogen bonds but C-H⋯O interactions, the electrostatic terms have small values in all cases;
- (ii)
- The values of the polarization energies are very low, which indicates that the molecules are not polarized;
- (iii)
- The values of the total energies are relatively low and vary in a wide range (−10.4 to −60.8 kJ/mol) due to the different orientations of the molecules relative to each other; between the neighboring molecules, there are rather weak interactions due to the lack of strong hydrogen bonds;
- (iv)
- Table S4 (Supplementary Materials) shows that the dispersion energy is dominant.
2.4. Hirshfeld Surfaces and Fingerprint Plots Analysis
- (i)
- Fingerprint plots of esterified forms (Figure S3, Supporting Information) are asymmetric, which is characteristic of crystals with two or more molecules in the asymmetric unit and appears as a result of a distinct molecular environment in crystal;
- (ii)
- The plots are illustrating H⋯O/O⋯H spikes, which denote the existence of C-H⋯O hydrogen bonds, but for TDec the H⋯O/O⋯H spikes are less protruding as a consequence of longer distances in the C-H⋯O bonds, which are closer to the sum of vdW radii;
- (iii)
- A quantitative breakdown of fingerprint diagrams (Table S2, Supplementary Materials) shows the similarities in individual contributions in all four esters, with the highest percentage in H⋯H contacts, followed by a medium percentage of O⋯H/H⋯O intercontacts and a smaller one for C⋯H/H⋯C, respectively;
- (iv)
- Based on the large percentages of H⋯H contacts for all crystals (fingerprint breakdown in Table S2, Supplementary Materials) corroborated crystal and intermolecular energies (Table 2 and Table S4 from Supplementary Materials) validate that dispersion components play the major role in overall packing.
2.5. Solubility Evaluation
2.6. FT-IR Spectroscopy Analysis
2.7. DTA/TG Analysis
3. Materials and Methods
3.1. Materials and Recrystallization Experiments
3.2. Powder X-ray Diffraction
3.3. Single Crystal X-ray Diffraction and Structures Refinement
3.4. Computational Methods
3.5. Solubility Evaluation
3.6. FT-IR Spectroscopy
3.7. Differential Thermal Analysis (DTA) and Thermogravimetric Analysis (TG)
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Identification Code | TEna | TCyp | TDec | TUnd |
---|---|---|---|---|
Empirical formula | C26H40O3 | C27H40O3 | C29H46O3 | C30H48O3 |
Formula weight | 400.58 | 411.58 | 442.66 | 456.68 |
Temperature/K | 293(2) | 293(2) | 293(2) | 293(2) |
Crystal system | monoclinic | orthorhombic | orthorhombic | monoclinic |
Space group | P21 | P21212 | P212121 | P21 |
a/Å | 10.5644(6) | 20.9920(6) | 8.3367(3) | 10.5820(2) |
b/Å | 8.2875(6) | 32.0578(8) | 19.0481(6) | 8.23950(10) |
c/Å | 27.6918(15) | 7.2292(2) | 33.7169(12) | 32.3890(4) |
α/° | 90 | 90 | 90 | 90 |
β/° | 94.652(5) | 90 | 90 | 99.3530(10) |
γ/° | 90 | 90 | 90 | 90 |
Volume/Å3 | 2416.5(3) | 4864.9(2) | 5354.2(3) | 2786.47(7) |
Z | 4 | 8 | 8 | 4 |
ρcalc g/cm3 | 1.101 | 1.124 | 1.098 | 1.089 |
μ/mm−1 | 0.542 | 0.553 | 0.531 | 0.523 |
F(000) | 880.0 | 1800.0 | 1952.0 | 1008.0 |
Radiation | CuKα (λ = 1.54184) | CuKα (λ = 1.54184) | CuKα (λ = 1.54184) | CuKα (λ = 1.54184) |
2Θ range/° | 6.404 to 141.12 | 6.938 to 145.1 | 7.002 to 148.164 | 8.3 to 141.722 |
Index ranges | −12 ≤ h ≤ 12, −10 ≤ k ≤ 9, −33 ≤ l ≤ 26 | −25 ≤ h ≤ 25, −38 ≤ k ≤ 36, −7 ≤ l ≤ 8 | −8 ≤ h ≤ 10, −23 ≤ k ≤ 23, −41 ≤ l ≤ 41 | −12 ≤ h ≤ 12, −10 ≤ k ≤ 9, −39 ≤ l ≤ 39 |
Reflections collected | 15,913 | 32,749 | 75,177 | 40,701 |
Independent reflections | 8094 [Rint = 0.0422, Rsigma = 0.0471] | 9217 [Rint = 0.0620, Rsigma = 0.0556] | 10,249 [Rint = 0.1805, Rsigma = 0.0748] | 10,192 [Rint = 0.0333, Rsigma = 0.0213] |
Data/restraints/parameters | 8094/1/529 | 9217/0/545 | 10,249/0/583 | 10,192/1/601 |
Goodness-of-fit on F2 | 1.001 | 1.031 | 1.085 | 1.044 |
Final R indexes [I>=2σ (I)] | R1 = 0.0549, wR2 = 0.1372 | R1 = 0.0706, wR2 = 0.1833 | R1 = 0.0938, wR2 = 0.1762 | R1 = 0.0428, wR2 = 0.1141 |
Final R indexes [all data] | R1 = 0.0896, wR2 = 0.1652 | R1 = 0.1199, wR2 = 0.2265 | R1 = 0.1406, wR2 = 0.2100 | R1 = 0.0462, wR2 = 0.1186 |
Largest diff. peak/hole/e Å−3 | 0.15/−0.18 | 0.25/−0.17 | 0.16/−0.22 | 0.17/−0.21 |
Flack parameter | −0.21(17) | 0.04(18) | −0.02(16) | −0.09(8) |
Structure | Molar Mass g/mol | Ecoul (kJ/mol) | Epol (kJ/mol) | Edisp (kJ/mol) | Erep (kJ/mol) | Elatt (kJ/mol) |
---|---|---|---|---|---|---|
TBas | 288.43 | −33/3 | −47.5 | −130.9 | 60.9 | −150.8 |
TAce | 330.46 | −15.5 | −55.0 | −126.1 | 37.1 | −159.5 |
TPro | 344.49 | −18.3 | −55.5 | −126.4 | 33.9 | −166.3 |
TIso | 386.57 | −21.3 | −57.7 | −141.9 | 52.7 | −168.2 |
TPhp | 420.59 | −19.3 | −52.3 | −149.0 | 36.1 | −184.5 |
TEna | 400.60 | −22.5 | −60.4 | −157.4 | 64.6 | −175.7 |
TCyp | 412.61 | −17.6 | −58.5 | −142.8 | 37.0 | −181.9 |
TDec | 442.68 | −17.4 | −70.4 | −167.3 | 40.1 | −215.1 |
TUnd | 456.71 | −19.6 | −73.0 | −175.4 | 47.3 | −220.7 |
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Turza, A.; Pascuta, P.; Mare, L.; Borodi, G.; Popescu, V. Structural Insights and Intermolecular Energy for Some Medium and Long-Chain Testosterone Esters. Molecules 2023, 28, 3097. https://doi.org/10.3390/molecules28073097
Turza A, Pascuta P, Mare L, Borodi G, Popescu V. Structural Insights and Intermolecular Energy for Some Medium and Long-Chain Testosterone Esters. Molecules. 2023; 28(7):3097. https://doi.org/10.3390/molecules28073097
Chicago/Turabian StyleTurza, Alexandru, Petru Pascuta, Liviu Mare, Gheorghe Borodi, and Violeta Popescu. 2023. "Structural Insights and Intermolecular Energy for Some Medium and Long-Chain Testosterone Esters" Molecules 28, no. 7: 3097. https://doi.org/10.3390/molecules28073097