Synthesis, spectral characterization and in vitro antibacterial evaluation and Petra/Osiris/Molinspiration analyses of new Palladium(II) iodide complexes with thioamides

Peer review under responsibility of Alexandria University Faculty of Medicine.

Figures & data

Scheme 1 Structures of the ligands used for complexation.

Scheme 2 General reaction for the synthesis of the complexes.

Table 1 Proposed structure of the synthesized compounds.

Comp. code	Structure	Comp. code	Structure
[Pd(Dmtu)4]I2		[Pd(Imt)4]I2
[Pd(Metu)4]I2		[Pd(Mpy)4]I2
[Pd(Dmtu)4]I2		[Pd(Mpm)4]I2
[Pd(Tmtu)4]I2		[Pd(Tna)4]I2

Table 2 CHNS analysis, and MP of [Pd(L)₄]I₂ complexes.

Compound	Color	Found (calculated) %				MP (°C)
		C	H	N	S
[Pd(Tu)4]I2	Dark brown	7.20 (7.22)	2.23 (2.41)	16.31 (16.85)	9.57 (9.63)	248–249
[Pd(Metu)4]I2	Pale yellow	13.41 (13.32)	3.36 (3.33)	15.62 (15.54)	8.90 (8.88)	214–216
[Pd(Dmtu)4]I2	Dark brown	18.48 (18.53)	4.10 (4.12)	14.39 (14.42)	8.21 (8.24)	202–204
[Pd(Tmtu)4]I2	Dark brown	27.01 (26.98)	5.42 (5.40)	12.57 (12.59)	7.21 (7.19)	245–247
[Pd(Imt)4]I2	Dark brown	18.75 (18.73)	3.15 (3.12)	14.51 (14.57)	8.33 (8.32)	242–244
[Pd(Mpy)4]I2	Dark brown	29.86 (29.82)	2.51 (2.48)	6.94 (6.96)	7.91 (7.95)	199–202
[Pd(Mpm)4]I2	Dark red	23.71 (23.74)	2.00 (1.98)	13.87 (13.85)	7.89 (7.91)	253–255
[Pd(Tna)4]I2	Dark brown	31.58 (31.56)	2.68 (2.63)	12.31 (12.27)	7.04 (7.01)	193–195

Table 3 Selected IR absorption (cm⁻¹) for free ligands and their Palladium(II) iodide complexes.

Compound	ν(C=S)	ν(N–H)	ν(N–H)	ν(C–N)	ν(Pd–S)	ν(Pd–I)
Tu	730	3156, 3365	1604	1473	–	–
[Pd(Tu)4]I2	706	3176, 3379	1608	1384	327	270
Metu	634	3163, 3245	1624	1488	–	–
[Pd(Metu)4]I2	762	3176	1619	1469	328	279
Dmtu	641	3203	1552	1521	–	–
[Pd(Dmtu)4]I2	717	3283, 3340	1573	1492	324	260
Tmtu	622	–	–	1491	–	–
[Pd(Tmtu)4]I2	675	2923, 3468	1553	1493	335	279
Imt	510	3200	1499	1307	–	–
[Pd(Imt)4]I2	562	3306	1507	1317	317	273
Mpy	613	3176	1578	1487	–	–
[Pd(Mpy)4]I2	754	2917, 3064	1498	1573	304	269
Mpm	624	3053	1602	1491	–	–
[Pd(Mpm)4]I2	748	3032	1525	1567	301	272
Tna	699	3180	1675	1455	–	–
[Pd(Tna)4]I2	671	3136, 3278	1613	1464	304	265

Table 4 ¹H NMR data of the ligands and their Palladium(II) iodide complexes.^a

Compound	NH2	NH	H-2	H-3	H-4	H-5	H-6	N–CH3
Tu	7.06, s	–	–	–	–	–	–	–
[Pd(Tu)4]I2	7.88, s	–	–	–	–	–	–	–
Metu	7.45, s	7.60, s	–	–	–	–	–	2.80, s
[Pd(Metu)4]I2	8.63, s	7.65, s	–	–	–	–	–	2.82, s
Dmtu	–	7.38, s	–	–	–	–	–	2.81, s
[Pd(Dmtu)4]I2	–	8.51, s	–	–	–	–	–	2.84, 2.90, s
Tmtu	–	–	–	–	–	–	–	3.08, s
[Pd(Tmtu)4]I2	–	–	–	–	–	–	–	3.11, s
Imt	–	7.99, s	3.62, d	–	–	–	–	–
[Pd(Imt)4]I2	–	8.96, s	3.90, d	–	–	–	–	–
Mpy	–	10.12, s	7.53, d	7.40, d	7.90, t	7.23, d	–	–
[Pd(Mpy)4]I2	–	10.21, s	7.57, d	7.45, d	7.99, t	7.25, d	–	–
Mpm	–	8.28, t	8.30, d	–	8.20, d	–	–	–
[Pd(Mpm)4]I2	–	8.97, t	8.36, d	–	8.24, d	–	–	–
Tna	9.12, s	10.12, s	–	7.90, t	7.60, t	8.23, d	7.16, s	–
[Pd(Tna)4]I2	9.16, s	10.21, s	–	7.95, t	7.69, t	8.25, d	7.20, s	–

a Numbering is in accordance with Scheme 1.

Table 5 ¹³C NMR data of the ligands and their Palladium(II) iodide complexes. ^a

Compound	C-1	C-2	C-3	C-4	C-5	C-6
Tu	183.8	–	–	–	–	–
[Pd(Tu)4]I2	178.06	–	–	–	–	–
Metu	181.3	31.1	–	–	–	–
[Pd(Metu)4]I2	175.5	32.4	–	–	–	–
Dmtu	183.0	30.7	–	–	–	–
[Pd(Dmtu)4]I2	174.9	31.03	–	–	–	–
Tmtu	193.4	42.1	–	–	–	–
[Pd(Tmtu)4]I2	187.1	44.7	–	–	–	–
Imt	183.9	44.0	–	–	–	–
[Pd(Imt)4]I2	178.4	45.4	–	–	–	–
Mpy	177.7	133.2	113.9	137.5	137.9	–
[Pd(Mpy)4]I2	167.57	132.3	120.0	139.4	140.3	–
Mpm	181.9	155.0	154.8	110.0	–	–
[Pd(Mpm)4]I2	172.9	159.3	158.2	116.4	–	–
Tna	198.0	135.0	135.3	123.1	147.6	151.6
[Pd(Tna)4]I2	194.9	136.4	137.6	126.2	141.8	148.0

a Numbering is in accordance to the Scheme 1.

Table 6 Antibacterial activity of the ligands and their Palladium(II) iodide complexes.

(% Zone of inhibition of Std. Drugs, Ligands and Complexes)
Compound	Staphylococcus aureus	Bacillus subtilis	Escherichia coli	Pseudomonas aeruginosa
	% value	% value	% value	% value
Imipenem	100 (21 mm)	100 (18 mm)	100 (16 mm)	100 (18 mm)
Tu	0	0	13	0
[Pd(Tu)4]I2	43	45	57	17
Metu	0	17	45	33
[Pd(Metu)4]I2	14	17	13	33
Dmtu	10	11	13	11
[Pd(Dmtu)4]I2	0	0	6	0
Tmtu	0	11	0	0
[Pd(Tmtu)4]I2	10	17	13	22
Imt	0	22	38	28
[Pd(Imt)4]I2	14	22	0	17
Mpy	52	95	100	83
[Pd(Mpy)4]I2	14	39	44	50
Mpm	19	45	63	45
[Pd(Mpm)4]I2	48	56	69	67
Tna	0	0	19	0
[Pd(Tna)4]I2	33	0	0	0

Table 7 Osiris calculations of toxicity risks and drug-score of the selected compounds.

Compound #	Toxicity risks				Bioavailability and drug-score
	Mutagenic	Tumorigenic	Irritant	Reproductive effective	cLog P	Solubility	TPSA	Druglikeness	Drug-score
[Pd(Dmtu)4]I2	++	++	++	++	−1.05	−1.97	52.04	−2.72	0.18
[Pd(Imt)4]I2	++	++	++	++	−1.05	−1.97	52.04	−2.72	0.18
[Pd(Metu)4]I2	++	++	++	++	−0.35	−1.08	24.06	−0.87	0.21
[Pd(Mpy)4]I2	++	++	++	++	0.18	−1.08	6.48	−4.23	0.16
[Pd(Mpm)4]I2	++	++	++	++	−0.32	−1.95	24.06	−0.20	0.23
[Pd(Tmtu)4]I2	++	++	++	++	−0.28	−3.13	12.03	−1.06	0.19
[Pd(Tu)4]I2	++	++	++	++	−0.13	−2.72	24.39	−0.83	0.20
[Pd(Tna)4]I2	++	++	++	++	0.31	−1.93	38.91	−1.36	0.18
Imipenem	+	+	+	+	−1.16	−0.97	139.0	−5.28	0.95

+ = not toxic; ++ = slightly toxic.

Table 8 Molinspiration property and Molinspiration bioactivity score data of the selected compounds and reference drugs.

Data	Pd(Dmtu)4]I2	Pd(Imt)4]I2	Pd(Metu)4]I2	Pd(Mpy)4]I2	Pd(Mpm)4]I2	Pd(Tmtu)4]I2	Pd(Tu)4]I2	Pd(Tna)4]I2	Imipenem
miLog P	1.65	−0.019	0.901	4.208	2.361	1.65	0.152	−2.073	−0.734
TPSA	48.108	48.108	76.1	31.582	57.366	48.108	104.092	77.83	113.715
natoms	15.0	15.0	13.0	17.0	17.0	15	11	21.0	20.0
MW	568.584	564.552	540.53	582.566	584.542	568.584	512.476	636.618	299.352
nON	4	4	4	2	4	4	4	4	7
nOHNH	4	4	6	2	2	4	8	4	4
Nviolations	1	1	2	1	1	1	2	1	0
Nrotb	4	0	2	0	0	4	0	2	7
Volume	279.297	258.576	243.947	276.231	267.919	279.297	208.597	320.25	255.433
GPCR L	−0.63	−0.47	−1.00	−0.26	−0.35	−0.63	−1.20	0.01	0.32
ICM	−0.25	−0.19	−0.51	0.07	−0.13	−0.25	−0.57	−0.08	−0.21
KI	−0.55	−0.62	−0.72	−0.20	−0.34	−0.55	−1.01	−0.04	−0.56
NRL	−0.81	−0.86	−1.34	−0.38	−0.53	−0.81	−0.45	−0.21	−0.21
PI	−0.70	−0.66	−0.81	−0.46	−0.55	−0.70	−1.01	−0.18	0.97
EI	−0.27	−0.23	−0.36	−0.08	−0.12	−0.27	−0.50	−0.04	1.00

GPCR L = GPCR ligand, ICM = ion channel modulator, KI = kinase inhibitor, NRL = nuclear receptor ligand, PI = protease inhibitor, EI = enzyme inhibitor.