**3. Results and discussion**

320 Antimicrobial Agents

+

b) Fig. 8. The synthesis of: a) esters (R2-*S,S*-eddba·2HCl); b) complexes [PtCl4(R2-*S,S*-eddba)]

The tested compounds were dissolved in DMSO and then diluted into nutrient liquid medium to achieve a concentration of 10%. Antibiotic, doxycycline (Galenika A.D., Belgrade), was

Antimicrobial activity of twenty-one palladium(II) and platinum(IV) complexes and their ligands was tested against 9 species of bacteria: 6 strains of pathogenic bacteria (including 4 standard strains: *Pseudomonas aeruginosa* ATCC 27853, *Enterococcus faecalis* ATCC 29212, *Staphylococcus aureus* ATCC 25923; *Sarcina lutea* ATCC 9341 and 2 clinical isolates: *Escherichia coli* and *Salmonella enterica*) and 3 species of probiotic bacteria (*Bacillus subtilis* IP 5832 PMFKG-P32, *Bifidobacterium animalis subsp. lactis* PMFKG-P33 and *Lactobacillus rhamnosus* PMFKG-P35 ). All clinical isolates were a generous gift from the Institute of Public Health, Kragujevac. The other microorganisms were provided from a collection held by the

Bacterial suspensions were prepared by the direct colony method. The colonies were taken directly from the plate and were suspended in 5 mL of sterile 0.85% saline. The turbidity of initial suspension was adjusted by comparing with 0.5 McFarland's standard (0.5 ml 1.17% w/v BaCl2×2H2O + 99.5 ml 1% w/v H2SO4) (Andrews, 2005). When adjusted to the turbidity of the 0.5 McFarland's standard, bacteria suspension contains about 108 colony forming unites (CFU)/mL. Ten-hold dilutions of initial suspension were additionally prepared into sterile 0.85% saline.

Antimicrobial activity was tested by determining the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) by using microdilution plate method

dissolved in nutrient liquid medium, a Mueller–Hinton broth (Torlak, Beograd).

Microbiology Laboratory Faculty of Science, University of Kragujevac.

K2PtCl6 Pt

LiOH

Cl

O

N N

O

O

R = ethyl (**C19**), propyl (**C20**), butyl (**C21**)

Cl Cl

R

R

Cl

O

O

RO

H

H

**2.2 In vitro antimicrobial assay** 

**2.2.1 Test substances** 

**2.2.2 Test microorganisms** 

**2.2.3 Suspension preparation** 

**2.2.4 Microdilution method** 

N+ OR

Cl <sup>H</sup> -

N+

Cl-

H

R = ethyl (**L19**), propyl (**L20**), butyl (**L21**)

O

The results of *in vitro* testing of antibacterial activities of the ligands and corresponding palladium(II) and platinum(IV) complex are shown in Table 1-10. For comparison, MIC and MBC values of doxycycline are listed in Table 11. The solvent (10% DMSO) did not inhibit the growth of the tested microorganisms.

The intensity of antimicrobial action varied depending on the species of microorganism and on the type and concentration of tested compounds. The difference between antimicrobial activity of the ligands and corresponding palladium(II) and platinum(IV) complexes is noticed and, in general, the most active were palladium(II) complexes.

The results of antibacterial testing for the ligands (**L1, L2, L3**) and corresponding palladium(II) complexes (**C1, C2, C3**) are shown in Table 1. The results for 3 strains of pathogenic bacteria and 2 species of probiotic bacteria were reported in the paper Vasić et al., (2010). Results for *S. enterica*, *Staphyl. aureus* ATCC 25923, *S. lutea* ATCC 9341 and *L. rhamnosus* were first presented in this paper. These ligands and complexes, being compared to positive control, showed low to moderate antibacterial activity. MIC and MBC values were in range from <7.81 to >1000 μg/mL, depending on the species of bacteria. Grampositive bacteria showed higher sensitivity. The most sensitive was *S. lutea* ATCC 9341, where MIC was for **C1** and **C2** <7.81 μg/mL. The best activity at Gram-negative bacteria was shown by **C2** to *P. aeruginosa* ATCC 27853 and *E. coli* (MIC was 31.25 μg/mL). The probiotics showed sensitivity similar to the sensitivity of the other bacteria to the tested compounds. Exception is *B. animalis subsp. lactis* where **L2**, **C2** and **L3** inhibited its growth at these concentrations: 7.81 μg/mL, 15,63 μg/mL and <7.81 μg/mL.

From Synthesis to Antibacterial

MIC, minimum inhibitory concentration (μg/mL),

MIC, minimum inhibitory concentration (μg/mL), MBC, minimum bactericidal concentration (μg/mL)

MIC, minimum inhibitory concentration (μg/mL), MBC, minimum bactericidal concentration (μg/mL)

2 Stanković et al., (2011a, 2011c)

MBC, minimum bactericidal concentration (μg/mL), nt, not tested

Activity of Some New Palladium(II) and Platinum(IV) Complexes 323

MIC MBC MIC MBC MIC MBC MIC MBC

MIC MBC MIC MBC MIC MBC MIC MBC

MIC MBC MIC MBC MIC MBC MIC MBC

Species L4 2 C4 L5 C5

*Escherichia coli* 500 1000 125 500 125 1000 125 500 *Salmonella enterica* 1000 >1000 1000 1000 >1000 >1000 1000 1000 *Pseud. aeruginosa* ATCC 27853 1000 1000 500 1000 >1000 >1000 500 1000 *Enter. faecalis* ATCC 29212 500 500 500 1000 >1000 >1000 500 >1000 *Staphyl. aureus* ATCC 25923 500 500 250 500 250 500 125 500 *Sarcina lutea* ATCC 9341 31.25 125 250 250 1000 1000 250 250 *Lactobacillus rhamnosus* 1000 1000 500 1000 nt nt 500 1000 *Bifidobact. animalis subsp. lactis* 250 500 125 1000 500 >1000 250 >1000 *Bacillus subtilis* IP 5832 125 500 15.63 >1000 62.5 >1000 7.81 1000

Table 2. Antibacterial activity of the ligands (**L4, L5**) and corresponding complexes (**C4, C5**).

Species L6 C6 L7 C7

*Escherichia coli* 15.63 500 31.25 500 15.63 125 <7.81 125 *Salmonella enterica* 1000 1000 250 500 1000 1000 1000 1000 *Pseud. aeruginosa* ATCC 27853 >1000 >1000 500 1000 500 >1000 500 1000 *Enter. faecalis* ATCC 29212 1000 >1000 500 1000 1000 >1000 500 1000 *Staphyl. aureus* ATCC 25923 31.25 125 125 125 31.25 125 500 500 *Sarcina lutea* ATCC 9341 31.25 31.25 31.25 31.25 <7.81 <7.81 250 250 *Lactobacillus rhamnosus* 31.25 250 62.50 125 62.50 250 500 1000 *Bifidobact. animalis subsp. lactis* 62.50 1000 62.50 1000 62.50 500 125 >1000 *Bacillus subtilis* IP 5832 250 >1000 500 1000 1000 >1000 500 >1000

Table 3. Antibacterial activity of the ligands (**L6, L7**) and corresponding complexes (**C6, C7**).

*Escherichia coli* 625 >1000 625 >1000 312.5 >1000 >1000 >1000 *Salmonella enterica* >1000 >1000 >1000 >1000 >1000 >1000 >1000 >1000 *Pseud. aeruginosa* ATCC 27853 >1000 >1000 >1000 >1000 >1000 >1000 >1000 >1000 *Enter. faecalis* ATCC 29212 >1000 >1000 >1000 >1000 >1000 >1000 625 >1000 *Staphyl. aureus* ATCC 25923 250 500 500 1000 31.25 125 250 500 *Sarcina lutea* ATCC 9341 250 250 500 500 <7.8 <7.8 250 250 *Lactobacillus rhamnosus* 1000 1000 500 1000 15.63 125 500 1000 *Bifidobact. animalis subsp. lactis* 78 >1000 78 >1000 >1000 >1000 >1000 >1000 *Bacillus subtilis* IP 5832 78.13 >1000 39.06 625 625 >1000 78 >1000

Table 4. Antibacterial activity of the ligands (**L8, L9**) and corresponding complexes (**C8, C9**).

Species L8 C8 L9 C9

The results of testing the ligands (**L4, L5, L6, L7**) and their palladium(II) complexes (**C4, C5, C6, C7**) are shown in Table 2 and Table 3. The results of testing for **L4** were reported in the paper by Stanković et al., (2011a; 2011c). The tested ligands, with few exceptions, show very low antimicrobial activity, while palladium(II) complexes show selective and moderate activity. Interestingly, **L6**, **L7** and **C6**, **C7** exhibit strong antibacterial activity towards *E. coli*, *Staphyl. aureus* ATCC 25923 and *S. lutea* ATCC 9341, MIC ranged <7.81 µg/mL to 31.25µg/mL. Probiotic bacteria showed high resistance to the effects of tested substances. The most sensitive was *B. subtilis* IP 5832 to **C5** and **C4** (MIC was 7.81µg/mL and 15.63 µg/mL).

The results of testing the ligands (**L8, L9, L10, L11**) and palladium(II) complexes (**C8, C9, C10, C11**) are shown in Table 4 and Table 5. The ligands and complexes, being compared to positive control, with few exceptions, showed low antibacterial activity. MIC and MBC values were in range from <7.8 to >1000 μg/mL, depending on the species of bacteria. **L9**, **L10** and **L11** showed excellent results to *S. lutea* ATCC 9341 (MIC and MBC <7.81 μg/mL) and **L10** and **L11** to *S. lutea* ATCC 9341, *Staphyl. aureus* ATCC 25923 and *L. rhamnosus* (MIC <7.81 μg/mL). In this case the ligands acted better than corresponding complexes and it is an exception. The complexes have weak antimicrobial activity and some better influence was seen on *B. subtilis* IP 5832 were MIC was in range from 39.06 to 312.5 μg/mL.

The results of testing the ligands (**L12, L13, L14, L15, L16**) and corresponding palladium (II) complexes (**C12, C13, C14, C15, C16**) are shown in Table 6 and Table 7. The results for these testing were accepted for publication in the paper by Radić et al., (2011b). All tested compounds demonstrated selective and moderate antibacterial activity. Tested ligands, with a few exceptions, show very low antimicrobial activity. The activity of corresponding complexes was higher than with the ligands. MICs values for ligands were in range from 250 µg/mL to >1000 µg/mL, and for complexes from 62.5 µg/mL to 1000 µg/mL. The Gram-positive bacteria were more sensitive than the Gram-negative bacteria especially by the activity of the complexes. The best effect was observed in **C16** to *S. lutea* ATCC 9341 were MIC and MBC 62.5 µg/mL. MICs for Gram-negative bacteria were at 500 μg/mL and 1000 μg/mL. The tested complexes (**C13**) and (**C14**) exhibited somewhat stronger antibacterial activity towards *P. aeruginosa* ATCC 27853 (MIC = 250 μg/mL). The probiotics showed sensitivity similar to the sensitivity of the other bacteria (Radić et al., 2011b).


MIC, minimum inhibitory concentration (μg/mL),

MBC, minimum bactericidal concentration (μg/mL), nt, not tested

Table 1. Antibacterial activity of the ligands (**L1,L2,L3**) and corresponding complexes (**C1, C2, C3**).

1 Vasić et al., (2010)

The results of testing the ligands (**L4, L5, L6, L7**) and their palladium(II) complexes (**C4, C5, C6, C7**) are shown in Table 2 and Table 3. The results of testing for **L4** were reported in the paper by Stanković et al., (2011a; 2011c). The tested ligands, with few exceptions, show very low antimicrobial activity, while palladium(II) complexes show selective and moderate activity. Interestingly, **L6**, **L7** and **C6**, **C7** exhibit strong antibacterial activity towards *E. coli*, *Staphyl. aureus* ATCC 25923 and *S. lutea* ATCC 9341, MIC ranged <7.81 µg/mL to 31.25µg/mL. Probiotic bacteria showed high resistance to the effects of tested substances. The most sensitive

The results of testing the ligands (**L8, L9, L10, L11**) and palladium(II) complexes (**C8, C9, C10, C11**) are shown in Table 4 and Table 5. The ligands and complexes, being compared to positive control, with few exceptions, showed low antibacterial activity. MIC and MBC values were in range from <7.8 to >1000 μg/mL, depending on the species of bacteria. **L9**, **L10** and **L11** showed excellent results to *S. lutea* ATCC 9341 (MIC and MBC <7.81 μg/mL) and **L10** and **L11** to *S. lutea* ATCC 9341, *Staphyl. aureus* ATCC 25923 and *L. rhamnosus* (MIC <7.81 μg/mL). In this case the ligands acted better than corresponding complexes and it is an exception. The complexes have weak antimicrobial activity and some better influence

The results of testing the ligands (**L12, L13, L14, L15, L16**) and corresponding palladium (II) complexes (**C12, C13, C14, C15, C16**) are shown in Table 6 and Table 7. The results for these testing were accepted for publication in the paper by Radić et al., (2011b). All tested compounds demonstrated selective and moderate antibacterial activity. Tested ligands, with a few exceptions, show very low antimicrobial activity. The activity of corresponding complexes was higher than with the ligands. MICs values for ligands were in range from 250 µg/mL to >1000 µg/mL, and for complexes from 62.5 µg/mL to 1000 µg/mL. The Gram-positive bacteria were more sensitive than the Gram-negative bacteria especially by the activity of the complexes. The best effect was observed in **C16** to *S. lutea* ATCC 9341 were MIC and MBC 62.5 µg/mL. MICs for Gram-negative bacteria were at 500 μg/mL and 1000 μg/mL. The tested complexes (**C13**) and (**C14**) exhibited somewhat stronger antibacterial activity towards *P. aeruginosa* ATCC 27853 (MIC = 250 μg/mL). The probiotics

was *B. subtilis* IP 5832 to **C5** and **C4** (MIC was 7.81µg/mL and 15.63 µg/mL).

was seen on *B. subtilis* IP 5832 were MIC was in range from 39.06 to 312.5 μg/mL.

showed sensitivity similar to the sensitivity of the other bacteria (Radić et al., 2011b).

Table 1. Antibacterial activity of the ligands (**L1,L2,L3**) and corresponding complexes

MIC, minimum inhibitory concentration (μg/mL),

(**C1, C2, C3**).

1 Vasić et al., (2010)

MBC, minimum bactericidal concentration (μg/mL), nt, not tested

Species L1 C1 L2 C2 L3 C3

*Escherichia coli* <sup>1</sup> 125 >500 62,5 125 31.3 >500 31,25 > 250 250 >500 125 > 500 *Salmonella enterica* >1000 >1000 125 125 nt nt 250 500 1000 >1000 250 500 *Pseud. aeruginosa* ATCC 27853 <sup>1</sup> >500 >500 125 250 >500 >500 31,25 125 250 >500 125 125 *Enter. faecalis* ATCC 29212 <sup>1</sup> >500 >500 125 250 125 >500 62,5 250 >500 >500 62,5 250 *Staphyl. aureus* ATCC 25923 >1000 >1000 62.5 125 nt nt 62.5 125 250 1000 62.5 125 *Sarcina lutea* ATCC 9341 1000 1000 <7.8 <7.8 nt nt <7.8 15,6 31,25 125 31,25 31,25 *Lactobacillus rhamnosus* nt nt 62.5 500 nt nt 62.5 250 nt nt 62.5 125 *Bifidobact. animalis subsp. lactis* <sup>1</sup> 125 >500 62,5 125 7.81 >500 15,6 125 <7.81 < 31.25 125 > 500 *Bacillus subtilis* IP 5832 <sup>1</sup> 125 >500 62,5 125 62.5 >500 15,6 125 62.5 >500 62,5 > 500

MIC MBC MIC MBC MIC MBC MIC MBC MIC MBC MIC MBC


MIC, minimum inhibitory concentration (μg/mL),

MBC, minimum bactericidal concentration (μg/mL), nt, not tested

Table 2. Antibacterial activity of the ligands (**L4, L5**) and corresponding complexes (**C4, C5**).


MIC, minimum inhibitory concentration (μg/mL), MBC, minimum bactericidal concentration (μg/mL)

Table 3. Antibacterial activity of the ligands (**L6, L7**) and corresponding complexes (**C6, C7**).


MIC, minimum inhibitory concentration (μg/mL), MBC, minimum bactericidal concentration (μg/mL)

Table 4. Antibacterial activity of the ligands (**L8, L9**) and corresponding complexes (**C8, C9**).

 2 Stanković et al., (2011a, 2011c)

From Synthesis to Antibacterial

MIC, minimum inhibitory concentration (μg/mL), MBC, minimum microbiocidal concentration (μg/mL)

MIC, minimum inhibitory concentration (μg/mL), MBC, minimum microbiocidal concentration (μg/mL)

and platinum(IV) (**C17b**) complexes.

*Pseud. aeruginosa ATCC* 

*Bifidobact. animalis subsp.* 

5 Radojević et al., (2011) 6 Stanković et al., (2011a; 2011c)

Activity of Some New Palladium(II) and Platinum(IV) Complexes 325

The results of *in vitro* testing of antibacterial activities of the ligand (**L17**) and corresponding

MIC MBC MIC MBC MIC MBC

palladium(II) (**C17a**) and platinum(IV) (**C17b**) complexes are shown in Table 8.

Species L17 C17a C17b

*Escherichia coli* >1000 >1000 250 500 >1000 >1000 *Salmonella enterica* >1000 >1000 250 500 >1000 >1000 *Pseud. aeruginosa ATCC 27853* 250 >1000 15.63 500 125 500 *Enter. faecalis ATCC 29212* 500 >1000 31.25 500 250 500 *Staphyl. aureus* ATCC 25923 500 >1000 31.25 500 250 500 *Sarcina lutea ATCC 9341* 500 >1000 62.5 500 125 500 *Lactobacillus rhamnosus* 125 >1000 62.5 >1000 31.25 >1000 *Bifidobact. animalis subsp. lactis* >1000 >1000 31.25 125 250 500 *Bacillus subtilis IP 5832* 500 >1000 250 500 250 500

Table 8. 5Antibacterial activity of the ligand (**L17**) and corresponding palladium(II) (**C17a**)

The best activity manifested palladium(II) complex **C17a** with also the best seen result on *P. aeruginosa* ATCC 27853 (MIC 15.63 μg/mL). The same one at Gram-positive bacteria had MIC 31.25 – 62.5 μg/mL. Platinum (IV) complex **C17b** has weaker activity and the best result manifested on *L. rhamnosus* where MIC was 31.25 μg/mL (Radojević et al., 2011).

MIC MBC MIC MBC MIC MBC MIC MBC

Species L4 C4a L18 C18

*Escherichia coli* 500 1000 1000 1000 >1000 >1000 >1000 >1000 *Salmonella enterica* 1000 >1000 1000 >1000 >1000 >1000 1000 >1000

*<sup>27853</sup>*1000 1000 1000 >1000 1000 >1000 1000 >1000 *Enter. faecalis ATCC 29212* 500 500 1000 1000 500 1000 1000 1000 *Staphyl. aureus* ATCC 25923 500 500 500 1000 500 500 1000 1000 *Sarcina lutea ATCC 9341* 31.25 125 31.25 62.5 62.5 125 31.25 62.5 *Lactobacillus rhamnosus* 1000 1000 1000 1000 1000 1000 1000 1000

*lactis* 250 500 500 1000 500 500 1000 >1000 *Bacillus subtilis IP 5832* 125 500 500 1000 500 500 500 1000

Table 9. 6Antibacterial activity of the ligands (**L4, L18**) and corresponding complexes (**C4a, C18**).

Antibacterial activity of the tested platinum(IV) (**C4a, C18**) complexes and corresponding ligands (**L4, L18**) are shown in Table 9. Results for these testing was reported in the papers Stanković et al., (2011a,c). The ligands and corresponding platinum(IV) complexes demonstrated low antimicrobial activity. There was no difference in activities between the


MIC, minimum inhibitory concentration (μg/mL), MBC, minimum bactericidal concentration (μg/mL)

Table 5. Antibacterial activity of the ligands (**L10, L11**) and corresponding complexes (**C10,C11**).


MIC, minimum inhibitory concentration (μg/mL), MBC, minimum bactericidal concentration (μg/mL)

Table 6. 3 Antibacterial activity of the ligands (**L12, L13, L14**) and corresponding complexes (**C12, C13, C14**).


MIC, minimum inhibitory concentration (μg/mL), MBC, minimum bactericidal concentration (μg/mL)

Table 7. 4 Antibacterial activity of the ligands (**L15, L16**) and corresponding complexes (**C15,C16**).

<sup>3</sup> Radić et al., (2011b)

<sup>4</sup> Radić et al., (2011b)

MIC MBC MIC MBC MIC MBC MIC MBC

MIC MBC MIC MBC MIC MBC MIC MBC MIC MBC MIC MBC

MIC MBC MIC MBC MIC MBC MIC MBC

Species L10 C10 L11 C11

MIC, minimum inhibitory concentration (μg/mL), MBC, minimum bactericidal concentration (μg/mL)

MIC, minimum inhibitory concentration (μg/mL), MBC, minimum bactericidal concentration (μg/mL)

MIC, minimum inhibitory concentration (μg/mL), MBC, minimum bactericidal concentration (μg/mL)

(**C12, C13, C14**).

3 Radić et al., (2011b) 4 Radić et al., (2011b)

*Escherichia coli* >1000 >1000 >1000 >1000 625 >1000 312.5 >1000 *Salmonella enterica* >1000 >1000 >1000 >1000 >1000 >1000 >1000 >1000 *Pseud. aeruginosa* ATCC 27853 >1000 >1000 >1000 >1000 >1000 >1000 312.5 >1000 *Enter. faecalis* ATCC 29212 156.3 >1000 625 >1000 >1000 >1000 156.3 >1000 *Staphyl. aureus* ATCC 25923 <7.8 125 31.25 125 <7.8 125 500 500 *Sarcina lutea* ATCC 9341 <7.8 <7.8 31.25 31.25 <7.8 <7.8 250 250 *Lactobacillus rhamnosus* <7.8 <7.8 31.25 62.5 <7.8 <7.8 500 1000 *Bifidobact. animalis subsp. lactis* >1000 >1000 >1000 >1000 >1000 >1000 625 >1000 *Bacillus subtilis* IP 5832 >1000 >1000 78 >1000 >1000 >1000 312.5 >1000

Table 5. Antibacterial activity of the ligands (**L10, L11**) and corresponding complexes (**C10,C11**).

Species L12 C12 L13 C13 L14 C14

*Escherichia coli* >1000 >1000 1000 1000 1000 >1000 500 500 1000 >1000 500 500 *Salmonella enterica* 1000 >1000 1000 1000 1000 >1000 500 500 1000 >1000 500 500 *Pseud. aeruginosa* ATCC 27853 500 >1000 500 1000 500 >1000 250 500 500 >1000 250 500 *Enter. faecalis* ATCC 29212 1000 1000 500 500 1000 1000 500 1000 500 1000 250 500 *Staphyl. aureus* ATCC 25923 500 1000 500 1000 1000 1000 500 1000 1000 1000 500 500 *Sarcina lutea* ATCC 9341 250 500 250 250 1000 1000 250 250 500 500 250 500 *Lactobacillus rhamnosus* >1000 >1000 1000 1000 1000 >1000 500 1000 1000 1000 500 500 *Bifidobact. animalis subsp. lactis* 500 500 500 1000 500 500 1000 1000 1000 1000 500 500 *Bacillus subtilis* IP 5832 500 500 500 500 500 500 500 500 1000 >1000 250 500

Table 6. 3 Antibacterial activity of the ligands (**L12, L13, L14**) and corresponding complexes

Species L15 C15 L16 C16

*Escherichia coli* 1000 >1000 500 500 >1000 >1000 1000 1000 *Salmonella enterica* 1000 >1000 500 1000 >1000 >1000 1000 1000 *Pseud. aeruginosa* ATCC 27853 500 >1000 500 1000 500 >1000 500 1000 *Enter. faecalis* ATCC 29212 500 1000 250 500 1000 1000 500 1000 *Staphyl. aureus* ATCC 25923 500 1000 500 500 >1000 >1000 500 500 *Sarcina lutea* ATCC 9341 250 250 500 500 1000 1000 62.5 62.5 *Lactobacillus rhamnosus* 1000 >1000 500 >1000 >1000 >1000 1000 1000 *Bifidobact. animalis subsp. lactis* 500 1000 250 500 1000 1000 500 1000 *Bacillus subtilis* IP 5832 500 500 250 250 1000 >1000 250 500

Table 7. 4 Antibacterial activity of the ligands (**L15, L16**) and corresponding complexes (**C15,C16**).


The results of *in vitro* testing of antibacterial activities of the ligand (**L17**) and corresponding palladium(II) (**C17a**) and platinum(IV) (**C17b**) complexes are shown in Table 8.

MIC, minimum inhibitory concentration (μg/mL),

MBC, minimum microbiocidal concentration (μg/mL)

Table 8. 5Antibacterial activity of the ligand (**L17**) and corresponding palladium(II) (**C17a**) and platinum(IV) (**C17b**) complexes.

The best activity manifested palladium(II) complex **C17a** with also the best seen result on *P. aeruginosa* ATCC 27853 (MIC 15.63 μg/mL). The same one at Gram-positive bacteria had MIC 31.25 – 62.5 μg/mL. Platinum (IV) complex **C17b** has weaker activity and the best result manifested on *L. rhamnosus* where MIC was 31.25 μg/mL (Radojević et al., 2011).


MIC, minimum inhibitory concentration (μg/mL), MBC, minimum microbiocidal concentration (μg/mL)

Table 9. 6Antibacterial activity of the ligands (**L4, L18**) and corresponding complexes (**C4a, C18**).

Antibacterial activity of the tested platinum(IV) (**C4a, C18**) complexes and corresponding ligands (**L4, L18**) are shown in Table 9. Results for these testing was reported in the papers Stanković et al., (2011a,c). The ligands and corresponding platinum(IV) complexes demonstrated low antimicrobial activity. There was no difference in activities between the

 5 Radojević et al., (2011)

<sup>6</sup> Stanković et al., (2011a; 2011c)

From Synthesis to Antibacterial

MIC, minimum inhibitory concentration (μg/mL), MBC, minimum microbiocidal concentration (μg/mL)

Table 11. Antibacterial activity of the positive control - doxycycline

with our research to a great extent (Radojević et al., 2010).

**4. Conclusion** 

toward tested compounds.

Activity of Some New Palladium(II) and Platinum(IV) Complexes 327

Species Doxycycline

*Escherichia coli* 7.81 15.625 *Salmonella enterica* 15.625 31.25 *Pseud. aeruginosa* ATCC 2785362.5 125 *Enter. faecalis* ATCC 29212 7.81 62.5 *Staphyl. aureus* ATCC 25923 0.224 3.75 *Sarcina lutea* ATCC 9341 < 0.448 7.81 *Lactobacillus rhamnosus* 7.81 31.25 *Bifidobact. animalis subsp. lactis* 31.25 62.5 *Bacillus subtilis IP 5832* 1.953 15.625

In general, the ligands demonstrated low and selective antimicrobial activity (with few exceptions) and the complexes showed selective and moderate antibacterial activity. MIC values were in range from <7.81μg/mL to >1000 μg/mL and MBC values from 15.625 μg/mL to >1000 μg/mL depending on the species of bacteria. The Gram-positive bacteria were more sensitive than the Gram-negative bacteria. The most sensitive species is *S. lutea* ATCC 9341. Tested probiotics, with a few exceptions, indicate high resistance toward tested compounds. *L. rhamnosus* shows the highest resistance among them*.* The tested complexes **C1**, **C2**, **C3** and **C17a** exhibit strong activity towards *E. coli*, *P. aeruginosa* ATCC 27853 and *E. faecalis* ATCC 29212. The **L6**, **L7** and **C6**, **C7** exhibit strong antibacterial activity towards *E. coli*. The tested compounds did not affect *S. enterica* or their activities were low. Some activity showed palladium(II) complexes (**C1, C2 , C3, C6** and **C17a**). At the ligands the most effective antimicrobial activity show **L6, L7, L9, L10** and **L11** while the most active complexes are **C1, C2, C3, C6** and **C17a.** For eleven ligands (**L1** - **L11**) and corresponding palladium(II) complexes (**C1** - **C11**) antifungal activity is investigated. Palladium(II) complexes showed good antifungal activity opposite to ligands. This study are in keeping

The intensity of antimicrobial action varied depending on the species of microorganism and on the type of tested compounds. The tested ligands, with few exceptions, show low antimicrobial activity. The difference between antimicrobial activity of the ligands and corresponding palladium(II) and platinum(IV) complexes is noticed and, in general, the most active were palladium(II) complexes. The Gram-positive bacteria were more sensitive than the Gram-negative bacteria. The most sensitive species is *Sarcina lutea* ATCC 9341 and the most resistant is *Salmonella enterica* where the tested compounds did not affect or their activities were low. Tested probiotics, with a few exceptions, also indicate high resistance

MIC MBC

ligands and corresponding complexes. The ligands and corresponding platinum(IV) complexes showed significant antibacterial activity against *S. lutea* ATTC 9341. MICs values were in range from 31.25 μg/mL to 62.5 μg/mL, and MBCs values were from 62.5 μg/mL to 125 μg/mL. The tested compounds did not affect the growth of Gram-negative bacteria or their activities were very low (MIC ranged from 500 μg/mL to >1000 μg/mL, MBC from 1000 μg/mL to >1000 μg/mL). Also, probiotic bacteria showed high resistance to the effects of tested substances. MICs were from 125 μg/mL to 1000 μg/mL, and MBCs were from 500 μg/mL to >1000 μg/mL (Stanković et al., 2011a,c).

The results of *in vitro* testing of antibacterial activities of the ligands (**L19, L20, L21**) and corresponding platinum(IV) (**C19, C20, C21**) complex are shown in Table 10.


MIC, minimum inhibitory concentration (μg/mL),

MBC, minimum microbiocidal concentration (μg/mL)

Table 10. Antibacterial activity of the ligands (**L19, L20, L21**) and corresponding complexes (**C19, C20, C21**).

The difference in action between ligands and corresponding complexes can be seen at Gram-positive bacteria. Ligands have significant antimicrobial effect on probiotic bacteria (**L20**, **L21**), and complexes on Gram-positive bacteria (**C19, C20, C21**). **C21** has better antimicrobial effect than two other complexes. The lowest antimicrobial action of compounds was on Gram-negative bacteria, where tested concentrations of ligands almost didn't have the influence, while corresponding complexes had some better action, but still weak and limited. *L. rhamnosus* also showed similar resistance to the action of tested compounds (none of the tested concentrations had the influence on its growth), while the other probiotic bacteria were more sensitive, especially to the action of ligands, where MIC goes from <31.25 µg/mL to 250 µg/mL. At complexes MIC is in the range from125 µg/mL to 1000 µg/mL.

The gram-positive bacteria were more sensitive than the gram-negative bacteria. The platinum(IV) complexes showed high antibacterial activity against Gram-positive bacteria. MIC values were in range from 7.81 μg/mL to 1000 μg/mL, and MBC values were from 15.63 μg/mL to 1000 μg/mL depending on the species of bacteria. The most sensitive was *S. lutea* ATCC 9341 (MIC values are 7.81 μg/mL, 15.625 μg/mL and 31.25 μg/mL for different complexes.

ligands and corresponding complexes. The ligands and corresponding platinum(IV) complexes showed significant antibacterial activity against *S. lutea* ATTC 9341. MICs values were in range from 31.25 μg/mL to 62.5 μg/mL, and MBCs values were from 62.5 μg/mL to 125 μg/mL. The tested compounds did not affect the growth of Gram-negative bacteria or their activities were very low (MIC ranged from 500 μg/mL to >1000 μg/mL, MBC from 1000 μg/mL to >1000 μg/mL). Also, probiotic bacteria showed high resistance to the effects of tested substances. MICs were from 125 μg/mL to 1000 μg/mL, and MBCs were from

The results of *in vitro* testing of antibacterial activities of the ligands (**L19, L20, L21**) and

Species L19 C19 L20 C20 L21 C21

*Escherichia coli* >1000 >1000 1000 >1000 >1000 >1000 1000 1000 >1000 >1000 1000 1000 *Salmonella enterica* >1000 >1000 >1000 >1000 >1000 >1000 1000 1000 >1000 >1000 1000 1000 *Pseud. aeruginosa* ATCC 27853 >1000 >1000 1000 >1000 >1000 >1000 1000 >1000 >1000 >1000 1000 >1000 *Enter. faecalis* ATCC 29212 1000 >1000 1000 1000 1000 >1000 250 500 1000 1000 125 500 *Staphyl. aureus* ATCC 25923 1000 >1000 500 1000 1000 >1000 250 250 1000 >1000 125 250 *Sarcina lutea* ATCC 9341 1000 >1000 7.81 15.625 1000 >1000 15.625 31.25 1000 >1000 31.25 62.5 *Lactobacillus rhamnosus* >1000 >1000 >1000 >1000 >1000 >1000 >1000 >1000 >1000 >1000 >1000 >1000 *Bifidobact. animalis subsp. lactis* 125 250 1000 1000 <31.25 125 500 500 <31.25 250 125 500 *Bacillus subtilis IP 5832* 125 250 250 1000 250 250 250 250 250 250 125 250

Table 10. Antibacterial activity of the ligands (**L19, L20, L21**) and corresponding complexes

The difference in action between ligands and corresponding complexes can be seen at Gram-positive bacteria. Ligands have significant antimicrobial effect on probiotic bacteria (**L20**, **L21**), and complexes on Gram-positive bacteria (**C19, C20, C21**). **C21** has better antimicrobial effect than two other complexes. The lowest antimicrobial action of compounds was on Gram-negative bacteria, where tested concentrations of ligands almost didn't have the influence, while corresponding complexes had some better action, but still weak and limited. *L. rhamnosus* also showed similar resistance to the action of tested compounds (none of the tested concentrations had the influence on its growth), while the other probiotic bacteria were more sensitive, especially to the action of ligands, where MIC goes from <31.25 µg/mL to 250 µg/mL. At complexes MIC is in the range

The gram-positive bacteria were more sensitive than the gram-negative bacteria. The platinum(IV) complexes showed high antibacterial activity against Gram-positive bacteria. MIC values were in range from 7.81 μg/mL to 1000 μg/mL, and MBC values were from 15.63 μg/mL to 1000 μg/mL depending on the species of bacteria. The most sensitive was *S. lutea* ATCC 9341 (MIC values are 7.81 μg/mL, 15.625 μg/mL and 31.25 μg/mL for different

MIC MBC MIC MBC MIC MBC MIC MBC MIC MBC MIC MBC

corresponding platinum(IV) (**C19, C20, C21**) complex are shown in Table 10.

500 μg/mL to >1000 μg/mL (Stanković et al., 2011a,c).

MIC, minimum inhibitory concentration (μg/mL), MBC, minimum microbiocidal concentration (μg/mL)

from125 µg/mL to 1000 µg/mL.

(**C19, C20, C21**).

complexes.


MIC, minimum inhibitory concentration (μg/mL), MBC, minimum microbiocidal concentration (μg/mL)

Table 11. Antibacterial activity of the positive control - doxycycline

In general, the ligands demonstrated low and selective antimicrobial activity (with few exceptions) and the complexes showed selective and moderate antibacterial activity. MIC values were in range from <7.81μg/mL to >1000 μg/mL and MBC values from 15.625 μg/mL to >1000 μg/mL depending on the species of bacteria. The Gram-positive bacteria were more sensitive than the Gram-negative bacteria. The most sensitive species is *S. lutea* ATCC 9341. Tested probiotics, with a few exceptions, indicate high resistance toward tested compounds. *L. rhamnosus* shows the highest resistance among them*.* The tested complexes **C1**, **C2**, **C3** and **C17a** exhibit strong activity towards *E. coli*, *P. aeruginosa* ATCC 27853 and *E. faecalis* ATCC 29212. The **L6**, **L7** and **C6**, **C7** exhibit strong antibacterial activity towards *E. coli*. The tested compounds did not affect *S. enterica* or their activities were low. Some activity showed palladium(II) complexes (**C1, C2 , C3, C6** and **C17a**). At the ligands the most effective antimicrobial activity show **L6, L7, L9, L10** and **L11** while the most active complexes are **C1, C2, C3, C6** and **C17a.** For eleven ligands (**L1** - **L11**) and corresponding palladium(II) complexes (**C1** - **C11**) antifungal activity is investigated. Palladium(II) complexes showed good antifungal activity opposite to ligands. This study are in keeping with our research to a great extent (Radojević et al., 2010).

### **4. Conclusion**

The intensity of antimicrobial action varied depending on the species of microorganism and on the type of tested compounds. The tested ligands, with few exceptions, show low antimicrobial activity. The difference between antimicrobial activity of the ligands and corresponding palladium(II) and platinum(IV) complexes is noticed and, in general, the most active were palladium(II) complexes. The Gram-positive bacteria were more sensitive than the Gram-negative bacteria. The most sensitive species is *Sarcina lutea* ATCC 9341 and the most resistant is *Salmonella enterica* where the tested compounds did not affect or their activities were low. Tested probiotics, with a few exceptions, also indicate high resistance toward tested compounds.

From Synthesis to Antibacterial

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**16** 

*Iran* 

**Antibacterial Agents in Dental Treatments** 

*Faculty of Dentistry, Tabriz University of Medical Sciences,Tabriz,* 

*Faculty of Dentistry, Tabriz University of Medical Sciences,Tabriz,* 

*1Dental and Periodontal Research Center,* 

*2Department of Endodontics,* 

Saeed Rahimi1, Amin Salem Milani1, Negin Ghasemi2,\* and Shahriar Shahi1

Because progressive increase in serious transmissible diseases over the last few decades, every health care specialty that involves contact with mucosa, blood or blood contamination, like dentistry, should regulate regarding sterilization and disinfection. Dental patients and dental health-care workers may be exposed to a variety of microorganisms via blood or oral or respiratory secretions. These microorganisms may include cytomegalovirus, *hepatitis B virus (HBV), hepatitis C virus (HCV), herpes simplex virus types 1* and *2, human immunodeficiency virus (HIV), Mycobacterium tuberculosis, staphylococci, streptococci*, and other viruses and bacteria; specifically, those that infect the upper respiratory tract (Blently, 1994). Infections may be transmitted in the dental operatory through several routes, including direct contact with blood, oral fluids or other secretions; indirect contact with contaminated instruments, operatory equipment or environmental surfaces or contact with airborne contaminants present in either droplet spatter or aerosols of oral and respiratory fluids. Infection via any of these routes requires that all three of the following conditions be present (commonly referred to as "the chain of infection": a susceptible host; a pathogen with sufficient infectivity, numbers to cause infection and a portal through which the pathogen may enter the host) (Burkhart, 1970). Effective infectioncontrol strategies are intended to break one or more of these "links" in the chain, thereby preventing infection. A set of infection-control strategies common to all health-care delivery settings should reduce the risk of transmission of infectious diseases caused by blood-borne pathogens such as *HBV* and *HIV*. Because all infected patients cannot be identified by medical history, physical examination, or laboratory tests, it is recommended that blood and body fluid precautions be used consistently for all patients. In dentistry, beside personal protections like eyewear, gloves and gowns, pretreatment mouth rinse, rubber dam and high velocity air evacuation are the other considerations regarding infection control (Hackney, 1989). Suitable sterilization and disinfection of instruments are inseparable parts of infection control puzzle. So, discussion about the techniques and agents used in sterilization and disinfection is very important, nowadays. In this chapter we mention the

antibacterial agents used in sterilization and disinfection in dentistry.

**1. Introduction** 

 \*

Corresponding Author

Vujić, J.M., Garcia-Granda, S., Menendez-Taboada, L. & Trifunović, S.R. (2011). Crystal structure of palladium(II) complex with *O,O'*- dipentil-etilenediamine- *N,N'*-di- (*S,S*)-2(4-methy)-pentanoate ligand. *Proceedings of XVIII Conference of the Serbian Crystallographic Society*, pp. 40, ISBN: 978-86-7031-194-7, Fruška Gora, Serbia, June 2-4, 2011.
